Table. 1.

Table. 1. Table 1

Characteristics of the included studies

Reference	Study type	Subject/disease	Host	Expressed protein (location)	Substrate to by-product(s)/promoter(s) and its inducer	Result
Jiang et al., 2023	Experimental mouse model	Pah^F263S PKU mouse/PKU	EcN	PAL (bacterial surface)	Phe to TCA/PheP and PAL	Compared to control EcN, serum Phe was reduced by 44.4%
Puurunen et al., 2021	Double-blinded RCT (phase 1/2a)	Human/PKU patients and adult healthy volunteers	EcN	PAL (intracellular) and LAAD (bacterial surface)	Phe to TCA and PP/PheP and PAL	The engineered EcN was well tolerated with a maximum dose of 2×10¹¹ CFU Adverse events were mostly GIT problems Dose-responsive increases in TCA and hippuric acid
Ochoa-Sanchez et al., 2021	Experimental rat model	Rat/BDL rat	EcN	Ammonia consuming enzymes argA215 and synthesize butyrate (intracellular)	Ammonia to L-Arg/PfnrS	The EP attenuated hyperammonemia
Kurtz et al., 2019	Experimental mouse model	OTC-deficient mouse and TAC liver-injured mouse/hyperammonemia	EcN	L-Arg biosynthetic enzyme argA215 (intracellular)	Ammonia to L-Arg/PfnrS	Decreased hyperammonemia and improved survival in OTC-deficient mice Reduced hyperammonemia in the TAC liver-injured mice
	Double-blinded RCT (phase 1)	Human/adult healthy volunteers	EcN	L-Arg biosynthetic enzyme argA215 (intracellular)	Ammonia to L-Arg/PfnrS	Daily doses of up to 1.5×10¹² CFU are well tolerated for up to 14 days Increased in urinary nitrate, plasma ¹⁵N-nitrate, and urinary ¹⁵N-nitrate
Isabella et al., 2018	Experimental mouse model	Pah^enu2/enu2 PKU mouse/PKU	EcN	PAL (intracellular) and LAAD (bacterial surface)	Phe to TCA and PP/PheP and PAL	Compared to the control group blood Phe was reduced by 38%
	Experimental monkey model	Cynomolgus monkey/no disease	EcN	PAL (intracellular) and LAAD (bacterial surface)	Phe to TCA and PP/PheP and PAL	Inhibition of Phe increment after an oral Phe challenge
Durrer et al., 2017	Experimental mouse model	Pah^enu2/enu2 PKU mouse/PKU	Lactobacillus reuteri	PAL (intracellular)	Phe to TCA/constitutive Promoter	Serum Phe significantly reduced compared to the control group
Nicaise et al., 2008	Experimental rat and mouse models	OTC-deficient mouse, TAC liver-injured mouse and CCL4 liver-injured rat/hyperammonemia	Lactobacillus plantarum	Ala dehydrogenase (intracellular)	Ammonia to Ala/NR	In all three models, intervention with the Engineered L. plantarum significantly decreased serum ammonia. Also in acute liver injury model the EP significantly extend the lifespan

PKU, phenylketonuria; EcN, Escherichia coli Nissle 1917; PAL, phenylalanine ammonia-lyase; TCA, trans-cinnamic acid; Phe, phenylalanine; RCT, randomized controlled trial; LAAD, L-amino acid deaminase; CFU, colony-forming unit; GIT, gastrointestinal tract; BDL, bile-duct-ligated; Arg, arginine; EP, engineered probiotic; OTC, ornithine transcarbamylase; TAC, thioacetamide; PP, phenylpyruvate; CCL4, carbon tetrachloride; Ala, alanine; NR, not reported.

Prev Nutr Food Sci 2024;29:1~7 https://doi.org/10.3746/pnf.2024.29.1.1