5-Aminosalicylic acid alters the gut microbiota and altered microbiota transmitted vertically to offspring have protective effects against colitis

Autor: Haruka Wada, Jun Miyoshi, Satoshi Kuronuma, Yuu Nishinarita, Noriaki Oguri, Noritaka Hibi, Osamu Takeuchi, Yoshihiro Akimoto, Sonny T. M. Lee, Minoru Matsuura, Taku Kobayashi, Toshifumi Hibi, Tadakazu Hisamatsu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-39491-x
Popis: Abstract Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.
Databáze: Directory of Open Access Journals
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