Multi-Omics Analysis of the Gut-Liver Axis Reveals the Mechanism of Liver Injury in Colitis Mice.

Luoyi Zhu,Zeqing Lu,Jie Fu,Xin Zong,Mingliang Jin,Yuanzhi Cheng,Xiao Xiao,Yizhen Wang,Fengqin Wang

doi:10.3389/fimmu.2021.773070

Abstract

Liver injury is a common complication of inflammatory bowel disease (IBD). However, the mechanisms of liver injury development are not clear in IBD patients. Gut microbiota is thought to be engaged in IBD pathogenesis. Here, by an integrated analysis of host transcriptome and colonic microbiome, we have attempted to reveal the mechanism of liver injury in colitis mice. In this study, dextran sulfate sodium (DSS) -induced mice colitis model was constructed. Liver transcriptome showed significant up- and down-regulation of pathways linked to immune response and lipid metabolism, respectively. Whilst the colon transcriptome exhibited dramatic alterations in immune response and pathways associated with cell growth and death. The microbiota of DSS-treated mice underwent strong transitions. Correlation analyses identified genes associated with liver and colon injury, whose expression was associated with the abundance of liver and gut health-related bacteria. Collectively, the results indicate that the liver injury in colitis mice may be related to the intestinal dysbiosis and host-microbiota interactions. These findings may provide new insights for identifying potential targets for the treatment of IBD and its induced liver injury.

Highlights

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) is a chronic intestine inflammatory disease characterized by low mortality and intractable cure [1]
Our results showed severe intestinal histological damage and disruption of the structural integrity of tight junctions (TJs) in the dextran sulfate sodium (DSS) group, which further indicated that DSS successfully induced colitis
It was reported that Tchol and low-density lipoprotein (LDL) levels were lower in inflammatory bowel disease (IBD) patients compared to healthy subjects, which is contrary to the findings of this study

Summary

Introduction

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) is a chronic intestine inflammatory disease characterized by low mortality and intractable cure [1]. Of even greater concern is that IBD increases the risk of multiple complications [3, 4]. Liver Injury in Colitis Mice provide a positive effect on human and animal health as well as social development. The development of complications may further aggravate the treatment difficulty and health risk, and yet the underlying molecular mechanisms and therapeutic targets of IBD-induced liver disease are still inadequately characterized. Transcriptomic technologies are widely used in the fields of clinical diagnosis and drug development due to their usefulness in revealing the molecular mechanisms of specific biological processes and disease development through understanding gene function and gene structure [10, 11]. Transcriptome sequencing analysis of liver at risk from colitis is beneficial to uncover the underlying mechanisms of its pathogenesis

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Conclusion