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Diseases 2018, 6(2), 23;

The Brain–Intestinal Mucosa–Appendix– Microbiome–Brain Loop

Sydney Medical School, The University of Sydney, Sydney 2006, Australia
Medlab Clinical Ltd., Sydney 2015, Australia
Author to whom correspondence should be addressed.
Received: 5 February 2018 / Revised: 28 February 2018 / Accepted: 29 March 2018 / Published: 1 April 2018
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3–4 years of age. Furthermore, it is understood that the microbiome promotes cues that instruct the neonate’s mucosal tissues and skin in the language of molecular and cellular biology. Post birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged co-establishing the intestinal microbiome with a developing immune system. Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via shifts in the intestinal microbiome phyla. A plausible appreciation is that dysregulated pro-inflammatory signals from intestinal resident macrophages could breach the loop by providing adverse mood signals via vagus nerve afferents to the brain. In this commentary, we further suggest that the intestinal resident macrophages act as an upstream traffic controller of translocated microbes and metabolites in order to maintain local neuro-endocrine-immunological equilibrium. When macrophages are overwhelmed through intestinal microbiome and intestinal epithelial cell dysbiosis, pro-inflammatory signals are sustained, which may then lead to mood disorders. The administration of probiotics as an adjunctive medicine co-administered with antidepressant medications in improving depressed mood may have biological and clinical standing. View Full-Text
Keywords: brain-intestinal-brain axis; intestinal epithelia; macrophages; vagus nerve; microbiome; dysbiosis; vermiform appendix; probiotics brain-intestinal-brain axis; intestinal epithelia; macrophages; vagus nerve; microbiome; dysbiosis; vermiform appendix; probiotics

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Vitetta, L.; Vitetta, G.; Hall, S. The Brain–Intestinal Mucosa–Appendix– Microbiome–Brain Loop. Diseases 2018, 6, 23.

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