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Human gut-associated Bifidobacterium species salvage exogenous indole, a uremic toxin precursor, to synthesize indole-3-lactic acid via tryptophan.

Authors :
Yong CC
Sakurai T
Kaneko H
Horigome A
Mitsuyama E
Nakajima A
Katoh T
Sakanaka M
Abe T
Xiao JZ
Tanaka M
Odamaki T
Katayama T
Source :
Gut microbes [Gut Microbes] 2024 Jan-Dec; Vol. 16 (1), pp. 2347728. Date of Electronic Publication: 2024 May 05.
Publication Year :
2024

Abstract

Indole in the gut is formed from dietary tryptophan by a bacterial tryptophan-indole lyase. Indole not only triggers biofilm formation and antibiotic resistance in gut microbes but also contributes to the progression of kidney dysfunction after absorption by the intestine and sulfation in the liver. As tryptophan is an essential amino acid for humans, these events seem inevitable. Despite this, we show in a proof-of-concept study that exogenous indole can be converted to an immunomodulatory tryptophan metabolite, indole-3-lactic acid (ILA), by a previously unknown microbial metabolic pathway that involves tryptophan synthase β subunit and aromatic lactate dehydrogenase. Selected bifidobacterial strains converted exogenous indole to ILA via tryptophan (Trp), which was demonstrated by incubating the bacterial cells in the presence of (2- <superscript>13</superscript> C)-labeled indole and l-serine. Disruption of the responsible genes variedly affected the efficiency of indole bioconversion to Trp and ILA, depending on the strains. Database searches against 11,943 bacterial genomes representing 960 human-associated species revealed that the co-occurrence of tryptophan synthase β subunit and aromatic lactate dehydrogenase is a specific feature of human gut-associated Bifidobacterium species, thus unveiling a new facet of bifidobacteria as probiotics. Indole, which has been assumed to be an end-product of tryptophan metabolism, may thus act as a precursor for the synthesis of a host-interacting metabolite with possible beneficial activities in the complex gut microbial ecosystem.

Details

Language :
English
ISSN :
1949-0984
Volume :
16
Issue :
1
Database :
MEDLINE
Journal :
Gut microbes
Publication Type :
Academic Journal
Accession number :
38706226
Full Text :
https://doi.org/10.1080/19490976.2024.2347728