Alistipes putredinis CCUG 45780T exacerbates DSS-induced colitis in mice via modulation of gut microbiota and succinate metabolism.

BACKGROUND

Alistipes is a relatively new genus in the phylum Bacteroidetes, and its role in UC remains unclear. Among its members, Alistipes putredinis is particularly prominent. In this study, we investigated the effects of Alistipes putredinis CCUG 45780T on colitis using both in vitro and in vivo experiments, aiming to provide a theoretical basis for understanding the contribution of gut microbiota to UC pathogenesis.

RESULTS

Whole-genome sequencing of Alistipes putredinis CCUG 45780ᵀ revealed 13 virulence genes and 11 resistance genes. Targeted metabolomic analysis identified 9 metabolites significantly increased in the bacterial culture supernatant, among which only succinate exhibited proinflammatory effects. Oral administration of Alistipes putredinis CCUG 45780ᵀ did not cause overt pathogenicity in healthy mice but significantly exacerbated DSS-induced colitis, as indicated by weight loss, elevated disease activity index (DAI) scores, colon shortening, and aggravated mucosal damage. This was accompanied by markedly increased expression of TNF-α, IL-1β, IL-6, and NLRP3. Moreover, treatment altered the gut microbial community, increasing Bacteroidetes abundance while reducing Actinobacteria and Lactobacillus, elevated colonic succinate levels, and upregulated SUCNR1 expression. Collectively, these findings suggest that Alistipes putredinis CCUG 45780ᵀ aggravates colitis through microbiota modulation and succinate-mediated inflammation.

CONCLUSION

Alistipes putredinis CCUG 45780ᵀ exacerbates DSS-induced colitis in mice, likely through gut microbiota dysregulation and succinate-driven inflammatory pathways.