The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome
André F. Carvalho,
Javier R. Caso,
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
Keywords: Microbiota, microbiome, leaky gut, intestinal permeability, autoimmunity, inflammation.
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