pH regulates gut bacterial tryptophan metabolism

Area of Science:

• Microbiology
• Human Physiology
• Metabolomics

Background:

• Intestinal pH is a key factor affecting gut microbiota composition and activity.
• Gut bacteria metabolize tryptophan into various compounds, including indole, indolelactic acid (ILA), and indolepropionic acid (IPA).
• Indole is a precursor to indoxyl sulfate (IS), linked to chronic kidney disease (CKD), while ILA and IPA possess beneficial health effects.

Purpose of the Study:

• To investigate the influence of intestinal pH on microbial tryptophan metabolite production.
• To explore the relationship between fecal pH, tryptophan metabolites, and their health implications, particularly in relation to CKD.

Main Methods:

• Analysis of fecal pH and tryptophan metabolites in two human cohorts.
• In vitro fermentation experiments using E. coli and C. sporogenes at varying pH levels.
• Human fecal cultures to assess pH-dependent gene expression and metabolite production.

Main Results:

• Positive correlations were observed between fecal pH, indole, and urinary IS.
• Negative correlations were found between fecal pH and beneficial metabolites ILA and IPA.
• Low pH (5.5) inhibited E. coli indole production and repressed the tnaA gene, while enhancing beneficial metabolite production by C. sporogenes.

Conclusions:

• Intestinal pH acts as a critical regulator of gut bacterial tryptophan metabolism.
• Modulating intestinal pH presents a potential therapeutic avenue for managing CKD by altering the balance of gut microbial metabolites.