Environmental pH regulates tryptophan metabolism in human gut microbes

Julius Emil Brinck*, Martin Frederik Laursen, Henrik Roager, Anurag Kumar Sinha, Tine Rask Licht

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

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Purpose: Microbial tryptophan (Trp) catabolism in the gut results in the generation of multiple metabolites, exerting either beneficial or harmful effects on host health. For example, gut bacteria can metabolize Trp into indole, which contributes to the progression of chronic kidney disease, or into indolelactic acid (ILA) and indolepropionic acid (IPA), associated with positive health outcomes. Human studies have indicated links between fecal pH and microbiota-derived Trp metabolites; however, the mechanistic regulation of the production is largely unknown. We aimed to explore the effect of environmental pH on bacterial Trp metabolism.

Methods: The effect of pH on bacterial Trp metabolism was assessed by culturing E. coli, a primary producer of intestinal indole, and Clostridium sporogenes, which produces ILA- and IPA, in chemostats at different constant pH, either in monoculture or in defined community experiments. Liquid chromatography-high resolution mass spectrometry (LC-HR-MS) was done to identify the metabolites. Additionally, fecal samples from healthy humans were collected, fecal pH were measured and Trp metabolites were quantified.

Results: Results from in vitro experiments showed that pH significantly affected Trp utilization and indole production by E. coli, whereas pH did not directly influence the generation of IPA by C. sporogenes. Moreover, using a continuous co-culture of both species, we revealed that low pH inhibits Trp utilization and indole production by E. coli, thereby allowing more Trp available to C. sporogenes towards the production of high IPA levels. In contrast, high pH stimulated Trp utilization and indole production by E. coli, thus strongly inhibiting IPA production by C. sporogenes. Total bacterial cell counts showed that pH alterations influenced the relative metabolite production by regulating corresponding metabolic pathways rather than altering bacterial abundance. Corroborating our in vitro findings, we found that the levels of ILA and IPA are negatively associated with pH in human fecal samples. 

Conclusions: We present mechanistic explanations for how pH in the gut regulates microbial Trp metabolic pathways. Environmental pH alterations shift the metabolic profile of Trp towards indole at high pH or towards health beneficial Trp metabolites at low pH.
Original languageEnglish
Title of host publicationThe Danish Microbiological Society Annual Congress 2023 : Abstract book
Number of pages1
PublisherDanish Microbiological Society
Publication date2023
Article number7
Publication statusPublished - 2023
EventThe Danish Microbiological Society Annual Congress 2023 - Copenhagen, Denmark
Duration: 13 Nov 202313 Nov 2023


ConferenceThe Danish Microbiological Society Annual Congress 2023


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