Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis
Journal
Journal of Biomedical Science
Journal Volume
25
Journal Issue
1
Pages
79
Date Issued
2018
Author(s)
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as colitis-associated cancers. Genetic polymorphism of innate immune receptors had long been considered a major risk factor for IBD, and the mutations were also recently observed in CRC. Altered microbial composition (termed microbiota dybiosis) and dysfunctional gut barrier manifested by epithelial hyperpermeability and high amount of mucosa-associated bacteria were observed in IBD and CRC patients. The findings suggested that aberrant immune responses to penetrating commensal microbes may play key roles in fueling disease progression. Accumulative evidence demonstrated that mucosa-associated bacteria harbored colitogenic and protumoral properties in experimental models, supporting an active role of bacteria as pathobionts (commensal-derived opportunistic pathogens). Nevertheless, the host factors involved in bacterial dysbiosis and conversion mechanisms from lumen-dwelling commensals to mucosal pathobionts remain unclear. Based on the observation of gut leakiness in patients and the evidence of epithelial hyperpermeability prior to the onset of mucosal histopathology in colitic animals, it was postulated that the epithelial barrier dysfunction associated with mucosal enrichment of specific bacterial strains may predispose the shift to disease-associated microbiota. The speculation of leaky gut as an initiating factor for microbiota dysbiosis that eventually led to pathological consequences was proposed as the "common ground hypothesis", which will be highlighted in this review. Overall, the understanding of the core interplay between gut microbiota and epithelial barriers at early subclinical phases will shed light to novel therapeutic strategies to manage chronic inflammatory disorders and colitis-associated cancers. ? 2018 The Author(s).
Subjects
bacterial internalization; barrier function; Colitis; colorectal cancers; epithelial permeability; intestinal dysbiosis
SDGs
Other Subjects
Bacteroides; Bacteroides fragilis; biofilm; cancer risk; carcinogenesis; chronic inflammation; colorectal cancer; common ground hypothesis; disease predisposition; dysbiosis; Enterococcus; Escherichia coli; Fusobacterium nucleatum; host pathogen interaction; human; hypothesis; immune response; inflammatory bowel disease; intestine flora; intestine mucosa permeability; nonhuman; pathogenesis; permeability barrier; priority journal; Review; animal; colorectal tumor; dysbiosis; genetics; immunology; inflammatory bowel disease; innate immunity; intestine flora; microbiology; mouse; physiology; Animals; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Immunity, Innate; Inflammatory Bowel Diseases; Mice
Publisher
BioMed Central Ltd.
Type
review