Gut Bacteria Team Up to Convert Fiber Into a Key Longevity Metabolite

Indole-3-propionate (IPA) is a tryptophan-derived gut metabolite with wide-ranging health benefits, including maintaining intestinal barrier integrity, exerting antioxidant effects, and modulating anti-inflammatory signaling. Low IPA levels have been consistently linked to inflammatory bowel disease, type 2 diabetes, colorectal cancer, and multiple sclerosis. Despite its importance, the precise gut bacteria responsible for IPA production — and how diet modulates them — have remained poorly understood.

To address this gap, ETH Zürich researchers cultured fecal microbiota from 16 healthy adults anaerobically in 96-deepwell plates, supplementing each sample with tryptophan and one of eight distinct dietary fibers (arabinogalactan, inulin, beta-glucan, pectin, pea fiber, xylan, resistant dextrin, or soluble starch). Tryptophan-derived indoles — including indole, indole-3-acetate (IAA), indole-3-lactate (ILA), and IPA — were quantified by UHPLC-DAD, and microbial community shifts were tracked via 16S rRNA gene amplicon sequencing.

IPA production varied dramatically by donor and was most strongly promoted by pectin, followed by soluble starch, resistant dextrin, arabinogalactan, beta-glucan, and pea fiber. Crucially, IPA elevation was not linked to any previously known IPA-producing Clostridium or Peptostreptococcus species. Instead, community analyses pointed to Lachnospira eligens, a pectin-degrading bacterium, as the key associated taxon. Pure culture experiments confirmed that L. eligens produces ILA — but not IPA — from tryptophan, identifying it as a novel ILA producer.

When the team supplemented fecal cultures from six additional donors with exogenous ILA rather than tryptophan, IPA production was consistently observed, confirming ILA as an effective IPA precursor in complex communities. Screening of 17 candidate pure strains then identified Enterocloster aldenensis as a novel IPA producer — but only when provided with ILA, not tryptophan directly. Co-culture of L. eligens and E. aldenensis together produced IPA from tryptophan, demonstrating a two-step cross-feeding mechanism: L. eligens converts tryptophan to ILA, which E. aldenensis then reduces to IPA.

These findings reframe our understanding of tryptophan metabolism in the gut. Rather than a single organism completing the full reductive pathway, IPA production appears to emerge from microbial cooperation — a cross-feeding interaction that may explain why known IPA producers are often absent in studies showing elevated IPA. The work also highlights pectin as a particularly promising prebiotic for promoting this beneficial metabolic axis, opening doors for precision dietary strategies to support gut and systemic health.