The findings, published in Gut Microbes, highlight the potential of targeted dietary interventions to promote beneficial gut taxa and metabolites, according to the researchers from ETH Zürich and Eawag in Switzerland.
Tryptophan-derived indoles are compounds that have been associated with the health and balance of the gastrointestinal tract. The study noted that reduced IPA levels have been linked to inflammatory bowel disease, type 2 diabetes and colorectal cancer.
Since fiber-rich diets can promote IPA, the researchers set out to evaluate the effects of different fiber types and identify IPA-producing taxa in fecal samples from healthy individuals.
“These findings highlight the potential of dietary fibers, particularly pectin, to enhance IPA production in the gut microbiota, with ILA [indole-3-lactate] cross-feeding as a possible underlying mechanism,” the researchers wrote.
A double-edged sword
The essential amino acid tryptophan can be catabolized by gut bacteria into indole and indole derivatives.
Research indicates that more than 85 kinds of gram-negative and gram-positive bacteria convert around 4% to 6% of tryptophan to indoles in the colon. The compounds play an important biological role in human health and homeostasis, but scientists acknowledge that many questions remain unanswered.
While they may support intestinal health, regulate aspects of immunity and have been linked to lower risks of some diseases such as periodontitis, dementia and metabolic syndrome, indoles are considered a “double-edged sword” because of the potential toxic effects of some derivatives, such as indoxyl sulfate, which may contribute to the development of chronic kidney disease.
However, indole derivatives such as IPA and ILA may have numerous beneficial effects.
“They [IPA and ILA] have been reported to influence local and systemic processes and play a role in maintaining intestinal barrier integrity, modulate mucin production, exert antioxidant effects and orchestrate anti-inflammatory signaling through host receptors,” the researchers wrote.
“In turn, decreased indoles have been associated with inflammatory bowel diseases as well as type 2 diabetes, colon cancer and multiple sclerosis, among others.”
Study details
The researchers cultured fecal microbiota from 16 adults with tryptophan and eight different dietary fibers, including starch, xylan, dextrin, pectin, pea, inulin, beta-glucan and arabinogalactan from larch wood.
They monitored the effects using 16S rRNA gene amplicon sequencing and liquid chromatography with diode array detection.
The results revealed that the concentrations and types of indoles produced by the bacteria were specific to the donors, with pectin strongly promoting IPA production in some donors.
“IPA production was not associated with any known IPA producer but with the pectin-utilizing species Lachnospira eligens, which produced indole-3-lactate (ILA) in vitro, the IPA precursor,” the researchers wrote.
When they supplemented ILA in six additional fecal cultures, they noted its effectiveness as a substrate for IPA production. They also identified “a novel IPA producer, Enterocloster aldenensis, which produced IPA exclusively from ILA but not from tryptophan.”
“Co-culture of L. eligens and E. aldenensis resulted in IPA production, providing new evidence for an ILA cross-feeding mechanism that may contribute to the IPA-promoting effects observed with pectin,” the study noted, calling for future animal and human studies to expand upon these findings.
Source: Gut Microbes, 17(1), doi: 10.1080/19490976.2025.2501195; “Novel cross-feeding human gut microbes metabolizing tryptophan to indole-3-propionate.” Authors: J.N. Zund et al.