Tryptophan is a key amino acid in the human diet that is broken down by gut microorganisms, which convert it into multiple metabolites that have various effects on human health. A recent study published in the journal Nature Microbiology examines tryptophan metabolism in response to increased dietary fiber intake.
Study: Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota. Image Credit: Tatjana Baibakova / Shutterstock.com
Tryptophan metabolism in the gut
In the gastrointestinal tract, tryptophan is broken down into indole, indole lactic acid (ILA), or indole propionic acid (IPA). High indole levels are associated with chronic kidney disease, whereas ILA has protective effects against dietary allergies. IPA is inversely associated with type 2 diabetes and has been shown to benefit gut mucosal integrity and reduce the risk of atherosclerosis.
Other tryptophan metabolites maintain epithelial barriers and immunologic function, regulate inflammation and key metabolic pathways, and provide protection against infectious disease. Conversely, some molecules, like indole, are metabolized by the liver into a toxin that accumulates in chronic kidney disease, subsequently exacerbating the condition. High gut indole levels also increase the risk of persistent Clostridiodes difficile infection of the colon.
Indole is the most abundant tryptophan metabolite in humans and mice, as it comprises up to 75% of all tryptophan metabolites. Multiple microorganisms catabolize tryptophan to indole through tryptophanase or to ILA/IPA through other pathways.
Several studies have suggested the benefits of dietary fiber in reducing protein breakdown into toxic byproducts by colon microbes. Dietary fiber also increases food transit through the gut, which increases the availability of carbohydrates in the colon, ultimately preventing protein catabolism.
Recent studies have indicated a potential association between fermentable fiber intake and tryptophan metabolism. The current experimental study seeks to explore the role of fermentable carbohydrates on tryptophan metabolism in the gut.
About the study
The researchers conducted in vitro and in vivo mouse experiments to evaluate competition between gut microbes for tryptophan as a substrate and its metabolic end-products.
C. sporogenes, P. anaerobius, B. thetaiotaomicron, and E. coli were selected as representative bacterial strains to study the gut microbiome in an artificial in vitro environment. These findings were then compared with experiments performed using complex microbial communities isolated from human feces samples.
What did the study show?
In the three-community model, both in vivo and in vitro experiments showed that E. coli competed with C. Sporogenes to metabolize tryptophan. E. coli produces indole, whereas C. sporogenes produces ILA and IPA.
Supplementation with carbohydrates, even at low concentrations, inhibits E. coli tryptophanase activity by two to fourfold, subsequently reducing indole production. C. sporogenes did not use carbohydrates, even when supplemented with five—to ten-fold glucose concentrations, thus indicating its preference for amino acids.
These findings indicate that the competition between E. coli and C. sporogenes is influenced by carbohydrate availability in the growth medium rather than the abundance of tryptophan-metabolizing bacteria.
While simple sugars in the diet do not reach the colon, they are derived from the breakdown of dietary fiber. When pectin, a complex carbohydrate, was added to the growth medium, Bacteroides thetaiotamicron broke down pectin into simple sugars, thereby cross-feeding E. coli.
Pectin supplementation upregulated E. coli genes, regulating the utilization of fiber degradation products by 16- to 64-fold. This led to lower indole levels without any change in E. coli abundance, as E. coli exhibited a preference for simple sugars as compared to tryptophan.
While the abundance of C. sporogenes decreased with pectin consumption, ILA and IPA levels increased as more tryptophan became available to C. sporogenes. Moreover, the inhibition of indole production significantly increased available tryptophan for other metabolic pathways in the gut.
Human fecal cultures showed similar phenomena, thus supporting the observation that indole levels decline with increased dietary fiber intake. When fecal microbiota was transplanted to gnotobiotic mice, the results were similar, demonstrating that dietary fiber suppresses indole production by multiple gut species.
Implications for human health
Our findings explain why consumption of fermentable fibres suppresses indole production but promotes the generation of other tryptophan metabolites associated with health benefits.”
The availability of microbial substrates and fermentable carbohydrates in the gut affects the direction of tryptophan metabolism. As a result, the relative abundances of tryptophan metabolites are altered through their effects on specific bacterial species.
The study findings have profound implications for dietary recommendations aimed at improving gut health and preventing the development of metabolic disorders. Increased consumption of fermentable fibers may lead to a shift in gut microbial metabolism that increases the production of metabolites that support the integrity of the gut mucosa, immunity, and metabolic health.
Journal reference:
- Sinha, A. K., Laursen, M. F., Brinck, J. E., et al. (2024). Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota. Nature Microbiology. doi:10.1038/s41564-024-01737-3.