Indole-3-acetic acid alleviates DSS-induced colitis by promoting the production of R-equol from Bifidobacterium pseudolongum

ABSTRACT

Background

Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.

Method

C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics.

Result

In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice.

Conclusion

Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

KEYWORDS:

• IAA
• regulatory T cells
• gut microbiome
• bifidobacterium pseudolongum
• colitis

Acknowledgments

We appreciate Xiang Zhou for advice on histopathology.

Disclosure statement

No potential conflict of interest was reported by the author (s).

Ethics approval and consent to participate

Animal experiments were conducted in accordance with the Institutional Animal Care and Use Committee of Capital Medical University, and were performed in accordance with the ARRIVE guidelines.

Supplementary material

_{Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2329147.}

Additional information

Funding

This work was supported by National Natural Science Foundation of China [Grant no. 82300733]; National Natural Science Foundation of China [Grant no. 82330017]; National Natural Science Foundation of China [Grant no. 81930015] and Golden Seed Research Fund [Grant no. CYJZ202222].