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Fig. 2 | Journal of Biomedical Science

Fig. 2

From: Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Fig. 2

Proposed schema of early pathophysiological changes in epithelial barrier defects and bacterial invasiveness, which causes microbiota dysbiosis and chronic inflammation. The proposed common ground hypothesis depicting the early abnormality of leaky gut that drives microbiota dysbiosis would lead to chronic inflammation. The hypothesis is that endogenous and exogenous factors that trigger gut barrier impairment and low grade immune activation could impose selective pressure on the intestinal microbiota. The subclinical mucosal abnormalities which developed in individuals with genetic predisposition then favor the growth of opportunistic microbes for conversion to pathobionts. The pathobionts subsequently aggravate morphologic and functional changes in gut tissues and remote organs with pathological consequences, and result in chronic inflammation and clinical symptoms. Further postulation with a detailed focus on the gut barriers are added here. We speculate that the initial epithelial barrier dysfunction manifested by transcellular hyperpermeability and passive bacterial internalization may instigate a selection pressure on microbiota (such as positive inforcement by anchorage and growth advantage, and negative impediment by aerotolerance and immune evasion), leading to the emergence of invasive virulent pathobionts. The selection pressure and mucosal pathobionts may cause a shift in the fecal microbial community. On the host’s side, bacterial internalization may also cause epithelial cytoskeletal disorganization and paracellular TJ destruction. The combination of broken epithelial barrier and invasive pathobionts results in a massive amount of bacterial translocation, which leads to clinical features of morphological damage and chronic inflammation. Additional evidence also showed that chronic inflammation may impact on the gut microbiota and cause epithelial death-dependent barrier loss, which eventually leads to vicious cycles of uncontrollable colitis

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