Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding Microbiota-derived indoles, particularly indole-3-lactic acid (ILA), play a key role in protecting against intestinal inflammation and restoring microbial balance. Lactobacillus produces ILA by metabolizing tryptophan, which enhances the expression of enzymes involved in tryptophan metabolism, leading to the synthesis of other indole derivatives, including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). These indole derivatives reduce intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10-/- colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria and enhances the production of IPA and IAA. Microbial cross-feeding mediated by ILA is microbiota-dependent and enhances indole production under conditions of dysbiosis, but not in microbiota disruption with antibiotics. The anti-inflammatory effects of IPA are regulated by PXR activation, while those of IAA are microbiota-dependent. These findings suggest that microbiota-derived indoles mediate inter-microbial communication and cooperatively control intestinal homeostasis. The study highlights the potential of microbiota-derived metabolites or targeted "postbiotics" as interventions for dysbiosis-driven diseases. Keywords: Microbial tryptophan metabolites, Indole derivatives, Intestinal inflammation, Lactobacillus.Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding Microbiota-derived indoles, particularly indole-3-lactic acid (ILA), play a key role in protecting against intestinal inflammation and restoring microbial balance. Lactobacillus produces ILA by metabolizing tryptophan, which enhances the expression of enzymes involved in tryptophan metabolism, leading to the synthesis of other indole derivatives, including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). These indole derivatives reduce intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10-/- colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria and enhances the production of IPA and IAA. Microbial cross-feeding mediated by ILA is microbiota-dependent and enhances indole production under conditions of dysbiosis, but not in microbiota disruption with antibiotics. The anti-inflammatory effects of IPA are regulated by PXR activation, while those of IAA are microbiota-dependent. These findings suggest that microbiota-derived indoles mediate inter-microbial communication and cooperatively control intestinal homeostasis. The study highlights the potential of microbiota-derived metabolites or targeted "postbiotics" as interventions for dysbiosis-driven diseases. Keywords: Microbial tryptophan metabolites, Indole derivatives, Intestinal inflammation, Lactobacillus.