Lactobacillus intestinalis-derived indole-3-propionic acid mediates benefits of maternal tryptophan metabolism on offspring intestinal health

The intestinal microbiota has critical roles in the host's metabolism. We found the tryptophan (Trp) metabolites were different between germ-free (GF) and specific pathogen-free (SPF) animals, including pigs and mice. For example, Trp catabolism and indole-3-propionic acid (IPA) biosynthesis were disrupted in GF animals. We also found IPA production was decreased in antibiotic-treated animals, such as penicillin-administrated pigs and colistin, metronidazole, or vancomycin-treated mice. These data indicated that gut microbiota absence or perturbation would lead to Trp metabolism disruption, which might further affect the host's health and disease. Penicillin and its derivatives are most frequently used in pregnancy; thus, we sought to expose mother mice to subtherapeutic levels of penicillin in gestation or/and lactation to investigate the antibiotic's effect on mice Trp metabolism and its transgenerational impact. The results showed that even a low degree of antibiotic expose could perturb Trp metabolism and IPA production in both dams and pups. We further analyzed the gut microflora community in dams and pups and found Lactobacillus intestinalis (L. intestinalis) was decreased under antibiotics administration and mostly positively associated with IPA. L. intestinalis was incubated with tryptophan derivatives to explore if it was IPA producer or not. We found L. intestinalis could produce IPA when incubated with IA, which might be catalyzed by aryl-CoA dehydrogenase and associated with the GM000249 gene. L. intestinalis colonization could promote IPA production and further promote antibiotic-induced colitis susceptibility in mother and offspring mice.