Tryptophan is an important amino acid in the human diet that is broken down by gut bacteria and converted into multiple metabolites with various effects on human health. A recent study published in Nature Microbiology investigated tryptophan metabolism with increasing dietary fiber intake.
Study: Dietary fiber induces microbial tryptophan metabolism via metabolic interactions in the gut microbiota. Image credit: Tatjana Baibakova / Shutterstock.com
Intestinal tryptophan metabolism
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, ILA has a protective effect against food allergies, IPA is inversely correlated with type 2 diabetes, and has been shown to benefit intestinal mucosal integrity and reduce the risk of atherosclerosis.
Other tryptophan metabolites maintain epithelial barrier and immune function, regulate inflammation and key metabolic pathways, and provide defense against infection. Conversely, some molecules, such as indole, are metabolized in the liver to toxins that accumulate in chronic kidney disease and subsequently worsen the pathology. High indole concentrations in the gut also increase the risk of persisting colonic Clostridiodes difficile infection.
Indole is the most abundant tryptophan metabolite in humans and mice, accounting for up to 75% of total tryptophan metabolites. Several microorganisms can degrade tryptophan to indole via tryptophanase or to ILA/IPA via other pathways.
Some studies suggest that dietary fiber may help reduce the breakdown of proteins into toxic by-products by colonic microorganisms. Dietary fiber also facilitates the passage of food through the intestine, increases carbohydrate availability in the colon, and ultimately prevents protein catabolism.
Recent studies have demonstrated a potential link between fermentable fiber intake and tryptophan metabolism. Current experimental studies seek to explore the role of fermentable carbohydrates on intestinal tryptophan metabolism.
About the Research
The researchers performed in vitro and in vivo mouse experiments to evaluate gut bacteria's competition for the substrate tryptophan and its metabolic end products.
C. sporogenes, P. anaerobius, B. thetaiotaomicron, and E. coli were selected as representative bacterial strains to study the gut microbiota in an artificial in vitro environment, and these results were then compared with experiments performed using a complex microbial community isolated from human fecal samples.
What did the study find?
In the three community model, both in vivo and in vitro experiments showed that E. coli competes with C. sporogenes to metabolize tryptophan, with E. coli producing indole and C. sporogenes producing ILA and IPA.
Supplementation with low concentrations of carbohydrate inhibited E. coli tryptophanase activity by 2-4 fold, reducing indole production, and C. sporogenes did not use carbohydrates even when supplemented with 5-10 fold higher concentrations of glucose, indicating a preference for amino acids.
These results indicate that competition between E. coli and C. sporogenes is influenced by the availability of carbohydrates in the growth medium and not by the abundance of tryptophan-metabolizing bacteria.
Simple sugars in the diet do not reach the colon, but are produced by the breakdown of dietary fiber. When the complex carbohydrate pectin was added to the growth medium, B. thetaiotamicron broke pectin down into simple sugars, thereby feeding E. coli.
Pectin supplementation upregulated E. coli genes and modulated utilization of fiber breakdown products by 16-64 fold, and, because E. coli prefers simple sugars over tryptophan, there was no change in E. coli populations and a decrease in indole concentrations.
Pectin intake reduced the number of C. sporogenes but increased the levels of ILA and IPA as tryptophan availability to C. sporogenes increased. Furthermore, inhibition of indole production significantly increased tryptophan available for other metabolic pathways in the gut.
A similar phenomenon was observed in human fecal cultures, supporting the observation that indole levels decreased with increasing dietary fiber intake. Similar results were obtained when fecal microbiota were transplanted into gnotobiotic mice, demonstrating that dietary fiber suppresses indole production by multiple gut bacterial species.
Effects on human health
Our findings explain why consumption of fermentable fiber suppresses the production of indole but promotes the production of other tryptophan metabolites that are associated with health benefits.”
The availability of microbial substrates and fermentable carbohydrates in the gut influences the direction of tryptophan metabolism, thereby altering the relative abundance of tryptophan metabolites through their effects on specific bacterial species.
The findings have profound implications for dietary recommendations aimed at improving gut health and preventing the development of metabolic disorders: Increasing fermentable fiber intake may alter gut microbial metabolism and increase the production of metabolites that support intestinal mucosal integrity, immune, and metabolic health.
Journal References:
Sinha, AK, Laursen, MF, Brinck, JE, et al. (2024). Dietary fiber induces microbial tryptophan metabolism through metabolic interactions in the gut microbiota. Nature Microbiology. doi:10.1038/s41564-024-01737-3.
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