Wang Wenxue, Liu Zhongjian, Yue Wei, Zhu Ling, Zhong Huijie, Yang Chao, He Tian, Wan Ping, Geng Jiawei
Department of Infectious Disease and Hepatic Disease, First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
School of Medicine, Kunming University of Science and Technology, Kunming, China.
Front Microbiol. 2022 May 26;13:875238. doi: 10.3389/fmicb.2022.875238. eCollection 2022.
Both bacteria and autophagy are implicated in inflammatory bowel disease (IBD) pathogenesis. However, how bacteria crosstalk with autophagy signaling remains largely known, especially in intestinal mucosa. This study aimed to profile the internal complex autophagy signaling cascade and their external correlation with these bacteria, and consequently provide a systematic and precise target for future IBD diagnosis and therapy. We found the Ulcerative colitis (UC) patients exhibited more severe dysbiosis than the Crohn's disease (CD) patients, as represented by alpha diversity, community phenotypes, and functional annotation compared with the control population. Meanwhile, CD patients showed greater transcriptional signaling activities of autophagy, endoplasmic reticulum (ER) stress, and bile acid production. Dominant bacteria (e.g., , , , and ) were positively correlated and low-abundance bacteria (e.g., , , , and ) were negatively correlated with the autophagy signaling cascade (184 autophagy genes, 52 ER stress genes, and 22 bile acid production genes). Our observations suggested UC patients showed temporary and widespread microbiota turbulence and CD patients showed processive and local autophagy activity during IBD progression. Intestinal mucosa-colonizing bacteria were correlated with the bile/ER stress/autophagy signaling axis in IBD pathogenesis.
细菌和自噬均与炎症性肠病(IBD)的发病机制有关。然而,细菌如何与自噬信号相互作用在很大程度上仍不清楚,尤其是在肠道黏膜中。本研究旨在剖析内部复杂的自噬信号级联及其与这些细菌的外部相关性,从而为未来IBD的诊断和治疗提供系统而精确的靶点。我们发现,与对照人群相比,溃疡性结肠炎(UC)患者的菌群失调比克罗恩病(CD)患者更为严重,这体现在α多样性、群落表型和功能注释方面。同时,CD患者的自噬、内质网(ER)应激和胆汁酸生成的转录信号活性更高。优势菌(如 、 、 和 )与自噬信号级联(184个自噬基因、52个ER应激基因和22个胆汁酸生成基因)呈正相关,而低丰度菌(如 、 、 和 )与自噬信号级联呈负相关。我们的观察结果表明,在IBD进展过程中,UC患者表现出暂时且广泛的微生物群紊乱,而CD患者表现出进行性和局部的自噬活性。肠道黏膜定植菌与IBD发病机制中的胆汁/ER应激/自噬信号轴相关。