Dietary fibre influences microbial tryptophan metabolism through metabolic interactions in the gut microbiota. Tryptophan is metabolized by gut microbes into various compounds, some beneficial and others harmful. This study shows that dietary fibre reduces indole production, which is linked to chronic kidney disease, while promoting the production of beneficial metabolites like indole-lactic acid (ILA) and indolepropionic acid (IPA). The research used in vitro and animal experiments to examine how microbial competition for tryptophan and the resulting metabolites are influenced by dietary fibre. In a three-species defined community, Escherichia coli (indole producer) and Clostridium sporogenes (ILA/IPA producer) competed for tryptophan. However, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli, which inhibited indole production through catabolite repression, making more tryptophan available to C. sporogenes and increasing ILA and IPA production. This effect was confirmed in human faecal cultures and gnotobiotic mice. Tryptophan is metabolized by gut microbes into various compounds, including indole, ILA, and IPA, which have different effects on host health. Indole is associated with chronic kidney disease, while ILA and IPA are beneficial. The study found that dietary fibre reduces indole production by inhibiting the tnaA gene in E. coli, which is responsible for indole production. This allows more tryptophan to be used by other microbes, such as C. sporogenes, for Stickland fermentation, leading to increased production of ILA and IPA. The study also showed that dietary fibre, such as pectin, inhibits indole production in the gut microbiota of both mice and humans. This is due to cross-feeding of monosaccharides from pectin degradation to E. coli, which represses tnaA gene expression and reduces indole production. The findings suggest that dietary fibre can be used to shift gut microbial tryptophan metabolism towards beneficial metabolites like ILA and IPA, rather than harmful ones like indole. The study highlights the importance of microbial metabolic interactions in determining the production of tryptophan metabolites and their impact on host health.Dietary fibre influences microbial tryptophan metabolism through metabolic interactions in the gut microbiota. Tryptophan is metabolized by gut microbes into various compounds, some beneficial and others harmful. This study shows that dietary fibre reduces indole production, which is linked to chronic kidney disease, while promoting the production of beneficial metabolites like indole-lactic acid (ILA) and indolepropionic acid (IPA). The research used in vitro and animal experiments to examine how microbial competition for tryptophan and the resulting metabolites are influenced by dietary fibre. In a three-species defined community, Escherichia coli (indole producer) and Clostridium sporogenes (ILA/IPA producer) competed for tryptophan. However, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli, which inhibited indole production through catabolite repression, making more tryptophan available to C. sporogenes and increasing ILA and IPA production. This effect was confirmed in human faecal cultures and gnotobiotic mice. Tryptophan is metabolized by gut microbes into various compounds, including indole, ILA, and IPA, which have different effects on host health. Indole is associated with chronic kidney disease, while ILA and IPA are beneficial. The study found that dietary fibre reduces indole production by inhibiting the tnaA gene in E. coli, which is responsible for indole production. This allows more tryptophan to be used by other microbes, such as C. sporogenes, for Stickland fermentation, leading to increased production of ILA and IPA. The study also showed that dietary fibre, such as pectin, inhibits indole production in the gut microbiota of both mice and humans. This is due to cross-feeding of monosaccharides from pectin degradation to E. coli, which represses tnaA gene expression and reduces indole production. The findings suggest that dietary fibre can be used to shift gut microbial tryptophan metabolism towards beneficial metabolites like ILA and IPA, rather than harmful ones like indole. The study highlights the importance of microbial metabolic interactions in determining the production of tryptophan metabolites and their impact on host health.