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Wednesday, August 14, 2013

Is the human gut microbiota the critical mediator of health?

In a review this month, Greer and co-authors present interesting information on just how much our health depends on the well-being and communal balance of the microscopic symbionts in our gastrointestinal tract [Journal of Allergy and Clinical Immunology 2013; 132(2): 253-262].  They begin their review noting that, until fairly recently, immunity, metabolic functions and gut physiology had been studied as separate biological systems.  In light of growing evidence that the delineation between these is arbitrary, the authors point out that systems biology has developed new methods for investigating the interactions between the intestinal microbiota and immune and metabolic outcomes.

Greer et al covers two broad categories, small intestine enteropathies and obesity with metabolic syndrome.  They describe current animal models used to study immunodeficiency enteropathies, celiac disease, inflammatory bowel disease, obesity and lipid metabolism dysregulation.

The authors discuss notable findings from mouse models that have been employed to study enteropathies.  For example, B lymphocyte deficient mice are known have fat absorption issues, which correlate to IgA deficiency.  B cell secreted IgA is required for maintaining a proper balance between immunity, fat metabolism and gut microbes.  They note that B cell deficient mice have intestinal gene expression profiles that are very similar to those seen in HIV/CVID patients.

They note that gut microbiota contribute to dyslipidemia and insulin resistance in obese mice and induce intestinal inflammation in response to increased fat intake.  Greer et al discuss also the physical changes in the ileum that cause increased uptake of fats in the diet-induced obese mice.  Interesting, they comment that TLR5 knock-out mice have increased weight gain, pointing to innate immune interactions in fat metabolism.

Greer et al discuss evidence on short chain fatty acid balance and metabolism as critical to maintenance of a “core” microbiota.  Transplantation of microbes from diet-induced obese mice to control mice results in obesity in the control mice without increase in food intake.  The authors suggest that this points to persisting changes in gut microbiota that may be causally related to obesity and altered fat metabolism.  Concluding, Greer et al suggest that the gut microbiota is a cardinal mediator between the immune system and gastrointestinal epithelium. 

In answer to the question, "In your opinion, does manipulation of the gut microbiota present a therapeutic intervention for obesity and/or lipid metabolism disorders?", the authors responded, "Yes, we believe that manipulation of gut microbiota presents great potential for therapeutic interventions in a range of diseases, including obesity and metabolic syndrome, but we need first to understand which taxa or which microbial genes might be most beneficial and in each case."

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