Methyl indole-3-acetate contributes to strain-specific anti-inflammatory effects of Lactiplantibacillus plantarum
Abstract
Lactiplantibacillus plantarum is a widely recognized probiotic with anti-inflammatory potential, yet its efficacy varies among strains and the underlying determinants remain poorly defined. Here, we identify methyl indole-3-acetate (MIA), a previously uncharacterized microbial metabolite, as a contributor to the strain-specific anti-inflammatory effects of L. plantarum . Strains with higher MIA production show stronger protection against colitis in mice, whereas deletion of the key biosynthetic enzyme eliminates this protective effect. Mechanistically, MIA epigenetically activates the transcription of lncRNA Snhg9 by promoting histone H4K8 acetylation at its promoter, an effect mediated through direct inhibition of HDAC1. In turn, Snhg9 suppresses NF-κB signaling by enhancing the deacetylase activity of SIRT1, thereby attenuating inflammatory responses. Together, our findings support a role for MIA in shaping strain-dependent host responses to L. plantarum , uncover a lncRNA-mediated host–microbe regulatory pathway, and provide a framework for further investigation of strain-specific probiotic function in inflammatory disorders.
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Authors: Kailin Liu, Meng Wang, Xinyi Zhu, Libin Pan, Lichao Wang, Wu Bao, Bingqing Hang, Xianjiong Chen, Guifang Li, Daqian Xu, Dong Guo, Yinan Shen, Gaopeng Li, Yuan Ding, Honglin An, Yanan Zhang, Shu Zhu, Juan Du, Qiming Liang, Wangyun Xu, Bin Huang, Jiaxin Chen, Ping Li, Yuhao Wang
Institutions: First Affiliated Hospital Zhejiang University, Shanghai Jiao Tong University, Zhejiang University, Second Affiliated Hospital of Zhejiang University, Zhejiang Cancer Hospital, Zhejiang Gongshang University, Tata Institute of Fundamental Research, Fujian University of Traditional Chinese Medicine, Cancer Hospital of Chinese Academy of Medical Sciences, Institute of Immunology, Beike Biotechnology (China)