The Crosstalk between Gut Microbiota, Intestinal Immunological Niche and Visceral Adipose Tissue as a New Model for the Pathogenesis of Metabolic and Inflammatory Diseases: The Paradigm of Type 2 Diabetes Mellitus

Abstract

Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa, and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides produced in gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides, it is involved in lipid and glucose metabolism and in some immune reactions through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a proinflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is clearly associated with specific patterns of GM alterations, with an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to a new, interesting therapeutic approach.

Liver microbiota in healthy rats: the hidden inhabitants of hepatocytes

“…The 16S rRNA gene signature was also demonstrated in the blood of healthy humans (primarily leukocyte and platelet fractions) [20] or patients [21,22] as well as in the circulation of animals [23][24][25]. These key factors illustrate the crosstalk line between the gut microbiota, circulation, and tissues [26], that is, the gut microbiota enter into the circulation through leakage and locate into tissues and change into tissue microbiota/tumor type-speci c intracellular bacteria. They then cause disease, although the mechanism of tissue microbiota development remains a hypothesis [27].…”

Liver microbiome in healthy rats: the hidden inhabitants of hepatocytes

“…The 16S rRNA gene signature was also demonstrated in the blood of healthy humans (primarily leukocyte and platelet fractions) [19] or patients [20,21] as well as in the circulation of animals [22][23][24]. These key factors illustrate the crosstalk line between the gut microbiota, circulation, and tissues [25]; that is, the gut microbiota enter into the circulation through leakage and locate into tissues and change into tissue microbiota/tumor type-speci c intracellular bacteria. They then cause disease, although the mechanism of tissue microbiota development remains a hypothesis [26].…”

The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies

“…Gut microbiota (GM) play a pivotal role in balancing not only intestinal immunological response at gut surface but also the individual inflammatory status in the course of pathologies involving organs different from the gut or in systemic diseases [ 5 ]. On the other hand, when a pathologic or physiologic condition induces a variation in GM composition or an abnormally permeable gut mucosa (“leaky gut”), GM can exert an influence on pre-existing diseases or increase the risk of pathological conditions [ 5 ].…”

“…Overall, many conditions in which the immune system is dysregulated have been linked to the development of HF. These pathologies range from lupus erythematosus to diabetes and obesity [ 3 , 4 , 5 ]. Part of the changes in the function of the immune system may also not be directly determined by the inflammatory condition itself but through modifications of the gut microbiota, which is a key factor in the regulation and modulation of the immune system [ 6 , 7 ].…”