Abstract Background Crohn’s disease (CD) is a common autoimmune disease. α4β7 integrin antagonists can significantly improve the treatment status of CD patients, but there are still problems of no response and loss of response to treatment. Therefore, it is urgent to explore the response mechanism of α4β7 integrin antagonists in the treatment of CD at present. Methods This project conducts research from multiple aspects such as clinical, cellular and animal levels. Firstly, clinical specimens of CD patients are collected to verify the changes of specific intestinal flora L.reuteri, lactation modification levels and Tfh/Tfr differentiation levels after treatment with α4β7 integrin antagonists. Secondly, a humanized mouse enteritis model is established. It was proved that L.reuteri affected the response of CD to α4β7 integrin antagonists by altering the Tfh/Tfr balance. Finally, the related mechanism of the L.reuteri-mediated lactation modification pathway regulating the Tfh/Tfr cell balance was explored. Results The proportion of L.reuteri in the remission group of CD patients treated with α4β7 integrin antagonists increased significantly. Meanwhile, the results of metagenomic analysis showed that the abundance of L.reuteri was related to the treatment response level of CD. The results of cell co-culture indicated that the increase in the abundance of L.reuteri would promote lactation modification at the H3K9la site of histone. Moreover, lactation modification can promote the balance of Tfh/Tfr, thereby increasing the therapeutic response level of CD to α4β7 integrin antagonists. Conclusion Changes in the composition of the intestinal microbiota, especially the increase in the abundance of L.reuteri, can mediate the regulation of Tfh/Tfr balance by H3K9la lactation modification, thereby enhancing the therapeutic response level of CD to α4β7 integrin antagonists. Conflict of interest: Ms. Kang, Mei: No conflict of interest Han, Bing: No conflict of interest Wen, Hongtao: No conflict of interest Li, Ya: No conflict of interest
Kang et al. (Thu,) studied this question.