Enriched Streptococcus alactolyticus in non-cub giant panda gut contributes to the regulation of tryptophan and its neuromodulatory derivatives

Despite feeding on a high-lignocellulose bamboo diet, the giant panda (Ailuropoda melanoleuca) retains a typical gut microbiome of Carnivora. We conducted shotgun metagenomic sequencing and functional validation of the giant panda's gut microbiome to elucidate its physiological roles and explore its functional adaptation to the species' specialized diet. Our results revealed that Streptococcus alactolyticus significantly increased in the guts of subadult, adult, and elderly individuals versus that in cubs. The gut microbiome of these non-cub giant pandas was significantly enriched in pathways and modules associated with tryptophan biosynthesis. Whole-genome sequencing and in vitro fermentation of S. alactolyticus demonstrated its ability to biosynthesize tryptophan. Gavage of S. alactolyticus in mice led to the enrichment of aromatic amino acid metabolism pathways in gut microbiome, accompanied by significantly elevated levels of 5-hydroxyindole acetic acid and kynurenine in fecal and/or serum samples (p < 0.05). Transcriptome sequencing of colons from mice revealed that most significant upregulated Gene Ontology (GO) terms mainly were related to spindle checkpoint signaling and chromosome segregation, while most significant downregulated GO terms mainly involved synaptic functional regulation. These findings suggest that S. alactolyticus enriched in the non-cub giant panda gut can regulate tryptophan, influencing host gut physiology via tryptophan metabolites.