Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 22, Issue 40, Pages 6058-6075Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612822666160914182822
Keywords
Microbiota; microbiome; leaky gut; intestinal permeability; autoimmunity; inflammation
Categories
Funding
- NHMRC [1059660]
- Conselho de Desenvolvimento Cientifico e Tecnologico (CNPq
- Brazil)
- EC [613979]
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Background: In steady state conditions intestinal immune homeostasis is maintained by a sophisticated bidirectional dialogue between the microbiota and the intestinal immune system. This cross talk is enabled by the presence of highly adapted secretory cells, sampling cells and pattern recognition receptors in the gastric epithelium. Methods: Herein we discuss the mechanisms involved in the breakdown of intestinal homeostasis and the development of systemic immune activation and neuroinflammation with a view to discussing the importance of these processes, in tandem with genetic and environmental factors, in the pathophysiology of (auto) immune diseases. Data is presented explaining how immune tolerance is maintained and how it may breakdown. Conclusion: The breakdown of immune homeostasis following the development of gut inflammation, caused for example by gut dysbiosis, and the consequent increased intestinal permeability, is increasingly considered to be the ultimate source of the systemic immune activation and T helper 17/T regulatory cell imbalances, and maybe neurological disturbances, seen in autoimmune diseases such as Type 1 diabetes and inflammatory bowel disease. Increased intestinal permeability and translocation of commensal antigens into the systemic circulation is also a likely cause of the severe fatigue and an almost bewildering range of neurocognitive, neuroimaging and overall symptom presentations seen in patients with a diagnosis of Chronic Fatigue Syndrome.
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