전체메뉴
Article Search

PNF Preventive Nutrition and Food Science

Open Access


ISSN 2287-8602
QR Code QR Code

Review

Article

Review

Prev Nutr Food Sci 2024; 29(3): 237-255

Published online September 30, 2024 https://doi.org/10.3746/pnf.2024.29.3.237

Copyright © The Korean Society of Food Science and Nutrition.

The Efficacy of Probiotics Supplementation on the Quality of Life of Patients with Gastrointestinal Disease: A Systematic Review of Clinical Studies

Jalal Moludi1,3 , Amir Saber1,3 , Morteza Arab Zozani2 , Shima Moradi3 , Yasaman Azamian3 , Salimeh Hajiahmadi4 , Yahya Pasdar1 , Fardin Moradi3

1Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology and 3Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6719851552, Iran
2Social Determinants of Health Research Center (SDHRC), School of Health, Birjand University of Medical Sciences, Birjand 32048321, Iran
4Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd 8915173160, Iran

Correspondence to:Amir Saber, E-mail: dr.saber61@gmail.com

Received: April 15, 2024; Revised: June 16, 2024; Accepted: June 24, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Patients with gastrointestinal (GI) disorders might benefit from probiotic supplementation to resolve their bowel symptoms and enhance their quality of life (QoL). This systematic review aimed to evaluate the effects of oral probiotic supplementation on improving QoL. Relevant studies were systematically searched in online databases, including PubMed, Scopus, Embase, ProQuest, and Google Scholar up to September 2022 using relevant keywords. Studies that were conducted on GI patients and presented QoL outcomes were included. The Revised Cochrane Risk of Bias 2 tool and the Risk Of Bias In Non-randomized Studies of Intervention tool were used to assess the risk of bias. Of the 4,555 results found in the systematic search of databases, only 36 studies were eligible for evaluation. According to this systematic review, 24 studies reported improvements, whereas 12 studies reported no improvements on QoL in GI patients supplemented with probiotics. We found that probiotics may improve the QoL of patients with GI diseases and related metabolic complications. Therefore, probiotics can be a useful supportive treatment strategy in these patients.

Keywords: gastrointestinal diseases, probiotics, quality of life

INTRODUCTION

Functional gastrointestinal disorders (FGIDs) are characterized by a combination of motility issues; visceral hypersensitivity; and changes in mucosal and immune function, gut microbiota, and central nervous system (CNS) processing (Drossman, 2016). Despite being poorly understood because of their complex pathophysiology, FGIDs [including irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation (FC)] account for approximately 33% of all appointments at gastroenterology clinics (Shivaji and Ford, 2014). According to previous studies, more than 66% of individuals suffering from FGIDs have consulted a healthcare professional within the past year, 40% rely on medications regularly, and 33% have undergone unwarranted abdominal surgeries including hysterectomies or cholecystectomies to relieve their symptoms (Jafari et al., 2018). Aside from being costly to manage, these conditions also affect patients’ quality of life (QoL), which emphasize their fundamental importance to healthcare systems and society (Jafari et al., 2018). According to previous studies, pathogenic gut microbiota may be responsible for various chronic GI disorders, including cancer and diseases involving inflammation, metabolic, cardiovascular, autoimmune, neurologic, and psychiatric components (Kataoka, 2016; Lynch and Pedersen, 2016; Cani, 2017). The human body harbors the most abundant microorganisms in the GI tract. Therefore, intestinal microflora changes have been observed as a leading mechanism in the occurrence of some GI diseases (Aziz et al., 2013; Guinane and Cotter, 2013).

Probiotics are live microorganisms found in food and dietary supplements that, when consumed, can enhance the host’s health and provide nutritional value (Fuller and Gibson, 1998). These microorganisms mostly comprise bacteria and yeasts and naturally exist in fermented foods or some functional food products (Lin, 2003). The most well-known genera of probiotics belong to Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus. These microorganisms exhibit different health effects based on the species and gender of the host (Marteau et al., 1993). Koretz demonstrated that various factors, including species, dosage, host’s immune system, underlying pathology, and treatment duration, influence the efficacy of probiotics in the human microbiota (Koretz, 2018). Recently, many clinical trials have used different forms of probiotics to therapeutically modulate the intestinal microbiome in adults (Fuller and Gibson, 1998; Ferrario et al., 2014; Irwin et al., 2018). Because of their effectiveness in preventing and treating GI disorders, probiotics are being increasingly used in various foods or supplements to improve the microbiome (Fuller and Gibson, 1998; McFarland, 2006; McFarland and Dublin, 2008; Hoveyda et al., 2009). Moreover, several probiotic species have been used in a targeted and specific way for the prevention and treatment of specific diseases and have generally shown positive effects (Ritchie and Romanuk, 2012; Waitzberg et al., 2015; Miller et al., 2016).

In this regard, using some probiotic species can lead to a QoL improvement (Hungin et al., 2013). Research conducted in laboratory and live animal settings has demonstrated that probiotics can effectively diminish bloating, pain, and abdominal symptoms in individuals suffering from IBS (Kim et al., 2003; Aragon et al., 2010; Wong et al., 2015; Staudacher et al., 2017). In addition, studies on adults and children demonstrate the favorable effect of probiotic treatment on stool frequency, stool consistency, and constipation (Chmielewska and Szajewska, 2010). In another study, the administration of probiotics and synbiotics after surgery decreased the incidence of complications and enhanced the QoL and longevity of patients with colorectal cancer (Amitay et al., 2020). While many studies have investigated how probiotics can affect the QoL of individuals with GI diseases, no comprehensive systematic review has been conducted to reveal the potential complementary role of probiotics in patients with GI diseases and to identify existing scientific gaps. Therefore, based on available evidence, the present study investigated whether probiotic supplementation can improve the QoL of most GI patients by improving symptoms.

METHODS

This systematic review was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Furthermore, the study protocol was registered in the International Prospective Register of Systematic Reviews hosted by the Center for Reviews and Dissemination (PROSPERO) (CRD42022382414).

Search strategy

Two researchers conducted a thorough systematic search in five online databases (i.e., PubMed, Scopus, Embase, ProQuest, and Google Scholar) to identify relevant studies. The keywords were carefully selected, and pre-established criteria were used for included studies. The following Medical Subject Headings (MeSH) were applied in certain combinations: “probiotics,” “quality of life,” “probiotics and quality of life,” “probiotics and GI microbiome,” “probiotics and GI disease,” “probiotics and irritable bowel syndrome,” “probiotics and health-related outcomes,” and Medical Outcomes Study Short Form 36-Item questionnaire (SF-36).

Inclusion and exclusion criteria

Two researchers independently screened the titles and abstracts in the online database based on the inclusion and exclusion criteria. Eligible studies were required to meet the following inclusion criteria: 1) English-language articles available online (up to September 2022); 2) primary research articles and studies conducted on human individuals; and 3) all clinical trial studies on the effect of probiotics on the QoL in GI patients. Meanwhile, letters, comments, short communications, abstracts, studies on pregnant and lactating women, and in vitro and animal research were excluded. Additionally, all bibliographies of pertinent studies were examined to identify potentially relevant studies. After the search was completed, duplicate citations were removed.

Screening and data extraction

Two investigators independently reviewed eligible full text studies. Thereafter, data extraction was conducted using standardized forms and research questions. In case of disputes, a third researcher assessed the precision and quality of the inputted data. Next, variables including general manuscript details (author, country, location, and year), subject characteristics (age, clinical setting or population), study design and intervention characteristics (study quality, study design, sample size, QoL assessment method, probiotic strain, daily dosage, and treatment duration), and QoL summary statistics necessary for systematic review were recorded in a predetermined database. Initially, 94 studies were selected in the comprehensive search. The titles and abstracts of studies were reviewed to exclude papers published in non-English journals (six studies were excluded). Afterward, review articles, study protocols, commentaries, and case reports were removed (11 studies were excluded). Next, the full text of the remaining studies was examined and reviewed. Studies that failed to describe the QoL or those that were non-randomized, non-controlled, or otherwise irrelevant were further removed (four studies were excluded). Finally, studies on the population with GI diseases were isolated, and 36 studies were eligible for the final review (Fig. 1).

Figure 1. Flow chart of the study selection process.

Quality assessment

The Cochrane Collaboration’s tools were used to identify potential sources of bias in the selected studies. Two authors independently assessed each included study using the Revised Cochrane Risk of Bias 2 (RoB2) tool and the Risk Of Bias In Non-randomized Studies of Intervention (ROBINS-I) tool (Higgins et al., 2011). The methodological domains assessed for parallel and cross-over randomized controlled trials (RCTs) included the randomization process, deviation from intended interventions, missing outcome data, outcome measurement, and selection of reported results. Bias was evaluated as judgment for every criterion (indicated as “high risk of bias,” “low risk of bias,” or “some concerns”). Meanwhile, the methodological domains assessed for non-randomized clinical trials included bias from confounding, bias in participant selection, bias in intervention classification, bias from deviations in interventions, bias from missing data, bias in outcome measurement, and bias in the selection of reported results. Differences between these procedures were settled via agreement or seeking input from a third party, following communication with the authors of the original study for further explanation. If the trials did not provide sufficient information for assessment, we contacted the authors via email and allowed them a period of at least four weeks to reply.

RESULTS

Study selection

After applying all exclusion criteria, the final review was limited to 36 studies. Sixteen studies were related to IBS (Drisko et al., 2006; Choi et al., 2011; Dapoigny et al., 2012; Cappello et al., 2013; Abbas et al., 2014; Lorenzo-Zúñiga et al., 2014; Choi et al., 2015; Šmid et al., 2016; Giannetti et al., 2017; Nobutani et al., 2017; Pinto-Sanchez et al., 2017; Preston et al., 2018; Aroniadis et al., 2019; Catinean et al., 2019; Francavilla et al., 2019; El-Salhy et al., 2020). Eight studies were related to constipation (Ding et al., 2016; Cudmore et al., 2017; Ibarra et al., 2018; Xinias et al., 2018; Dimidi et al., 2019; Kommers et al., 2019; Riezzo et al., 2019; Olgac et al., 2020). Five studies were related to rectal cancer (Ohigashi et al., 2011; Lee et al., 2014; Theodoropoulos et al., 2016; Golkhalkhali et al., 2018; Radvar et al., 2020). One study was related to cirrhosis (Macnaughtan et al., 2020). One study was related to non-celiac gluten sensitivity disease (Di Pierro et al., 2020). One study was related to infant colic (Ahmadipour et al., 2020). One study was related to gastric bypass surgery (Chen et al., 2016). Two studies were related to FGIDs (Ringel-Kulka et al., 2011; Gomi et al., 2018). One study was related to ulcerative colitis (Fujimori et al., 2009). The details of each study are summarized in Tables 15.

Table 1 . IBS-related disease: characteristics of selected clinical trials included in the review.

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
El-Salhy et al., 2020 (Norway)RCTIBS16539.9±9.030 g FMT or 60 g FMT at a ratio of 1:1:1 The material for FMTFMT3 monthsIBS-QoLPositive effect
Catinean et al., 2019 (Romania)RCTIBS9018-75
G1=38.77±10.96
G2=39.07±16.00
G3=40.37±11.95
G2=7 days: 1 cap
27 days: 2 cap
G1=Bifidobacterium longum W11
G2=five Bacillus spp.
34 days
G1 and G3=10+24
G2=34
IBS-QoL (SF-36)Positive effect
Preston et al., 2018 (USA)RCTIBS86Plac: 39.9
Int: 40.6
2 capsules
50×109 CFU
Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR212 weeksIBS-QoLPositive effect
Giannetti et al., 2017 (Italy)RCTChildren with IBS and functional dyspepsia738.0-17.93 billion (3×109) of Bifidobacterium longum BB536, 1 billion (1×109) of B. infantis M-63, 1 billion (1×109) of B. breve M-16V3 Bifidobacteria:M-63breve M-16Vlongum BB53616 weeks:
2-week run-in phase
6 weeks Int
2-week “washout”
Afterward, each patient was switched to the other group
6 weeks Int
FDIPositive effect
Pinto-Sanchez et al., 2017 (Canada)RCTIBS44Int: 46.5 (30-58)
Plac: 40.0 (26-57)
1.0E+10Bifidobacterium longum NCC3001 (BL)6-week treatment
10 week follow-up
SF-36Positive effect
Nobutani et al., 2017 (Japan)RCTIBS30Int: 52.6±20.1
Plac: 45.9±19.5
13×108 CFULactobacillus gasseri CP23054 weeksIBS-QoL and PSQI-JPositive effect
Choi et al., 2015 (Korea)RCTNon-diarrheal-type IBS28520-73 (47)Group 1: 1.0×1010
CFU
Groups 2 and 3: 1.5×1010
Group 4: 3×1010
Bacillus subtilis and Streptococcus faecium4 weeksIBS-QoLPositive effect
Abbas et al., 2014 (Pakistan)RCTIBS-D72
64
(completed)
18-60
Int:
37.7±11.6
Plac:
33.0±12.0
750 mg/dSaccharomyces boulardii2-week run-in
6 weeks Int
IBS-QoLPositive effect
Lorenzo-Zúñiga et al., 2014 (Spain)RCTIBS7320-70
Int: 47.5±13.1
46.3±11.6
Plac: 46.5±13.1
1-3×1010 CFU or 3-6×109Two Lactobacillus plantarum (CECT7484 and CECT7485) and one Pediococcus acidilactici (CECT7483)6 weeksIBS-QoLPositive effect
Cappello et al., 2013 (Italy)RCTIBS6438.7±12.65×109 Lactobacillus plantarum, 2×109 L. casei subp. rhamnosus and 2×109 L. gasseri, 1×109 Bifidobacterium infantis and 1×109 B. longum, 1×109 L. acidophilus, 1×109 L. salivarius and 1×109 L. sporogenes and 5×109 Streptococcus thermophilus
Prebiotic inulin 2.2 g
Lyophilized bacteria: L. plantarumL. casei subp. rhamnosusL. gasseriBifidobacterium infantisL. acidophilusL. salivariusL. sporogenesStreptococcus thermophilus
Prebiotic inulin
6 weeks
(2-week run-in and 4-week treatment)
SF-36Positive effect
Choi et al., 2011 (Korea)RCTIBS6741±132×1011Saccharomyces boulardii4 weeksIBS-QoLPositive effect
Drisko et al., 2006 (USA)Open-label pilot study
Prospective outcome study
IBS2024-8110 billion CFULactobacillus acidophilus, Bifidobacterium bifidum, L. rhamnosus, L. plantarum, B. infantis, L. salivarius, L. bulgaricus, L. casei, L. brevis, and Streptococcus thermophilus1 yearIBS-QoLPositive effect

RCT, randomized control trial; IBS, irritable bowel syndrome; FMT, fecal microbiota transplantation; QoL, quality of life; IBS-QoL, irritable bowel syndrome QoL; IBS-D, diarrhea-dominant irritable bowel syndrome; SF-36, 36-item short form survey; CFU, colony forming unit; FDI, Functional Disability Inventory; Int, intervention; Plac, placebo; PSQI-J, Pittsburgh Sleep Quality Index..



Table 2 . Constipation-related disease: characteristics of selected clinical trials included in the review.

ReferenceType of studyClinical setting/populationSample sizeAgeDaily doseProbiotic speciesDuration of interventionSystemMain outcomes
Olgac et al., 2020 (Turkey)RCTChildren with FC494-16 years1×108 CFULactobacillus reuteri DSM 17938 or lactulose4 weeksKINDL HRQOLPositive effect
Kommers et al., 2019 (Brazil)RCTFemale university students with intestinal constipation6320-40 years
Int: 27.15±5.52
Plac: 24.38±5.41
109 CFU of each oneBifidobacterium lactis (BL04), B. bifidum (Bb-06), Lactobacillus acidophilus (La-14), L. casei (Lc-11), Lactococcus lactis (LL-23)45 daysPAC-QoLPositive effect
Xinias et al., 2018 (Greece)Non-randomized clinical trialInfants with FC653-13 weeks
Int: 1.4±0.8
Plac: 1.7±0.9
Not reportedBifidobacterium lactis BB121 monthNot reported (parents completed a QoL)Positive effect
Cudmore et al., 2017 (Ireland)RCTChronic, FC6918-80 years6×108 CFU twice dailyLactobacillus rhamnosus PXN 54 (NCIMB 30188), Bifidobacterium bifidum PXN 23 (NCIMB 30179), L. acidophilus PXN 35 (NCIMB 30184), L. plantarum PXN 47 (NCIMB 30187), and L. bulgaricus PXN 39 (NCIMB 30186)
Also psyllium and inulin
4 weeksPAC-QoLPositive effect

RCT, randomized control trial; FC, functional constipation; CFU, colony forming unit; QoL, quality of life; KINDL HRQOL, KINDL Health-Related QoL; PAC-QoL, Patient Assessment of Constipation QoL..



Table 3 . Functional gastrointestinal disorders (FGIDs): characteristics of selected clinical trials included in the review.

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of intervention (weeks)SystemMain outcomes
Ringel-Kulka et al., 2011 (USA)RCTFunctional bowel disorders6018-65 Mean age Int: 36 Plac: 37Twice a day (2×1011 CFU CFU/d)Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07)8IBS-QoLPositive effect

RCT, randomized control trial; CFU, colony forming unit; IBS-QoL, irritable bowel syndrome-quality of life; Int, intervention; Plac, placebo..



Table 4 . Colorectal cancer-related disease: characteristics of selected clinical trials included in the review.

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Radvar et al., 2020 (Iran)RCTRectal cancer38Int: 57.58±12.78 Plac: 62.89±13.932 times a day 1×108 CFU/gLactobacillus casei PXN 37, L. rhamnosus PXN 54, Streptococcus thermophilus 81 PXN 66, Bifidobacterium breve PXN 25, L. acidophilus PXN 35, B. longum PXN 30, L. bulgaricus PXN 39, FOS (fructooligosaccharide), magnesium stearate (source: mineral and vegetable), and vegetable capsule (hydroxypropyl methyl cellulose)6 weeksEORTC QLQ-C30Positive effect
Golkhalkhali et al., 2018 (Malaysia)RCTColorectal cancer140<18Two sachets daily 30 billion (CFUs) per sachetLactobacillus acidophilus BCMCR 12130, L. casei BCMCR 12313, Lactobacillus lactis BCMCR 12451, Bifidobacterium bifidum BCMCR 02290, B. longum BCMCR 02120, and B. infantis BCMCR 021298 weeksEORTC QLQ-C30Positive effect
Lee et al., 2014 (Korea)RCTColorectal cancer6056.18±8.86Twice a day 2×109 CFULacidofil (Lactobacillus rhamnosus R0011 andL. acidophilus R0052)12 weeksFACTPositive effect
Ohigashi et al., 2011 (Japan)Questionnaire-based studyColorectal cancer6363±910 mg of Bacillus natto and 30 mg of Lactobacillus acidophilusB. natto and L. acidophilus3 monthsSF-36 and EORTC QLQ-C30Positive effect

RCT, randomized control trial; Int, intervention; Plac, placebo; CFU, colony forming unit; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30; FACT, Functional Assessment of Cancer Therapy; SF-36, 36-item short form survey..



Table 5 . Other diseases: characteristics of selected clinical trials included in the review.

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Di Pierro et al., 2020 (Italy)Non-randomized clinical trialNon-celiac gluten sensitivity30Int: 46.87±17.06 Plac: 43.53±18.941 dose/day 1×109 CFU (1 billion)Bifidobacterium longum ES1 or GFD3 monthsDocument of scientific support to the protocol for the diagnosis and follow-up of celiac diseasePositive effect
Chen et al., 2016 (Taiwan)RCTGastric bypass surgery5318-60 35.1±8.3Twice daily A: 5×109 CFU (5 billion) B: 8×109 CFU (8 billion)A: 1 g Clostridium butyricum MIYAIRI B: 300 mg Bifidobacterium longum BB5362 weeksmGIQLPositive effect
Fujimori et al., 2009 (Japan)RCTUlcerative colitis83Pro=36±16 Pre=37±13 Syn=35±102×109 CFUBifidobacterium longum Also prebiotic (psyllium) and synbiotic4 weeksIBDQPositive effect

RCT, randomized control trial; Int, intervention; Plac, placebo; Pro, probiotics; Pre, prebiotics; Syn, symbiotic; CFU, colony forming unit; GFD, gluten-free diet; mGIQL, modified Gastrointestinal QoL Index; IBDQ, Inflammatory Bowel Disease Questionnaire..



Quality assessment

The risk of bias of included studies is presented in Table 6 and 7. Out of the 32 parallel and cross-over double-blind RCTs that were included, only 14 studies had low risk of bias. The rest revealed some concerns and high risk in overall risk of bias (Table 7). Furthermore, each of the four non-randomized clinical trials showed a significant potential for bias. Confounding bias was the major concern in non-randomized clinical trials (Table 8).

Table 6 . Characteristics of included studies that did not find any effect.

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Francavilla et al., 2019 (Italy)RCTPatients with celiac disease and IBS109Age 18 years and above
Int: 43.3 (18.8-62.2)
Plac: 44.6 (19.3-63.4)
5×109 CFU/sachet+5×109 CFU/sachet+10×109 CFU/sachet+10×109 CFU/sachet+10×109 CFU/sachetLactobacillus casei LMG 101/37 P-17504 (5×109 CFU/sachet), L. plantarum CECT 4528 (5×109 CFU/sachet), Bifidobacterium animalis subsp. lactis Bi1 LMG P-17502 (10×109 CFU/sachet), B. breve Bbr8 LMG P-17501 (10×109 CFU/sachet), B. breve Bl10 LMG P-17500 (10×109 CFU/sachet)14 weeksIBS–QoLWithout effect
Aroniadis et al., 2019 (USA)RCTIBS4518-65
Int: 33 (27-48)
Plac: 42 (28-48)
25 capsules perday
0.38 g minimally
Processed donor whole stool per capsule12 weeksIBS–QoLWithout effect
Šmid et al., 2016 (Slovenia–Croatia)RCTIBS7618-65(1.8×107 CFU/g) and
(2.5×107 CFU/g)
Lactobacillus acidophilus La-5 (1.8×107 CFU/g) and Bifidobacterium animalis ssp. lactis BB-12 (2.5×107 CFU/g)
Streptococcus thermophilus
4 weeksIBS–QoLWithout effect
Dapoigny et al., 2012 (France)Randomized double-blind pilot studyIBS47Int: 46.1±11.3
Plac: 48.0±10.8
6×108 CFULactobacillus casei variety rhamnosus LCR354 weeksGIQLIWithout effect
Riezzo et al., 2019 (Italy)RCTFC5619-65
42.4±13.8
15 days: four tablets daily
Then: two tablets daily
One tablet=1×108 CFU
Lactobacillus reuteri (LR) DSM 17938105 daysPAC–QoLWithout effect
Dimidi et al., 2019 (UK)RCTConstipation7518-65
Int: 35 (12)
Plac: 31 (10)
1.5×1010 CFU/dayBifidobacterium lactis NCC28184 weeksPAC–QoLWithout effect
Ibarra et al., 2018 (France)RCTAdults with functional constipation22418-701×109 or 1×1010 CFUBifidobacterium animalis subsp. lactis HN01928 daysPAC-QoLWithout effect
Ding et al., 2016 (China)RCT (prospective)Slow transit constipation93Plac: 48.3±11.3
Int: 47.2±10.7
0.63 gBifid triple viable capsules (BIFICO) and 8 g of soluble dietary fiber12 weeksGIQLIPositive effect
Gomi et al., 2018 (Japan)RCTPatients with functional GI disorders7920-64
Int: 41.1±10.1
Plac: 41.6±9.9
YIT 10347=3×107 CFU/mL
Streptococcus thermophilus YIT 2021=1×107
Bifidobacterium bifidum YIT 10347
Streptococcus thermophilus YIT 2021 (in both Plac and Int groups)
4 weeksSF-36 v2Without effect
Theodoropoulos et al., 2016 (Netherlands)RCTColectomy for cancer67Int: 66.8±2.17
Plac: 69±1.37
Sachets
12 g
Pediococcus pentosaceus 5-33:3, Leuconostoc mesenteroides 32-77:1, Lactobacillus paracasei ssp. paracasei 19, and L. plantarum 2362 and 2.5 g of each of the four fermentable fibers (prebiotics): b-glucan, inulin, pectin, and resistant starch15 daysGIQLI and EORTC QLQ-C30Without effect
Macnaughtan et al., 2020 (UK)RCTCirrhosis92 (68)18-786.5×109 CFULactobacillus casei Shirota (LcS)3 times per day for 6 monthsSF-36Without effect
Ahmadipour et al., 2020 (Iran)RCTInfant colic7221-90 days old
Int: 52.20±41.885 days
Plac: 49.36±23.321 days
5 drops of Pedilact
109 CFU
Lactobacillus rhamnosus, L. reuteri, Bifidobacterium infantis probiotics and fructooligosaccharide28 daysNot reportedWithout effect

RCT, randomized control trial; IBS, irritable bowel syndrome; FC, functional constipation; Int, intervention; Plac, placebo; CFU, colony forming unit; IBS-QoL, irritable bowel syndrome QoL; GIQLI, Gastrointestinal Quality of Life Index; PAC-QoL, Patient Assessment of Constipation QoL; SF-36, 36-item short form survey; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30..



Table 7 . Assessment of risk of bias for randomized and cross-over clinical trials using the Cochrane Risk of Bias 2 tool.

ReferenceRisk domain
Bias arising from the randomization processBias because of deviations from the intended interventionMissing outcome dataBias in outcome measurementBias in the selection of reported resultsOverall risk of bias
Fujimori et al., 2009LowHighHighLowSome concernsHigh
Chen et al., 2016Some concernsLowHighLowSome concernsHigh
Ahmadipour et al., 2020Some concernsLowLowLowLowSome concerns
Macnaughtan et al., 2020LowLowLowLowLowLow
Lee et al., 2014LowLowHighLowLowHigh
Theodoropoulos et al., 2016LowLowLowLowLowLow
Golkhalkhali et al., 2018LowLowLowLowLowLow
Radvar et al., 2020LowLowLowLowLowLow
Ringel-Kulka et al., 2011LowLowLowLowLowLow
Gomi et al., 2018LowLowLowLowLowLow
Ding et al., 2016LowLowSome concernsLowLowSome concerns
Cudmore et al., 2017LowLowLowLowLowLow
Ibarra et al., 2018LowLowHighLowLowHigh
Dimidi et al., 2019LowLowLowLowLowLow
Kommers et al., 2019LowLowHighLowLowHigh
Riezzo et al., 2019Some concernsSome concernsSome concernsLowLowSome concerns
Olgac et al., 2020Some concernsHighSome concernsLowSome concernsHigh
Choi et al., 2011LowLowHighLowLowHigh
Dapoigny et al., 2012LowLowSome concernsLowSome concernsSome concerns
Cappello et al., 2013LowLowSome concernsLowSome concernsSome concerns
Lorenzo-Zúñiga et al., 2014LowLowSome concernsLowSome concernsSome concerns
Abbas et al., 2014LowLowSome concernsLowSome concernsSome concerns
Choi et al., 2015LowLowLowLowLowLow
Šmid et al., 2016LowLowLowLowLowLow
Nobutani et al., 2017Some concernsSome concernsLowLowSome concernsSome concerns
Pinto-Sanchez et al., 2017LowLowLowLowLowLow
Giannetti et al., 2017LowLowLowLowLowLow
Preston et al., 2018Some concernsLowLowLowLowSome concerns
Aroniadis et al., 2019LowLowHighLowLowHigh
Francavilla et al., 2019LowLowLowLowLowLow
Catinean et al., 2019Some concernsSome concernsLowLowSome concernsSome concerns
El-Salhy et al., 2020LowLowLowLowLowLow


Table 8 . Assessment of risk of bias for non-randomized clinical trials using the Cochrane Risk of Bias 2 tool.

ReferenceRisk domain
Bias because of confoundingBias because of the selection of participantsBias in the classification of interventionBias because of deviations from the intended interventionBias because of missing outcome dataBias in outcome measurementBias in the selection of reported resultsOverall risk of bias
Drisko et al., 2006HighLowSome concernsLowSome concernsLowLowHigh
Xinias et al., 2018HighLowLowLowLowLowLowHigh
Ohigashi et al., 2011HighLowSome concernsLowSome concernsLowSome concernsHigh
Di Pierro et al., 2020HighLowLowLowLowLowLowHigh


Characteristics of included studies

The median age of participants across studies was 18-81 years, and the duration of probiotic supplementation ranged from 15 days to 16 weeks. In 36 studies, 2,942 patients with GI disease were supplemented with probiotics, and the QoL of individuals was assessed using a questionnaire. All studies were randomized trials that were published from 2006 to 2020. Five studies were conducted in Italy (Cappello et al., 2013; Giannetti et al., 2017; Francavilla et al., 2019; Riezzo et al., 2019; Di Pierro et al., 2020). Four studies were conducted in Japan (Fujimori et al., 2009; Ohigashi et al., 2011; Nobutani et al., 2017; Gomi et al., 2018). Four studies were conducted in the USA (Drisko et al., 2006; Ringel-Kulka et al., 2011; Preston et al., 2018; Aroniadis et al., 2019). Three studies were conducted in Korea (Choi et al., 2011; Lee et al., 2014; Choi et al., 2015). Two studies were conducted in France (Dapoigny et al., 2012; Ibarra et al., 2018). Two studies were conducted in the UK (Dimidi et al., 2019; Macnaughtan et al., 2020). Two studies were conducted in Iran (Ahmadipour et al., 2020; Radvar et al., 2020). One study was conducted in Norway (El-Salhy et al., 2020). One study was conducted in Canada (Pinto-Sanchez et al., 2017). One study was conducted in Romania (Catinean et al., 2019). One study was conducted in Pakistan (Abbas et al., 2014). One study was conducted in Spain (Lorenzo-Zúñiga et al., 2014). One study was conducted in Turkey (Olgac et al., 2020). One study was conducted in Brazil (Kommers et al., 2019). One study was conducted in Greece (Xinias et al., 2018). One study was conducted in Ireland (Cudmore et al., 2017). One study was conducted in China (Ding et al., 2016). One study was conducted in the Netherlands (Theodoropoulos et al., 2016). One study was conducted in Malaysia (Golkhalkhali et al., 2018). One study was conducted in Taiwan (Chen et al., 2016). One study was conducted in Slovenia-Croatia (Šmid et al., 2016).

Health-related quality of life (HRQOL) instruments

The HRQOL instruments used in the included studies were either generic or GI-specific measures. Five studies used SF-36. Thirteen studies used the IBS-QoL questionnaire (Drisko et al., 2006; Choi et al., 2011; Ringel-Kulka et al., 2011; Abbas et al., 2014; Lorenzo-Zúñiga et al., 2014; Choi et al., 2015; Šmid et al., 2016; Nobutani et al., 2017; Preston et al., 2018; Aroniadis et al., 2019; Catinean et al., 2019; Francavilla et al., 2019; El-Salhy et al., 2020). Three studies used the Gastrointestinal Quality of Life Index (GIQLI) (Chen et al., 2016; Ding et al., 2016; Theodoropoulos et al., 2016). Four studies used the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) (Ohigashi et al., 2011; Theodoropoulos et al., 2016; Golkhalkhali et al., 2018; Radvar et al., 2020). One study used the Functional Disability Inventory (FDI) (Giannetti et al., 2017). One study used the Pittsburgh Sleep Quality Index-Japanese version (PSQI-J) (Nobutani et al., 2017). One study used the Functional Assessment of Cancer Therapy (FACT) (Lee et al., 2014). One study used the modified Gastrointestinal QoL (mGIQL). One study used the Inflammatory Bowel Disease Questionnaire (IBDQ) (Fujimori et al., 2009). One study used the KINDL Health-Related Quality of Life (KINDL HRQOL) (Olgac et al., 2020). One study used the “Document of scientific support to the protocol for the diagnosis and follow-up of celiac disease” (Di Pierro et al., 2020). Two studies did not report the method used to measure the QoL (Xinias et al., 2018; Ahmadipour et al., 2020).

Probiotics

Among the 36 studies, eight different bacterial genera were used as probiotic supplements: a) Lactobacillus, b) Bifidobacterium, c) Streptococcus, d) Saccharomyces, e) Bacillus, f) Enterococcus, g) Pediococcus, and h) Clostridium. L. gasseri species were used as a supplement in two studies (Cappello et al., 2013; Nobutani et al., 2017). L. acidophilus was used in nine studies. L. plantarum was used in five studies (Drisko et al., 2006; Cappello et al., 2013; Lorenzo-Zúñiga et al., 2014; Theodoropoulos et al., 2016; Cudmore et al., 2017). B. bifidum was used in five studies (Drisko et al., 2006; Cudmore et al., 2017; Golkhalkhali et al., 2018; Gomi et al., 2018; Kommers et al., 2019). L. casei was used in seven studies (Drisko et al., 2006; Dapoigny et al., 2012; Cappello et al., 2013; Golkhalkhali et al., 2018; Kommers et al., 2019; Macnaughtan et al., 2020; Radvar et al., 2020). L. salivarius and L. sporogenes were used in one study (Cappello et al., 2013). L. brevis (Drisko et al., 2006), L. paracasei (Theodoropoulos et al., 2016), Leuconostoc mesenteroides (Theodoropoulos et al., 2016), B. breve (Radvar et al., 2020), Bacillus subtilis (Choi et al., 2015), B. natto (Choi et al., 2015), E. faecalis (Ohigashi et al., 2011), P. pentosaceus (Ohigashi et al., 2011), and C. butyricum (Chen et al., 2016) were each used in one study. Meanwhile, Lactobacillus bulgaricus (Drisko et al., 2006; Cudmore et al., 2017; Radvar et al., 2020), Bifidobacterium animalis (Cappello et al., 2013; Šmid et al., 2016; Ibarra et al., 2018), and L. reuteri (Riezzo et al., 2019; Ahmadipour et al., 2020; Olgac et al., 2020) were each used in three studies. L. rhamnosus was used in five studies (Drisko et al., 2006; Lee et al., 2014; Cudmore et al., 2017; Ahmadipour et al., 2020; Radvar et al., 2020). Lactococcus lactis (Golkhalkhali et al., 2018; Kommers et al., 2019), Saccharomyces boulardii (Choi et al., 2011; Abbas et al., 2014), and P. acidilactici (Drisko et al., 2006; Ibarra et al., 2018) were each used in two studies. B. longum was used in eight studies (Drisko et al., 2006; Fujimori et al., 2009; Cappello et al., 2013; Chen et al., 2016; Golkhalkhali et al., 2018; Ahmadipour et al., 2020; Di Pierro et al., 2020; Radvar et al., 2020). B. lactis (Ringel-Kulka et al., 2011; Xinias et al., 2018; Dimidi et al., 2019; Kommers et al., 2019) and Streptococcus thermophilus (Drisko et al., 2006; Šmid et al., 2016; Gomi et al., 2018; Radvar et al., 2020) were each used in four studies. Most probiotic species that were used as supplements in the RCT studies included Lactobacillus acidophilus, B. longum, and L. casei. Lactobacillus and Bifidobacterium are the two most commonly studied probiotic genera in clinical GI studies. The details of this section are summarized in Table 9.

Table 9 . Genus and species of probiotic supplementation in the included studies.

GenusSpeciesStudies wherein probiotic supplements were effectiveStudies wherein probiotic supplements were ineffective
LactobacillusLactobacillus gasseriCappello et al., 2013Nobutani et al., 2017
Lactobacillus acidophilus1)Cappello et al., 2013, Kommers et al., 2019, Cudmore et al., 2017, Ringel-Kulka et al., 2011, Radvar et al., 2020, Golkhalkhali et al., 2018, Lee et al., 2014, Ohigashi et al., 2011Šmid et al., 2016
Lactobacillus plantarumLorenzo-Zúñiga et al., 2014, Cappello et al., 2013, Drisko et al., 2006, Cudmore et al., 2017, Theodoropoulos et al., 2016-
Lactobacillus casei1)Cappello et al., 2013, Drisko et al., 2006, Kommers et al., 2019, Radvar et al., 2020, Golkhalkhali et al., 2018Dapoigny et al., 2012, Macnaughtan et al., 2020
Lactobacillus salivariusCappello et al., 2013-
Lactobacillus sporogenesCappello et al., 2013-
Lactobacillus brevisDrisko et al., 2006-
Lactobacillus bulgaricusDrisko et al., 2006, Cudmore et al., 2017, Radvar et al., 2020-
Lactobacillus salivariusDrisko et al., 2006-
Lactobacillus rhamnosusDrisko et al., 2006, Cudmore et al., 2017, Radvar et al., 2020, Lee et al., 2014Ahmadipour et al., 2020
Lactobacillus reuteriOlgac et al., 2020Riezzo et al., 2019, Ahmadipour et al., 2020
Lactococcus lactisKommers et al., 2019, Golkhalkhali et al., 2018-
Lactobacillus paracaseiTheodoropoulos et al., 2016-
Leuconostoc mesenteroidesTheodoropoulos et al., 2016-
BifidobacteriumBifidobacterium bifidumDrisko et al., 2006, Kommers et al., 2019, Cudmore et al., 2017, Abbas et al., 2014Gomi et al., 2018
Bifidobacterium longum1)Cappello et al., 2013, Drisko et al., 2006, Radvar et al., 2020, Golkhalkhali et al., 2018, Di Pierro et al., 2020, Chen et al., 2016, Fujimori et al., 2009Ahmadipour et al., 2020
Bifidobacterium animalisCappello et al., 2013Šmid et al., 2016, Ibarra et al., 2018
Bifidobacterium lactisKommers et al., 2019, Xinias et al., 2018, Ringel-Kulka et al., 2011Dimidi et al., 2019
Bifidobacterium breveRadvar et al., 2020-
StreptococcusStreptococcus thermophilusDrisko et al., 2006, Radvar et al., 2020Šmid et al., 2016, Gomi et al., 2018
SaccharomycesSaccharomyces boulardiiAbbas et al., 2014, Choi et al., 2011-
BacillusBacillus subtilisChoi et al., 2015-
Bacillus nattoOhigashi et al., 2011-
EnterococcusEnterococcus faecalisChoi et al., 2015-
PediococcusPediococcus pentosaceusTheodoropoulos et al., 2016-
Pediococcus acidilacticiDrisko et al., 2006Ibarra et al., 2018
ClostridiumClostridium butyricumChen et al., 2016-

1)Lactobacillus and Bifidobacterium were the most common genera of probiotics that were used to study the effects of probiotic supplementation in clinical gastrointestinal investigations..

-, not available..



Overall, the investigation of the effect of different types of probiotic supplementation on the QoL of GI patients in RCT studies showed that 23 studies reported improvement in the QoL of patients (Drisko et al., 2006; Fujimori et al., 2009; Choi et al., 2011; Ringel-Kulka et al., 2011; Ohigashi et al., 2011; Cappello et al., 2013; Abbas et al., 2014; Lee et al., 2014; Lorenzo-Zúñiga et al., 2014; Choi et al., 2015; Chen et al., 2016; Cudmore et al., 2017; Giannetti et al., 2017; Nobutani et al., 2017; Pinto-Sanchez et al., 2017; Golkhalkhali et al., 2018; Preston et al., 2018; Ringel-Kulka et al., 2011; Xinias et al., 2018; Kommers et al., 2019; Di Pierro et al., 2020; El-Salhy et al., 2020; Olgac et al., 2020; Radvar et al., 2020), whereas 12 studies reported no improvement in the QoL of patients after probiotic supplementation (Dapoigny et al., 2012; Ding et al., 2016; Šmid et al., 2016; Theodoropoulos et al., 2016; Gomi et al., 2018; Ibarra et al., 2018; Aroniadis et al., 2019; Dimidi et al., 2019; Riezzo et al., 2019; Ahmadipour et al., 2020; Francavilla et al., 2019; Macnaughtan et al., 2020) (Table 6).

Irritable bowel syndrome (IBS)

Based on evidence provided by the included studies, supplementation with the following probiotic species has been reported to be effective in IBS: Bifidobacterium longum W11 and Bacillus spp. (Catinean et al., 2019); bifidobacteria (Giannetti et al., 2017); Bifidobacterium longum (Pinto-Sanchez et al., 2017); Bacillus subtilis and Streptococcus faecium (Pinto-Sanchez et al., 2017); Saccharomyces boulardii (Abbas et al., 2014); Lactobacillus plantarum, L. casei subp. rhamnosus, L. gasseri, Bifidobacterium infantis, L. acidophilus, L. salivarius, L. sporogenes, and Streptococcus thermophilus (Cappello et al., 2013); L. plantarum and Pediococcus acidilactici (Lorenzo-Zúñiga et al., 2014); Saccharomyces boulardii (Choi et al., 2011); L. acidophilus, B. bifidum, L. rhamnosus, L. plantarum, B. infantis, L. salivarius, L. bulgaricus, L. casei, L. brevis, and Streptococcus thermophilus (Drisko et al., 2006). Despite these results, no differences were observed with regard to the effects of supplementation with probiotics or placebos among patients with IBS when using the following probiotic species: L. casei, L. plantarum, B. animalis subsp. lactis Bi1 LMG P-17502, B. breve Bbr8 LMG P-17501, and B. breve Bl10 LMG P-17500 (Francavilla et al., 2019); L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 (Francavilla et al., 2019); L. acidophilus, B. animalis ssp, and S. thermophilus (Šmid et al., 2016); and L. casei and L. casei rhamnosus LCR35 (Dapoigny et al., 2012).

Rectal cancer

Based on evidence provided by the included studies, the following probiotic species have been demonstrated to improve overall health status and QoL and minimize certain side effects of chemotherapy in patients with cancer: Lactobacillus casei PXN 37, L. rhamnosus PXN 54, Streptococcus thermophilus PXN 66, Bifidobacterium breve PXN 25, L. acidophilus PXN 35, B. longum PXN 30, and L. bulgaricus PXN 39 (Radvar et al., 2020); L. acidophilus BCMCR 12130, L. casei BCMCR 12313, L. lactis BCMCR 12451, B. bifidum BCMCR 02290, B. longum BCMCR 02120, and B. infantis BCMCR 02129 (Golkhalkhali et al., 2018); and Bacillus natto and L. acidophilus (Ohigashi et al., 2011). However, no significant changes in cancer-related QoL were observed in patients with cancer receiving supplementation with probiotics or placebo when using the following probiotic species: Pediococcus pentosaceus 5-33:3, Leuconostoc mesenteroides 32-77:1, L. paracasei ssp. paracasei 19, and L. plantarum 2362 (Theodoropoulos et al., 2016) and Lacidofil (L. rhamnosus R0011, L. acidophilus R0052) (Lee et al., 2014).

Functional gastrointestinal disorders (FGIDs)

According to several studies, probiotic supplementation with the following species had no effect on the QoL of patients with FGIDs: Bifidobacterium bifidum YIT 10347 and Streptococcus thermophilus YIT 2021 (in both placebo and intervention groups) (Gomi et al., 2018) and L. acidophilus NCFM (L-NCFM) and B. lactis Bi-07 (B-LBi07) (Ringel-Kulka et al., 2011).

Functional constipation (FC)

Based on evidence provided by the included studies, supplementation with the following probiotic species could improve FC and the QoL of patients: Lactobacillus reuteri DSM 17938 or lactulose (Olgac et al., 2020), Bifidobacterium lactis (BL04), B. bifidum (Bb-06), L. acidophilus (La-14), L. casei (Lc-11), and Lactococcus lactis (LL-23) (Kommers et al., 2019); B. lactis NCC2818 (Dimidi et al., 2019); B. lactis BB12 (Xinias et al., 2018); and Lactobacillus rhamnosus PXN 54 (NCIMB 30188), B. bifidum PXN 23 (NCIMB 30179), L. acidophilus PXN 35 (NCIMB 30184), L. plantarum PXN 47 (NCIMB 30187), and L. bulgaricus PXN 39 (NCIMB 30186) (Cudmore et al., 2017). However, B. animalis subsp. lactis HN019 (Ibarra et al., 2018), L. reuteri DSM 17938 (Riezzo et al., 2019), and Bifid triple viable capsules (Ding et al., 2016) could not improve the QoL of these patients. The various methods used to assess gut microbiota and other key clinical findings for GI diseases are shown in Table 10.

Table 10 . Notable outcomes of selected RCT studies assessing the effects of probiotics on GI diseases.

ReferenceGut microbiota assessmentOutcomes of GI symptoms
Macnaughtan et al., 2020, UK--
Giannetti et al., 2017, Italy-In IBS, Bifidobacteria supplementation resulted in a complete resolution of abdominal pain in a significantly higher proportion of children
Cappello et al., 2013
Italy (Rome)
--
Cudmore et al., 2017, Ireland-Symptoms of constipation improved
Fujimori et al., 2009, Japan-Emotional function increased in the probiotic and synbiotic groups
Gomi et al., 2018, Japan-The YIT10347 group had significantly higher relief rates of overall gastrointestinal symptoms, upper gastrointestinal symptoms, flatus, and diarrhea than the placebo group
Francavilla et al., 2019, Italy·Using plate counts and 16S rRNA gene-based analysis
·Fecal samples (5 g) were mixed with 45 mL of sterilized physiological solution and homogenized. Viable bacterial cells were counted as described by De Angelis et al.
·To determine the identities of bacteria, sequences were first queried using a distributed BLASTn.NET algorithm24 against 16S bacterial sequences derived from NCBI.
-
Radvar et al., 2020, Iran-Body weight decreased in the synbiotic and placebo groups
Aroniadis et al., 2019, USA16S rRNA sequencing-
Chen et al., 2016, Taiwan-Complaints of abdominal pain, abdominal bloating, excessive passage of gas, foul smell of flatulence, belching, abdominal noises, and heartburn were significantly improved in the entire sample
Dapoigny et al., 2012, FranceExtraction of total bacterial DNA (QIAamp Fast DNA Stool Mini Kit, QIAGEN), the presence of Lactobacillus casei variety rhamnosus was specifically determined by qualitative polymerase chain reaction (PCR - primer pairs hyb-21) – cycles of amplification.A decrease in the abdominal pain severity score was observed with LCR35
Choi et al., 2015, Korea-The abdominal pain/discomfort score in treatment group 4 was more prominently improved compared with that of the placebo group
In patients with constipation-predominant IBS, the improvements in stool frequency and consistency were significantly higher in treatment groups 4 and 1, respectively, than those in the placebo group
There were more favorable tendencies of effects on bloating in all treatment groups than in the placebo group
El-Salhy et al., 2020, Norway16S rRNA gene sequencing-
Ding et al., 2016, China-During the intervention period, patients who were treated with the synbiotic exhibited increased stool frequency, improved stool consistency, decreased colonic transit time, and improved constipation-related symptoms
Ohigashi et al., 2011, Japan-Defecation frequency, anal pain, and Wexner score were significantly poorer in the rectal group than in the colonic group
Ringel-Kulka et al., 2011, USAQuantitative real-time polymerase chain reaction of fecal samplesAbdominal bloating improved in the probiotic group compared with the placebo group at 4 and 8 weeks
Dimidi et al., 2019, UKQuantitative polymerase chain reaction-
Šmid et al., 2016, Slovenia & Croatia-Significant improvements in bloating severity, satisfaction with bowel movements
Golkhalkhali et al., 2018, Malaysia-Nausea, vomiting, and diarrhea significantly improved in the treatment group
Theodoropoulos et al., 2016, Netherlands-Differences in the EORTC QLQ-C30 “diarrhea” domain score from baseline were better after synbiotic administration after 3 (P=0.04) and 6 months (P=0.003)
Nobutani et al., 2017, Japan·Purified DNA was used as a template for the following two-step polymerase chain reaction.
·Fecal microbiota was measured using fecal bacterial 16S rDNA V4-V6 region-targeted pyrosequencing.
CP2305 favorably changed the fecal characteristics compared with placebo among patients with IBS with either diarrhea or constipation subtypes
Drisko et al., 2006, USA-Significant improvements in pain were observed (P=0.05)

RCT, randomized controlled trial; GI, gastrointestinal; IBS, irritable bowel syndrome; NCBI, National Center for Biotechnology Information; QoL, quality of life; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30; -, not available..


DISCUSSION

To the best of our knowledge, this study is the first systematic evaluation examining how different probiotic species affect the QoL of patients with GI disorders. According to the 10 different QoL assessment systems used in recent clinical studies (SF-36, IBS-QoL, GIQLI, EORTC QLQ-C30, FDI, PSQI-J, FACT, mGIQL, IBDQ, and KINDL HRQOL), different probiotic species (especially Lactobacillus acidophilus, Bifidobacterium longum, and L. casei) significantly improved the QoL of GI patients. Moreover, the clinical trial studies included in this systematic review did not report any side effects of probiotic supplementation. Generally, based on the studies reviewed in this article, different bacterial strains effectively improved the QoL of patients with IBS, rectal cancer, and FC; however, they did not improve the QoL of FC and related diseases. There is a direct relationship between QoL and psychological and physical parameters. Moreover, psychological pathways are responsible for every benefit of probiotics. The combined delivery of Bifidobacterium and Lactobacillus species in humans reduces responses to stress and negative stimuli, suggesting that probiotics indirectly affect QoL through perception and mood (Messaoudi et al., 2011; Steenbergen et al., 2015; McKean et al., 2017).

Probiotic supplementation and IBS

After the idea linking the gut microbiome with human illnesses was put forward, researchers have investigated whether microbiome changes could be found in GI diseases (Pimentel and Lembo, 2020). Several studies have identified less microbial diversity or richness in individuals with IBS than in those without (Codling et al., 2010; Carroll et al., 2012; Jeffery et al., 2012; Ng et al., 2013; Giamarellos-Bourboulis et al., 2015; Maharshak et al., 2018). However, one study did not (Ponnusamy et al., 2011). The majority of trials have assessed how well probiotics work in patients with IBS, many of whom have significant cognitive impairments (Quigley, 2009). The results from a meta-analysis of 15 controlled studies discovered that probiotics decreased pain levels and symptom severity in IBS (Didari et al., 2015). However, the best strain, dose, formulation, and length of treatment remain unknown (Pimentel and Lembo, 2020).

When probiotics were utilized for treating IBS, Bifidobacterium infantis 35624 demonstrated a notable enhancement in alleviating abdominal discomfort/pain, bloating/distention, and/or bowel movement difficulties compared with placebo (O’Mahony et al., 2005). Moreover, fecal consistency was significantly improved by probiotic supplementation compared with placebo, which could indirectly improve patients’ QoL (Cha et al., 2012). Hollister et al., examined how bacterial families are linked to daily GI symptoms and additional forms of pain including heartburn, joint pain, muscle aches, back pain, and headache. They found that various families under Firmicutes (Dehalobacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae) are associated with lower extra-intestinal pain (Hollister et al., 2020). Moreover, in vitro and in vivo studies demonstrated that probiotics can effectively decrease bloating and abdominal symptoms in patients with IBS (Kim et al., 2003; Aragon et al., 2010; Wong et al., 2015; Staudacher et al., 2017).

Probiotic supplementation and cancer

Cancer and its treatments are commonly accompanied by fatigue. Several studies have demonstrated intestinal microbiome changes in patients with cancer, chronic fatigue syndrome, and other neuropsychiatric disorders (Hajjar et al., 2021). Hajjar et al., revealed that cancer patients with varying levels of fatigue may exhibit diverse gut microbiome compositions. Because of the significance of the microbiome in mucosal immunity and the growing understanding of the link between the gut-brain axis and fatigue and other symptoms, disruption in intestinal microbiota may play a key role in these conditions. On the other hand, improving the microbiome can reduce fatigue severity in patients with cancer and improve their QoL. This research indicates the necessity for further studies on how adjusting the gut microbiome can affect fatigue and enhance QoL in individuals with cancer (Hajjar et al., 2021).

To date, the exact mechanisms behind the effect of gut microbiota on cancer remain unknown. Nevertheless, the gut microbiome could have a significant impact on cancer development through various mechanisms (Grivennikov et al., 2012). First, there are differences in the gut microbial content between individuals with cancer and those without, which may have carcinogenesis effects and contribute to cancer development. For instance, research on the human microbiome revealed notable variations in the prevalence of certain microbes in the cancer group compared with the control group (Bultman, 2014). The second mechanism is the well-known link between inflammation and intestinal microbiota and metabolism, which are cancer characteristics (Tlaskalova-Hogenova et al., 2014). In the metabolic pathway, plant-derived foods are metabolized by intestinal microbiota to biologically active compounds that may be carcinogenic (Tlaskalova-Hogenova et al., 2014). Some studies suggested that the perioperative administration of probiotics/synbiotics reduces the prevalence of side effects and improves the QoL and survival of patients with colorectal cancer (Amitay et al., 2020).

Probiotic supplementation and FC

The prevalence of FC is high in the elderly and is associated with poor QoL. According to previous studies, the most common symptoms of FC that significantly affect the health-related QoL of adults include stool stiffness, squeezing, and feeling of anal obstruction (Norton, 2006; Arco et al., 2022), wherein patients with FC scored lower in all dimensions of the EQ5D3L than those without. European Quality of Life 5 Dimensions 3 Level Version (EQ5D3L) is recognized as an effective and useful assessment tool for comparing QoL in different conditions. However, some researchers also recommend the use of FC-specific QoL measurements, such as assessing a patient’s QoL in constipation (Marquis et al., 2005). Moreover, FC has been reported to be associated with serious mental illness (Merkel et al., 1993; Towers et al., 1994). One study showed that patients with FC are more likely to experience depression and anxiety, according to the corresponding EQ5D3L subscale. Thus, primary care teams and specialists should take into account the impact of FC on the QoL of the elderly, considering the wide range of factors to enhance the overall health of this group (Arco et al., 2022). Additionally, evidence indicated that probiotic therapy has a positive impact on defecation frequency, stool consistency, and constipation condition in adults and children (Chmielewska and Szajewska, 2010).

Mechanism of action of probiotics in improving the QoL of GI patients

Age, health conditions, and food choices play a significant role in shaping the microbiota composition. A previous study showed that the microorganisms found in individuals between the ages of 65 and 96 years are distinct from those in younger adults, showing elevated levels of cluster IV of Bacteroides and Clostridium, as well as specific sequences unique to older individuals (Claesson et al., 2011). Various illnesses are linked to alterations in microflora (known as dysbiosis), ranging from GI conditions such as IBS and inflammatory bowel disease to non-GI conditions such as obesity and diabetes (Shanahan, 2013). In dysbiosis, the diversity of commensal microbiota is decreased, and the interaction between the immune system and the gut microbiota is disturbed. In fact, some gut bacteria increase the production of proinflammatory factors, whereas others cause the production of proinflammatory factors (de Oliveira et al., 2017). Probiotic consumption ensures the effect of healthy microbiota homeostasis in the intestinal mucosa by modulating systemic immune responses and seems to be effective as supportive treatment in GI disorders. The mechanism of action of probiotics in improving dysbiosis includes the following: improving mucus secretion, producing antimicrobial peptides, maintaining the function of the gastric-intestinal-epithelial barrier, and ensuring proper interaction between intestinal microbiota and mucosal immune cells (Bron et al., 2017; López-Moreno et al., 2020). Moreover, probiotics can reverse dysbiosis by preventing the colonization of pathogenic bacteria in the gut and maintaining the intestinal mucosa through the production of short-chain fatty acids (Dazıroğlu and Yıldıran, 2023).

With regard to nutrition, the impact of eating on the microbiome has been thoroughly researched. A habitual long-term diet is strongly associated with enterotypes. Animal fat/protein is linked to enterotype 1, whereas carbohydrates are linked to enterotype 2. On the other hand, acute feeding with diets containing different fats and non-starch polysaccharides alters the human microbial phase, indicating that the manipulation of major dietary nutrients is responsible for most changes in microbiota (Faith et al., 2011; Wu et al., 2011). Some approaches for regulating GI flora, especially the use of probiotic organisms, have been sought as ways to promote health and, in some cases, treatment of diseases (Whelan and Quigley, 2013).

In addition, the gut microbiota is associated with many GI-related syndromes, including IBS. Hence, there is an increasing focus on controlling the microbiota as a treatment alternative. Since microbial flora is connected to the CNS via the cerebrointestinal axis, additional changes in this relationship have been identified as the mechanisms of IBS, which function in the intestines through central and peripheral pathways and microbial metabolites (Distrutti et al., 2004; Parkes et al., 2008; Bhattarai et al., 2017).

Limitations and future directions

This review has some limitations. First, there may be language bias as our search only used English sources. Second, the evidence level of the systematic review is restricted by included studies’ evidence level. Third, we did not exclude studies that used unreliable HRQOL tools. Finally, systematic studies on probiotic formulations did not find enough evidence to explain how each species in the combination works. In future studies, the effects of supplementation with different types of probiotics in combination and alone need to be studied to determine the exact mechanisms of each probiotic species.

This systematic review provides a new overview of how probiotic supplementation affects QoL in patients with GI diseases and outlines potential areas for future research. Based on our review of available clinical trial studies, we found that patients with GI diseases reported significant improvement in HRQOL after probiotic supplementation. However, more in vitro and in vivo studies and clinical trials on probiotics are needed to investigate the precise ways in which probiotics affect GI diseases.

ACKNOWLEDGEMENTS

We hereby acknowledge the student research committee of Kermanshah University of Medical Sciences for the financial support of this project.

FUNDING

This study was supported by Kermanshah University of Medical Science (No. 4020345).

AUTHOR DISCLOSURE STATEMENT

The authors declare no conflict of interest.

AUTHOR CONTRIBUTIONS

Concept and design: JM, AS. Analysis and interpretation: MAZ. Data collection: MAZ. Validation: YA, SM, SH. Writing the article: YA, JM, SM, SH. Critical revision of the article: YP, SM, FM. Statistical analysis: FM, YA. Obtained funding: FM, YA, SH, MAZ. Final approval of the article: all authors. Overall responsibility: AS.

Fig 1.

Figure 1.Flow chart of the study selection process.
Preventive Nutrition and Food Science 2024; 29: 237-255https://doi.org/10.3746/pnf.2024.29.3.237

Table 1 . IBS-related disease: characteristics of selected clinical trials included in the review

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
El-Salhy et al., 2020 (Norway)RCTIBS16539.9±9.030 g FMT or 60 g FMT at a ratio of 1:1:1 The material for FMTFMT3 monthsIBS-QoLPositive effect
Catinean et al., 2019 (Romania)RCTIBS9018-75
G1=38.77±10.96
G2=39.07±16.00
G3=40.37±11.95
G2=7 days: 1 cap
27 days: 2 cap
G1=Bifidobacterium longum W11
G2=five Bacillus spp.
34 days
G1 and G3=10+24
G2=34
IBS-QoL (SF-36)Positive effect
Preston et al., 2018 (USA)RCTIBS86Plac: 39.9
Int: 40.6
2 capsules
50×109 CFU
Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR212 weeksIBS-QoLPositive effect
Giannetti et al., 2017 (Italy)RCTChildren with IBS and functional dyspepsia738.0-17.93 billion (3×109) of Bifidobacterium longum BB536, 1 billion (1×109) of B. infantis M-63, 1 billion (1×109) of B. breve M-16V3 Bifidobacteria:M-63breve M-16Vlongum BB53616 weeks:
2-week run-in phase
6 weeks Int
2-week “washout”
Afterward, each patient was switched to the other group
6 weeks Int
FDIPositive effect
Pinto-Sanchez et al., 2017 (Canada)RCTIBS44Int: 46.5 (30-58)
Plac: 40.0 (26-57)
1.0E+10Bifidobacterium longum NCC3001 (BL)6-week treatment
10 week follow-up
SF-36Positive effect
Nobutani et al., 2017 (Japan)RCTIBS30Int: 52.6±20.1
Plac: 45.9±19.5
13×108 CFULactobacillus gasseri CP23054 weeksIBS-QoL and PSQI-JPositive effect
Choi et al., 2015 (Korea)RCTNon-diarrheal-type IBS28520-73 (47)Group 1: 1.0×1010
CFU
Groups 2 and 3: 1.5×1010
Group 4: 3×1010
Bacillus subtilis and Streptococcus faecium4 weeksIBS-QoLPositive effect
Abbas et al., 2014 (Pakistan)RCTIBS-D72
64
(completed)
18-60
Int:
37.7±11.6
Plac:
33.0±12.0
750 mg/dSaccharomyces boulardii2-week run-in
6 weeks Int
IBS-QoLPositive effect
Lorenzo-Zúñiga et al., 2014 (Spain)RCTIBS7320-70
Int: 47.5±13.1
46.3±11.6
Plac: 46.5±13.1
1-3×1010 CFU or 3-6×109Two Lactobacillus plantarum (CECT7484 and CECT7485) and one Pediococcus acidilactici (CECT7483)6 weeksIBS-QoLPositive effect
Cappello et al., 2013 (Italy)RCTIBS6438.7±12.65×109 Lactobacillus plantarum, 2×109 L. casei subp. rhamnosus and 2×109 L. gasseri, 1×109 Bifidobacterium infantis and 1×109 B. longum, 1×109 L. acidophilus, 1×109 L. salivarius and 1×109 L. sporogenes and 5×109 Streptococcus thermophilus
Prebiotic inulin 2.2 g
Lyophilized bacteria: L. plantarumL. casei subp. rhamnosusL. gasseriBifidobacterium infantisL. acidophilusL. salivariusL. sporogenesStreptococcus thermophilus
Prebiotic inulin
6 weeks
(2-week run-in and 4-week treatment)
SF-36Positive effect
Choi et al., 2011 (Korea)RCTIBS6741±132×1011Saccharomyces boulardii4 weeksIBS-QoLPositive effect
Drisko et al., 2006 (USA)Open-label pilot study
Prospective outcome study
IBS2024-8110 billion CFULactobacillus acidophilus, Bifidobacterium bifidum, L. rhamnosus, L. plantarum, B. infantis, L. salivarius, L. bulgaricus, L. casei, L. brevis, and Streptococcus thermophilus1 yearIBS-QoLPositive effect

RCT, randomized control trial; IBS, irritable bowel syndrome; FMT, fecal microbiota transplantation; QoL, quality of life; IBS-QoL, irritable bowel syndrome QoL; IBS-D, diarrhea-dominant irritable bowel syndrome; SF-36, 36-item short form survey; CFU, colony forming unit; FDI, Functional Disability Inventory; Int, intervention; Plac, placebo; PSQI-J, Pittsburgh Sleep Quality Index.


Table 2 . Constipation-related disease: characteristics of selected clinical trials included in the review

ReferenceType of studyClinical setting/populationSample sizeAgeDaily doseProbiotic speciesDuration of interventionSystemMain outcomes
Olgac et al., 2020 (Turkey)RCTChildren with FC494-16 years1×108 CFULactobacillus reuteri DSM 17938 or lactulose4 weeksKINDL HRQOLPositive effect
Kommers et al., 2019 (Brazil)RCTFemale university students with intestinal constipation6320-40 years
Int: 27.15±5.52
Plac: 24.38±5.41
109 CFU of each oneBifidobacterium lactis (BL04), B. bifidum (Bb-06), Lactobacillus acidophilus (La-14), L. casei (Lc-11), Lactococcus lactis (LL-23)45 daysPAC-QoLPositive effect
Xinias et al., 2018 (Greece)Non-randomized clinical trialInfants with FC653-13 weeks
Int: 1.4±0.8
Plac: 1.7±0.9
Not reportedBifidobacterium lactis BB121 monthNot reported (parents completed a QoL)Positive effect
Cudmore et al., 2017 (Ireland)RCTChronic, FC6918-80 years6×108 CFU twice dailyLactobacillus rhamnosus PXN 54 (NCIMB 30188), Bifidobacterium bifidum PXN 23 (NCIMB 30179), L. acidophilus PXN 35 (NCIMB 30184), L. plantarum PXN 47 (NCIMB 30187), and L. bulgaricus PXN 39 (NCIMB 30186)
Also psyllium and inulin
4 weeksPAC-QoLPositive effect

RCT, randomized control trial; FC, functional constipation; CFU, colony forming unit; QoL, quality of life; KINDL HRQOL, KINDL Health-Related QoL; PAC-QoL, Patient Assessment of Constipation QoL.


Table 3 . Functional gastrointestinal disorders (FGIDs): characteristics of selected clinical trials included in the review

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of intervention (weeks)SystemMain outcomes
Ringel-Kulka et al., 2011 (USA)RCTFunctional bowel disorders6018-65 Mean age Int: 36 Plac: 37Twice a day (2×1011 CFU CFU/d)Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07)8IBS-QoLPositive effect

RCT, randomized control trial; CFU, colony forming unit; IBS-QoL, irritable bowel syndrome-quality of life; Int, intervention; Plac, placebo.


Table 4 . Colorectal cancer-related disease: characteristics of selected clinical trials included in the review

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Radvar et al., 2020 (Iran)RCTRectal cancer38Int: 57.58±12.78 Plac: 62.89±13.932 times a day 1×108 CFU/gLactobacillus casei PXN 37, L. rhamnosus PXN 54, Streptococcus thermophilus 81 PXN 66, Bifidobacterium breve PXN 25, L. acidophilus PXN 35, B. longum PXN 30, L. bulgaricus PXN 39, FOS (fructooligosaccharide), magnesium stearate (source: mineral and vegetable), and vegetable capsule (hydroxypropyl methyl cellulose)6 weeksEORTC QLQ-C30Positive effect
Golkhalkhali et al., 2018 (Malaysia)RCTColorectal cancer140<18Two sachets daily 30 billion (CFUs) per sachetLactobacillus acidophilus BCMCR 12130, L. casei BCMCR 12313, Lactobacillus lactis BCMCR 12451, Bifidobacterium bifidum BCMCR 02290, B. longum BCMCR 02120, and B. infantis BCMCR 021298 weeksEORTC QLQ-C30Positive effect
Lee et al., 2014 (Korea)RCTColorectal cancer6056.18±8.86Twice a day 2×109 CFULacidofil (Lactobacillus rhamnosus R0011 andL. acidophilus R0052)12 weeksFACTPositive effect
Ohigashi et al., 2011 (Japan)Questionnaire-based studyColorectal cancer6363±910 mg of Bacillus natto and 30 mg of Lactobacillus acidophilusB. natto and L. acidophilus3 monthsSF-36 and EORTC QLQ-C30Positive effect

RCT, randomized control trial; Int, intervention; Plac, placebo; CFU, colony forming unit; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30; FACT, Functional Assessment of Cancer Therapy; SF-36, 36-item short form survey.


Table 5 . Other diseases: characteristics of selected clinical trials included in the review

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Di Pierro et al., 2020 (Italy)Non-randomized clinical trialNon-celiac gluten sensitivity30Int: 46.87±17.06 Plac: 43.53±18.941 dose/day 1×109 CFU (1 billion)Bifidobacterium longum ES1 or GFD3 monthsDocument of scientific support to the protocol for the diagnosis and follow-up of celiac diseasePositive effect
Chen et al., 2016 (Taiwan)RCTGastric bypass surgery5318-60 35.1±8.3Twice daily A: 5×109 CFU (5 billion) B: 8×109 CFU (8 billion)A: 1 g Clostridium butyricum MIYAIRI B: 300 mg Bifidobacterium longum BB5362 weeksmGIQLPositive effect
Fujimori et al., 2009 (Japan)RCTUlcerative colitis83Pro=36±16 Pre=37±13 Syn=35±102×109 CFUBifidobacterium longum Also prebiotic (psyllium) and synbiotic4 weeksIBDQPositive effect

RCT, randomized control trial; Int, intervention; Plac, placebo; Pro, probiotics; Pre, prebiotics; Syn, symbiotic; CFU, colony forming unit; GFD, gluten-free diet; mGIQL, modified Gastrointestinal QoL Index; IBDQ, Inflammatory Bowel Disease Questionnaire.


Table 6 . Characteristics of included studies that did not find any effect

ReferenceType of studyClinical setting/populationSample sizeAge (year)Daily doseProbiotic speciesDuration of interventionSystemMain outcomes
Francavilla et al., 2019 (Italy)RCTPatients with celiac disease and IBS109Age 18 years and above
Int: 43.3 (18.8-62.2)
Plac: 44.6 (19.3-63.4)
5×109 CFU/sachet+5×109 CFU/sachet+10×109 CFU/sachet+10×109 CFU/sachet+10×109 CFU/sachetLactobacillus casei LMG 101/37 P-17504 (5×109 CFU/sachet), L. plantarum CECT 4528 (5×109 CFU/sachet), Bifidobacterium animalis subsp. lactis Bi1 LMG P-17502 (10×109 CFU/sachet), B. breve Bbr8 LMG P-17501 (10×109 CFU/sachet), B. breve Bl10 LMG P-17500 (10×109 CFU/sachet)14 weeksIBS–QoLWithout effect
Aroniadis et al., 2019 (USA)RCTIBS4518-65
Int: 33 (27-48)
Plac: 42 (28-48)
25 capsules perday
0.38 g minimally
Processed donor whole stool per capsule12 weeksIBS–QoLWithout effect
Šmid et al., 2016 (Slovenia–Croatia)RCTIBS7618-65(1.8×107 CFU/g) and
(2.5×107 CFU/g)
Lactobacillus acidophilus La-5 (1.8×107 CFU/g) and Bifidobacterium animalis ssp. lactis BB-12 (2.5×107 CFU/g)
Streptococcus thermophilus
4 weeksIBS–QoLWithout effect
Dapoigny et al., 2012 (France)Randomized double-blind pilot studyIBS47Int: 46.1±11.3
Plac: 48.0±10.8
6×108 CFULactobacillus casei variety rhamnosus LCR354 weeksGIQLIWithout effect
Riezzo et al., 2019 (Italy)RCTFC5619-65
42.4±13.8
15 days: four tablets daily
Then: two tablets daily
One tablet=1×108 CFU
Lactobacillus reuteri (LR) DSM 17938105 daysPAC–QoLWithout effect
Dimidi et al., 2019 (UK)RCTConstipation7518-65
Int: 35 (12)
Plac: 31 (10)
1.5×1010 CFU/dayBifidobacterium lactis NCC28184 weeksPAC–QoLWithout effect
Ibarra et al., 2018 (France)RCTAdults with functional constipation22418-701×109 or 1×1010 CFUBifidobacterium animalis subsp. lactis HN01928 daysPAC-QoLWithout effect
Ding et al., 2016 (China)RCT (prospective)Slow transit constipation93Plac: 48.3±11.3
Int: 47.2±10.7
0.63 gBifid triple viable capsules (BIFICO) and 8 g of soluble dietary fiber12 weeksGIQLIPositive effect
Gomi et al., 2018 (Japan)RCTPatients with functional GI disorders7920-64
Int: 41.1±10.1
Plac: 41.6±9.9
YIT 10347=3×107 CFU/mL
Streptococcus thermophilus YIT 2021=1×107
Bifidobacterium bifidum YIT 10347
Streptococcus thermophilus YIT 2021 (in both Plac and Int groups)
4 weeksSF-36 v2Without effect
Theodoropoulos et al., 2016 (Netherlands)RCTColectomy for cancer67Int: 66.8±2.17
Plac: 69±1.37
Sachets
12 g
Pediococcus pentosaceus 5-33:3, Leuconostoc mesenteroides 32-77:1, Lactobacillus paracasei ssp. paracasei 19, and L. plantarum 2362 and 2.5 g of each of the four fermentable fibers (prebiotics): b-glucan, inulin, pectin, and resistant starch15 daysGIQLI and EORTC QLQ-C30Without effect
Macnaughtan et al., 2020 (UK)RCTCirrhosis92 (68)18-786.5×109 CFULactobacillus casei Shirota (LcS)3 times per day for 6 monthsSF-36Without effect
Ahmadipour et al., 2020 (Iran)RCTInfant colic7221-90 days old
Int: 52.20±41.885 days
Plac: 49.36±23.321 days
5 drops of Pedilact
109 CFU
Lactobacillus rhamnosus, L. reuteri, Bifidobacterium infantis probiotics and fructooligosaccharide28 daysNot reportedWithout effect

RCT, randomized control trial; IBS, irritable bowel syndrome; FC, functional constipation; Int, intervention; Plac, placebo; CFU, colony forming unit; IBS-QoL, irritable bowel syndrome QoL; GIQLI, Gastrointestinal Quality of Life Index; PAC-QoL, Patient Assessment of Constipation QoL; SF-36, 36-item short form survey; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30.


Table 7 . Assessment of risk of bias for randomized and cross-over clinical trials using the Cochrane Risk of Bias 2 tool

ReferenceRisk domain
Bias arising from the randomization processBias because of deviations from the intended interventionMissing outcome dataBias in outcome measurementBias in the selection of reported resultsOverall risk of bias
Fujimori et al., 2009LowHighHighLowSome concernsHigh
Chen et al., 2016Some concernsLowHighLowSome concernsHigh
Ahmadipour et al., 2020Some concernsLowLowLowLowSome concerns
Macnaughtan et al., 2020LowLowLowLowLowLow
Lee et al., 2014LowLowHighLowLowHigh
Theodoropoulos et al., 2016LowLowLowLowLowLow
Golkhalkhali et al., 2018LowLowLowLowLowLow
Radvar et al., 2020LowLowLowLowLowLow
Ringel-Kulka et al., 2011LowLowLowLowLowLow
Gomi et al., 2018LowLowLowLowLowLow
Ding et al., 2016LowLowSome concernsLowLowSome concerns
Cudmore et al., 2017LowLowLowLowLowLow
Ibarra et al., 2018LowLowHighLowLowHigh
Dimidi et al., 2019LowLowLowLowLowLow
Kommers et al., 2019LowLowHighLowLowHigh
Riezzo et al., 2019Some concernsSome concernsSome concernsLowLowSome concerns
Olgac et al., 2020Some concernsHighSome concernsLowSome concernsHigh
Choi et al., 2011LowLowHighLowLowHigh
Dapoigny et al., 2012LowLowSome concernsLowSome concernsSome concerns
Cappello et al., 2013LowLowSome concernsLowSome concernsSome concerns
Lorenzo-Zúñiga et al., 2014LowLowSome concernsLowSome concernsSome concerns
Abbas et al., 2014LowLowSome concernsLowSome concernsSome concerns
Choi et al., 2015LowLowLowLowLowLow
Šmid et al., 2016LowLowLowLowLowLow
Nobutani et al., 2017Some concernsSome concernsLowLowSome concernsSome concerns
Pinto-Sanchez et al., 2017LowLowLowLowLowLow
Giannetti et al., 2017LowLowLowLowLowLow
Preston et al., 2018Some concernsLowLowLowLowSome concerns
Aroniadis et al., 2019LowLowHighLowLowHigh
Francavilla et al., 2019LowLowLowLowLowLow
Catinean et al., 2019Some concernsSome concernsLowLowSome concernsSome concerns
El-Salhy et al., 2020LowLowLowLowLowLow

Table 8 . Assessment of risk of bias for non-randomized clinical trials using the Cochrane Risk of Bias 2 tool

ReferenceRisk domain
Bias because of confoundingBias because of the selection of participantsBias in the classification of interventionBias because of deviations from the intended interventionBias because of missing outcome dataBias in outcome measurementBias in the selection of reported resultsOverall risk of bias
Drisko et al., 2006HighLowSome concernsLowSome concernsLowLowHigh
Xinias et al., 2018HighLowLowLowLowLowLowHigh
Ohigashi et al., 2011HighLowSome concernsLowSome concernsLowSome concernsHigh
Di Pierro et al., 2020HighLowLowLowLowLowLowHigh

Table 9 . Genus and species of probiotic supplementation in the included studies

GenusSpeciesStudies wherein probiotic supplements were effectiveStudies wherein probiotic supplements were ineffective
LactobacillusLactobacillus gasseriCappello et al., 2013Nobutani et al., 2017
Lactobacillus acidophilus1)Cappello et al., 2013, Kommers et al., 2019, Cudmore et al., 2017, Ringel-Kulka et al., 2011, Radvar et al., 2020, Golkhalkhali et al., 2018, Lee et al., 2014, Ohigashi et al., 2011Šmid et al., 2016
Lactobacillus plantarumLorenzo-Zúñiga et al., 2014, Cappello et al., 2013, Drisko et al., 2006, Cudmore et al., 2017, Theodoropoulos et al., 2016-
Lactobacillus casei1)Cappello et al., 2013, Drisko et al., 2006, Kommers et al., 2019, Radvar et al., 2020, Golkhalkhali et al., 2018Dapoigny et al., 2012, Macnaughtan et al., 2020
Lactobacillus salivariusCappello et al., 2013-
Lactobacillus sporogenesCappello et al., 2013-
Lactobacillus brevisDrisko et al., 2006-
Lactobacillus bulgaricusDrisko et al., 2006, Cudmore et al., 2017, Radvar et al., 2020-
Lactobacillus salivariusDrisko et al., 2006-
Lactobacillus rhamnosusDrisko et al., 2006, Cudmore et al., 2017, Radvar et al., 2020, Lee et al., 2014Ahmadipour et al., 2020
Lactobacillus reuteriOlgac et al., 2020Riezzo et al., 2019, Ahmadipour et al., 2020
Lactococcus lactisKommers et al., 2019, Golkhalkhali et al., 2018-
Lactobacillus paracaseiTheodoropoulos et al., 2016-
Leuconostoc mesenteroidesTheodoropoulos et al., 2016-
BifidobacteriumBifidobacterium bifidumDrisko et al., 2006, Kommers et al., 2019, Cudmore et al., 2017, Abbas et al., 2014Gomi et al., 2018
Bifidobacterium longum1)Cappello et al., 2013, Drisko et al., 2006, Radvar et al., 2020, Golkhalkhali et al., 2018, Di Pierro et al., 2020, Chen et al., 2016, Fujimori et al., 2009Ahmadipour et al., 2020
Bifidobacterium animalisCappello et al., 2013Šmid et al., 2016, Ibarra et al., 2018
Bifidobacterium lactisKommers et al., 2019, Xinias et al., 2018, Ringel-Kulka et al., 2011Dimidi et al., 2019
Bifidobacterium breveRadvar et al., 2020-
StreptococcusStreptococcus thermophilusDrisko et al., 2006, Radvar et al., 2020Šmid et al., 2016, Gomi et al., 2018
SaccharomycesSaccharomyces boulardiiAbbas et al., 2014, Choi et al., 2011-
BacillusBacillus subtilisChoi et al., 2015-
Bacillus nattoOhigashi et al., 2011-
EnterococcusEnterococcus faecalisChoi et al., 2015-
PediococcusPediococcus pentosaceusTheodoropoulos et al., 2016-
Pediococcus acidilacticiDrisko et al., 2006Ibarra et al., 2018
ClostridiumClostridium butyricumChen et al., 2016-

1)Lactobacillus and Bifidobacterium were the most common genera of probiotics that were used to study the effects of probiotic supplementation in clinical gastrointestinal investigations.

-, not available.


Table 10 . Notable outcomes of selected RCT studies assessing the effects of probiotics on GI diseases

ReferenceGut microbiota assessmentOutcomes of GI symptoms
Macnaughtan et al., 2020, UK--
Giannetti et al., 2017, Italy-In IBS, Bifidobacteria supplementation resulted in a complete resolution of abdominal pain in a significantly higher proportion of children
Cappello et al., 2013
Italy (Rome)
--
Cudmore et al., 2017, Ireland-Symptoms of constipation improved
Fujimori et al., 2009, Japan-Emotional function increased in the probiotic and synbiotic groups
Gomi et al., 2018, Japan-The YIT10347 group had significantly higher relief rates of overall gastrointestinal symptoms, upper gastrointestinal symptoms, flatus, and diarrhea than the placebo group
Francavilla et al., 2019, Italy·Using plate counts and 16S rRNA gene-based analysis
·Fecal samples (5 g) were mixed with 45 mL of sterilized physiological solution and homogenized. Viable bacterial cells were counted as described by De Angelis et al.
·To determine the identities of bacteria, sequences were first queried using a distributed BLASTn.NET algorithm24 against 16S bacterial sequences derived from NCBI.
-
Radvar et al., 2020, Iran-Body weight decreased in the synbiotic and placebo groups
Aroniadis et al., 2019, USA16S rRNA sequencing-
Chen et al., 2016, Taiwan-Complaints of abdominal pain, abdominal bloating, excessive passage of gas, foul smell of flatulence, belching, abdominal noises, and heartburn were significantly improved in the entire sample
Dapoigny et al., 2012, FranceExtraction of total bacterial DNA (QIAamp Fast DNA Stool Mini Kit, QIAGEN), the presence of Lactobacillus casei variety rhamnosus was specifically determined by qualitative polymerase chain reaction (PCR - primer pairs hyb-21) – cycles of amplification.A decrease in the abdominal pain severity score was observed with LCR35
Choi et al., 2015, Korea-The abdominal pain/discomfort score in treatment group 4 was more prominently improved compared with that of the placebo group
In patients with constipation-predominant IBS, the improvements in stool frequency and consistency were significantly higher in treatment groups 4 and 1, respectively, than those in the placebo group
There were more favorable tendencies of effects on bloating in all treatment groups than in the placebo group
El-Salhy et al., 2020, Norway16S rRNA gene sequencing-
Ding et al., 2016, China-During the intervention period, patients who were treated with the synbiotic exhibited increased stool frequency, improved stool consistency, decreased colonic transit time, and improved constipation-related symptoms
Ohigashi et al., 2011, Japan-Defecation frequency, anal pain, and Wexner score were significantly poorer in the rectal group than in the colonic group
Ringel-Kulka et al., 2011, USAQuantitative real-time polymerase chain reaction of fecal samplesAbdominal bloating improved in the probiotic group compared with the placebo group at 4 and 8 weeks
Dimidi et al., 2019, UKQuantitative polymerase chain reaction-
Šmid et al., 2016, Slovenia & Croatia-Significant improvements in bloating severity, satisfaction with bowel movements
Golkhalkhali et al., 2018, Malaysia-Nausea, vomiting, and diarrhea significantly improved in the treatment group
Theodoropoulos et al., 2016, Netherlands-Differences in the EORTC QLQ-C30 “diarrhea” domain score from baseline were better after synbiotic administration after 3 (P=0.04) and 6 months (P=0.003)
Nobutani et al., 2017, Japan·Purified DNA was used as a template for the following two-step polymerase chain reaction.
·Fecal microbiota was measured using fecal bacterial 16S rDNA V4-V6 region-targeted pyrosequencing.
CP2305 favorably changed the fecal characteristics compared with placebo among patients with IBS with either diarrhea or constipation subtypes
Drisko et al., 2006, USA-Significant improvements in pain were observed (P=0.05)

RCT, randomized controlled trial; GI, gastrointestinal; IBS, irritable bowel syndrome; NCBI, National Center for Biotechnology Information; QoL, quality of life; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer’s 30-item QoL questionnaire version 30; -, not available.


References

  1. Abbas Z, Yakoob J, Jafri W, Ahmad Z, Azam Z, Usman MW, et al. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial. Eur J Gastroenterol Hepatol. 2014. 26:630-639.
    Pubmed CrossRef
  2. Ahmadipour S, Fallahi A, Rahmani P. Probiotics for infantile colic. Clin Nutr Exp. 2020. 31:1-7.
    Pubmed CrossRef
  3. Amitay EL, Carr PR, Gies A, Laetsch DC, Brenner H. Probiotic/synbiotic treatment and postoperative complications in colorectal cancer patients: Systematic review and meta-analysis of randomized controlled trials. Clin Transl Gastroenterol. 2020. 11:e00268.
    Pubmed KoreaMed CrossRef
  4. Aragon G, Graham DB, Borum M, Doman DB. Probiotic therapy for irritable bowel syndrome. Gastroenterol Hepatol. 2010. 6:39-44.
    Pubmed KoreaMed
  5. Arco S, Saldaña E, Serra-Prat M, Palomera E, Ribas Y, Font S, et al. Functional constipation in older adults: Prevalence, clinical symptoms and subtypes, association with frailty, and impact on quality of life. Gerontology. 2022. 68:397-406.
    Pubmed CrossRef
  6. Aroniadis OC, Brandt LJ, Oneto C, Feuerstadt P, Sherman A, Wolkoff AW, et al. Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2019. 4:675-685.
    Pubmed CrossRef
  7. Aziz Q, Doré J, Emmanuel A, Guarner F, Quigley EM. Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motil. 2013. 25:4-15.
    Pubmed CrossRef
  8. Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017. 312:G52-G62.
    Pubmed KoreaMed CrossRef
  9. Bron PA, Kleerebezem M, Brummer RJ, Cani PD, Mercenier A, MacDonald TT, et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr. 2017. 117:93-107.
    Pubmed KoreaMed CrossRef
  10. Bultman SJ. Emerging roles of the microbiome in cancer. Carcinogenesis. 2014. 35:249-255.
    Pubmed KoreaMed CrossRef
  11. Cani PD. Gut microbiota-at the intersection of everything? Nat Rev Gastroenterol Hepatol. 2017. 14:321-322.
    CrossRef
  12. Cappello C, Tremolaterra F, Pascariello A, Ciacci C, Iovino P. A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life. Int J Colorectal Dis. 2013. 28:349-358.
    Pubmed KoreaMed CrossRef
  13. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012. 24:521-e248.
    Pubmed KoreaMed CrossRef
  14. Catinean A, Neag AM, Nita A, Buzea M, Buzoianu AD. Bacillus spp. spores-a promising treatment option for patients with irritable bowel syndrome. Nutrients. 2019. 11:1968.
    CrossRef
  15. Cha BK, Jung SM, Choi CH, Song ID, Lee HW, Kim HJ, et al. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: A randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2012. 46:220-227.
    Pubmed CrossRef
  16. Chen JC, Lee WJ, Tsou JJ, Liu TP, Tsai PL. Effect of probiotics on postoperative quality of gastric bypass surgeries: a prospective randomized trial. Surg Obes Relat Dis. 2016. 12:57-61.
    Pubmed CrossRef
  17. Chmielewska A, Szajewska H. Systematic review of randomised controlled trials: Probiotics for functional constipation. World J Gastroenterol. 2010. 16:69-75.
    Pubmed KoreaMed CrossRef
  18. Choi CH, Kwon JG, Kim SK, Myung SJ, Park KS, Sohn CI, et al. Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double-blind, placebo-controlled, multicenter, phase II trial. Neurogastroenterol Motil. 2015. 27:705-716.
    Pubmed CrossRef
  19. Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ. A randomized, double-blind, placebo-controlled multicenter trial of saccharomyces boulardii in irritable bowel syndrome: Effect on quality of life. J Clin Gastroenterol. 2011. 45:679-683.
    Pubmed CrossRef
  20. Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci. 2011. 108:4586-4591.
    Pubmed KoreaMed CrossRef
  21. Codling C, O'Mahony L, Shanahan F, Quigley EM, Marchesi JR. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci. 2010. 55:392-397.
    Pubmed CrossRef
  22. Cudmore S, Doolan A, Lacey S, Shanahan F. A randomised, double-blind, placebo-controlled clinical study: the effects of a synbiotic, Lepicol, in adults with chronic, functional constipation. Int J Food Sci Nutr. 2017. 68:366-377.
    Pubmed CrossRef
  23. Dapoigny M, Piche T, Ducrotte P, Lunaud B, Cardot JM, Bernalier-Donadille A. Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: A randomized, double-blind study. World J Gastroenterol. 2012. 18:2067-2075.
    Pubmed KoreaMed CrossRef
  24. Dazıroğlu MEÇ, Yıldıran H. Intestinal dysbiosis and probiotic use: its place in hepatic encephalopathy in cirrhosis. Ann Gastroenterol. 2023. 36:141-148.
    Pubmed KoreaMed CrossRef
  25. de Oliveira GLV, Leite AZ, Higuchi BS, Gonzaga MI, Mariano VS. Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology. 2017. 152:1-12.
    Pubmed KoreaMed CrossRef
  26. Di Pierro F, Bergomas F, Marraccini P, Ingenito MR, Ferrari L, Vigna L. Pilot study on non-celiac gluten sensitivity: effects of Bifidobacterium longum ES1 co-administered with a gluten-free diet. Minerva Gastroenterol Dietol. 2020. 66:187-193.
    Pubmed CrossRef
  27. Didari T, Mozaffari S, Nikfar S, Abdollahi M. Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis. World J Gastroenterol. 2015. 21:3072-3084.
    Pubmed KoreaMed CrossRef
  28. Dimidi E, Zdanaviciene A, Christodoulides S, Taheri S, Louis P, Duncan PI, et al. Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation. Aliment Pharmacol Ther. 2019. 49:251-264.
    Pubmed CrossRef
  29. Ding C, Ge X, Zhang X, Tian H, Wang H, Gu L, et al. Efficacy of synbiotics in patients with slow transit constipation: a prospective randomized trial. Nutrients. 2016. 8:605.
    Pubmed KoreaMed CrossRef
  30. Distrutti E, Salvioli B, Azpiroz F, Malagelada JR. Rectal function and bowel habit in irritable bowel syndrome. Am J Gastroenterol. 2004. 99:131-137.
    Pubmed CrossRef
  31. Drisko J, Bischoff B, Hall M, McCallum R. Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. J Am Coll Nutr. 2006. 25:514-522.
    Pubmed CrossRef
  32. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016. 150:1262-1279.
    Pubmed CrossRef
  33. El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020. 69:859-867.
    Pubmed KoreaMed CrossRef
  34. Faith JJ, McNulty NP, Rey FE, Gordon JI. Predicting a human gut microbiota's response to diet in gnotobiotic mice. Science. 2011. 333:101-104.
    Pubmed KoreaMed CrossRef
  35. Ferrario C, Taverniti V, Milani C, Fiore W, Laureati M, De Noni I, et al. Modulation of fecal Clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults. J Nutr. 2014. 144:1787-1796.
    Pubmed CrossRef
  36. Francavilla R, Piccolo M, Francavilla A, Polimeno L, Semeraro F, Cristofori F, et al. Clinical and microbiological effect of a multispecies probiotic supplementation in celiac patients with persistent IBS-type symptoms: A randomized, double-blind, placebo-controlled, multicenter trial. J Clin Gastroenterol. 2019. 53:e117-e125.
    Pubmed KoreaMed CrossRef
  37. Fujimori S, Gudis K, Mitsui K, Seo T, Yonezawa M, Tanaka S, et al. A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition. 2009. 25:520-525.
    Pubmed CrossRef
  38. Fuller R, Gibson GR. Probiotics and prebiotics: microflora management for improved gut health. Clin Microbiol Infect. 1998. 4:477-480.
    CrossRef
  39. Giamarellos-Bourboulis E, Tang J, Pyleris E, Pistiki A, Barbatzas C, Brown J, et al. Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol. 2015. 50:1076-1087.
    Pubmed CrossRef
  40. Giannetti E, Maglione M, Alessandrella A, Strisciuglio C, De Giovanni D, Campanozzi A, et al. A mixture of 3 bifidobacteria decreases abdominal pain and improves the quality of life in children with irritable bowel syndrome: A multicenter, randomized, double-blind, placebo-controlled, crossover trial. J Clin Gastroenterol. 2017. 51:e5-e10.
    Pubmed CrossRef
  41. Golkhalkhali B, Rajandram R, Paliany AS, Ho GF, Wan Ishak WZ, Johari CS, et al. Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial. Asia Pac J Clin Oncol. 2018. 14:179-191.
    Pubmed CrossRef
  42. Gomi A, Yamaji K, Watanabe O, Yoshioka M, Miyazaki K, Iwama Y, et al. Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: A double-blind, randomized, placebo-controlled study. J Dairy Sci. 2018. 101:4830-4841.
    Pubmed CrossRef
  43. Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012. 491:254-258.
    Pubmed KoreaMed CrossRef
  44. Guinane CM, Cotter PD. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol. 2013. 6:295-308.
    Pubmed KoreaMed CrossRef
  45. Hajjar J, Mendoza T, Zhang L, Fu S, Piha-Paul SA, Hong DS, et al. Associations between the gut microbiome and fatigue in cancer patients. Sci Rep. 2021. 11:5847.
    Pubmed KoreaMed CrossRef
  46. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011. 343:d5928.
    CrossRef
  47. Hollister EB, Cain KC, Shulman RJ, Jarrett ME, Burr RL, Ko C, et al. Relationships of microbiome markers with extraintestinal, psychological distress and gastrointestinal symptoms, and quality of life in women with irritable bowel syndrome. J Clin Gastroenterol. 2020. 54:175-183.
    Pubmed KoreaMed CrossRef
  48. Hoveyda N, Heneghan C, Mahtani KR, Perera R, Roberts N, Glasziou P. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol. 2009. 9:15.
    Pubmed KoreaMed CrossRef
  49. Hungin AP, Mulligan C, Pot B, Whorwell P, Agréus L, Fracasso P, et al; European Society for Primary Care Gastroenterology. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice-an evidence-based international guide. Aliment Pharmacol Ther. 2013. 38:864-886.
    CrossRef
  50. Ibarra A, Latreille-Barbier M, Donazzolo Y, Pelletier X, Ouwehand AC. Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: A double-blind, randomized, placebo-controlled, and dose-ranging trial. Gut Microbes. 2018. 9:236-251.
    Pubmed KoreaMed CrossRef
  51. Irwin C, Khalesi S, Cox AJ, Grant G, Davey AK, Bulmer AC, et al. Effect of 8-weeks prebiotics/probiotics supplementation on alcohol metabolism and blood biomarkers of healthy adults: a pilot study. Eur J Nutr. 2018. 57:1523-1534.
    Pubmed CrossRef
  52. Jafari T, Mahmoodnia L, Tahmasebi P, Memarzadeh MR, Sedehi M, Beigi M, et al. Effect of cumin (Cuminum cyminum) essential oil supplementation on metabolic profile and serum leptin in pre-diabetic subjects: A randomized double-blind placebo-controlled clinical trial. J Funct Food. 2018. 47:416-422.
    CrossRef
  53. Jeffery IB, O'Toole PW, Öhman L, Claesson MJ, Deane J, Quigley EM, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012. 61:997-1006.
    Pubmed CrossRef
  54. Kataoka K. The intestinal microbiota and its role in human health and disease. J Med Invest. 2016. 63:27-37.
    Pubmed CrossRef
  55. Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, et al. A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2003. 17:895-904.
    Pubmed CrossRef
  56. Kommers MJ, Silva Rodrigues RA, Miyajima F, Zavala Zavala AA, Ultramari VRLM, Fett WCR, et al. Effects of probiotic use on quality of life and physical activity in constipated female university students: A randomized, double-blind placebo-controlled study. J Altern Complement Med. 2019. 25:1163-1171.
    Pubmed CrossRef
  57. Koretz RL. Probiotics in gastroenterology: How pro is the evidence in adults? Am J Gastroenterol. 2018. 113:1125-1136.
    Pubmed CrossRef
  58. Lee JY, Chu SH, Jeon JY, Lee MK, Park JH, Lee DC, et al. Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: A double-blind, randomized, placebo-controlled trial. Dig Liver Dis. 2014. 46:1126-1132.
    Pubmed CrossRef
  59. Lin DC. Probiotics as functional foods. Nutr Clin Pract. 2003. 18:497-506.
    Pubmed CrossRef
  60. Lorenzo-Zúñiga V, Llop E, Suárez C, Alvarez B, Abreu L, Espadaler J, et al. I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life. World J Gastroenterol. 2014. 20:8709-8716.
    Pubmed KoreaMed CrossRef
  61. López-Moreno A, Suárez A, Avanzi C, Monteoliva-Sánchez M, Aguilera M. Probiotic strains and intervention total doses for modulating obesity-related microbiota dysbiosis: A systematic review and meta-analysis. Nutrients. 2020. 12:1921.
    Pubmed KoreaMed CrossRef
  62. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016. 375:2369-2379.
    Pubmed CrossRef
  63. Macnaughtan J, Figorilli F, García-López E, Lu H, Jones H, Sawhney R, et al. A double-blind, randomized placebo-controlled trial of probiotic Lactobacillus casei Shirota in stable cirrhotic patients. Nutrients. 2020. 12:1651.
    Pubmed KoreaMed CrossRef
  64. Maharshak N, Ringel Y, Katibian D, Lundqvist A, Sartor RB, Carroll IM, et al. Fecal and mucosa-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 2018. 63:1890-1899.
    Pubmed CrossRef
  65. Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005. 40:540-551.
    Pubmed CrossRef
  66. Marteau P, Pochart P, Bouhnik Y, Rambaud JC. The fate and effects of transiting, nonpathogenic microorganisms in the human intestine. World Rev Nutr Diet. 1993. 74:1-21.
    Pubmed CrossRef
  67. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006. 101:812-822.
    Pubmed CrossRef
  68. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008. 14:2650-2661.
    Pubmed KoreaMed CrossRef
  69. McKean J, Naug H, Nikbakht E, Amiet B, Colson N. Probiotics and subclinical psychological symptoms in healthy participants: A systematic review and meta-analysis. J Altern Complement Med. 2017. 23:249-258.
    Pubmed CrossRef
  70. Merkel IS, Locher J, Burgio K, Towers A, Wald A. Physiologic and psychologic characteristics of an elderly population with chronic constipation. Am J Gastroenterol. 1993. 88:1854-1859.
    Pubmed
  71. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011. 105:755-764.
    Pubmed CrossRef
  72. Miller LE, Zimmermann AK, Ouwehand AC. Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit. World J Gastroenterol. 2016. 22:5122-5131.
    Pubmed KoreaMed CrossRef
  73. Ng SC, Lam EF, Lam TT, Chan Y, Law W, Tse PC, et al. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol. 2013. 28:1624-1631.
    Pubmed CrossRef
  74. Nobutani K, Sawada D, Fujiwara S, Kuwano Y, Nishida K, Nakayama J, et al. The effects of administration of the Lactobacillus gasseri strain CP2305 on quality of life, clinical symptoms and changes in gene expression in patients with irritable bowel syndrome. J Appl Microbiol. 2017. 122:212-224.
    Pubmed CrossRef
  75. Norton C. Constipation in older patients: effects on quality of life. Br J Nurs. 2006. 15:188-192.
    Pubmed CrossRef
  76. O'Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology. 2005. 128:541-551.
    Pubmed CrossRef
  77. Ohigashi S, Hoshino Y, Ohde S, Onodera H. Functional outcome, quality of life, and efficacy of probiotics in postoperative patients with colorectal cancer. Surg Today. 2011. 41:1200-1206.
    Pubmed CrossRef
  78. Olgac A, Sezer OB, Hosnut FO, Ozcay F. Lactobacillus reuteri DSM 17938 and quality of life associated with functional constipation. Slov Med J. 2020. 89:347-356.
    CrossRef
  79. Parkes GC, Brostoff J, Whelan K, Sanderson JD. Gastrointestinal microbiota in irritable bowel syndrome: Their role in its pathogenesis and treatment. Am J Gastroenterol. 2008. 103:1557-1567.
    Pubmed CrossRef
  80. Pimentel M, Lembo A. Microbiome and its role in irritable bowel syndrome. Dig Dis Sci. 2020. 65:829-839.
    Pubmed CrossRef
  81. Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017. 153:448-459.e8.
    Pubmed CrossRef
  82. Ponnusamy K, Choi JN, Kim J, Lee SY, Lee CH. Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J Med Microbiol. 2011. 60:817-827.
    Pubmed KoreaMed CrossRef
  83. Preston K, Krumian R, Hattner J, de Montigny D, Stewart M, Gaddam S. Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 improve quality-of-life and IBS symptoms: a double-blind, randomised, placebo-controlled study. Benef Microbes. 2018. 9:697-706.
    Pubmed CrossRef
  84. Quigley EM. Probiotics and irritable bowel syndrome. Biosci Microflora. 2009. 27:119-124.
    CrossRef
  85. Radvar FF, Mohammad-Zadeh M, Mahdavi R, Andersen V, Nasirimotlagh B, Faramarzi E, et al. Effect of synbiotic supplementation on matrix metalloproteinase enzymes, quality of life and dietary intake and weight changes in rectal cancer patients undergoing neoadjuvant chemoradiotherapy. Mediterr J Nutr Metab. 2020. 13:1-11.
    CrossRef
  86. Riezzo G, Chimienti G, Orlando A, D'Attoma B, Clemente C, Russo F. Effects of long-term administration of Lactobacillus reuteri DSM-17938 on circulating levels of 5-HT and BDNF in adults with functional constipation. Benef Microbes. 2019. 10:137-147.
    Pubmed CrossRef
  87. Ringel-Kulka T, Palsson OS, Maier D, Carroll I, Galanko JA, Leyer G, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: A double-blind study. J Clin Gastroenterol. 2011. 45:518-525.
    Pubmed KoreaMed CrossRef
  88. Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One. 2012. 7:e34938.
    Pubmed KoreaMed CrossRef
  89. Shanahan F. The colonic microbiota in health and disease. Curr Opin Gastroenterol. 2013. 29:49-54.
    Pubmed CrossRef
  90. Shivaji UN, Ford AC. Prevalence of functional gastrointestinal disorders among consecutive new patient referrals to a gastroenterology clinic. Frontline Gastroenterol. 2014. 5:266-271.
    Pubmed KoreaMed CrossRef
  91. Šmid A, Strniša L, Bajc K, Vujić-Podlipec D, Matijašić BB, Rogelj I. Randomized clinical trial: The effect of fermented milk with the probiotic cultures Lactobacillus acidophilus La-5® and Bifidobacterium BB-12® and Beneo dietary fibres on health-related quality of life and the symptoms of irritable bowel syndrome in adults. J Funct Foods. 2016. 24:549-557.
    CrossRef
  92. Staudacher HM, Lomer MCE, Farquharson FM, Louis P, Fava F, Franciosi E, et al. A diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and a probiotic restores Bifidobacterium species: A randomized controlled trial. Gastroenterology. 2017. 153:936-947.
    Pubmed CrossRef
  93. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015. 48:258-264.
    Pubmed CrossRef
  94. Theodoropoulos GE, Memos NA, Peitsidou K, Karantanos T, Spyropoulos BG, Zografos G. Synbiotics and gastrointestinal function-related quality of life after elective colorectal cancer resection. Ann Gastroenterol. 2016. 29:56-62.
    Pubmed KoreaMed
  95. Tlaskalova-Hogenova H, Vannucci L, Klimesova K, Stepankova R, Krizan J, Kverka M. Microbiome and colorectal carcinoma: Insights from germ-free and conventional animal models. Cancer J. 2014. 20:217-224.
    Pubmed CrossRef
  96. Towers AL, Burgio KL, Locher JL, Merkel IS, Safaeian M, Wald A. Constipation in the elderly: Influence of dietary, psychological, and physiological factors. J Am Geriatr Soc. 1994. 42:701-706.
    Pubmed CrossRef
  97. Waitzberg DL, Quilici FA, Michzputen S, Friche Passos Mdo C. The effect of probiotic fermented milk that includes Bifidobacterium lactis CNCM I-2494 on the reduction of gastrointestinal discomfort and symptoms in adults: a narrative review. Nutr Hosp. 2015. 32:501-509.
    Pubmed CrossRef
  98. Whelan K, Quigley EM. Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease. Curr Opin Gastroenterol. 2013. 29:184-189.
    Pubmed CrossRef
  99. Wong RK, Yang C, Song GH, Wong J, Ho KY. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: A randomized double-blinded placebo study. Dig Dis Sci. 2015. 60:186-194.
    Pubmed CrossRef
  100. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011. 334:105-108.
    Pubmed KoreaMed CrossRef
  101. Xinias I, Analitis A, Mavroudi A, Roilides I, Lykogeorgou M, Delivoria V, et al. A synbiotic infant formula with high magnesium content improves constipation and quality of life. Pediatr Gastroenterol Hepatol Nutr. 2018. 21:28-33.
    Pubmed KoreaMed CrossRef