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Gut-adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?
Rosendo-Silva, D, Matafome, P
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(2):e13130
Abstract
The gut is one of the main endocrine organs in our body, producing hormones acknowledged to play determinant roles in controlling appetite, energy balance and glucose homeostasis. One of the targets of such hormones is the adipose tissue, a major energetic reservoir, which governs overall metabolism through the secretion of adipokines. Disturbances either in nutrient and metabolic sensing and consequent miscommunication between these organs constitute a key driver to the metabolic complications clustered in metabolic syndrome. Thus, it is essential to understand how the disruption of this crosstalk might trigger adipose tissue dysfunction, a strong characteristic of obesity and insulin resistance. The beneficial effects of metabolic surgery in the amelioration of glucose homeostasis and body weight reduction allowed to understand the potential of gut signals modulation as a treatment for metabolic syndrome-related obesity and type 2 diabetes. In this review, we cover the effects of gut hormones in the modulation of adipose tissue metabolic and endocrine functions, as well as their impact in tissue plasticity. Furthermore, we discuss how the modulation of gut secretome, either through surgical procedures or pharmacological approaches, might improve adipose tissue function in obesity and metabolic syndrome.
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2.
Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome.
Moossavi, S, Bishehsari, F
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(3):407-419
Abstract
The rapid decrease in infectious diseases globally has coincided with an increase in the prevalence of obesity and other components of metabolic syndrome. Insulin resistance is a common feature of metabolic syndrome and can be influenced by genetic and non-genetic/environmental factors. The emergence of metabolic syndrome epidemics over only a few decades suggests a more prominent role of the latter. Changes in our environment and lifestyle have indeed paralleled the rise in metabolic syndrome. Gastrointestinal tract microbiota, the composition of which plays a significant role in host physiology, including metabolism and energy homeostasis, are distinctly different within the context of metabolic syndrome. Among humans, recent lifestyle-related changes could be linked to changes in diversity and composition of 'ancient' microbiota. Given the co-adaptation and co-evolution of microbiota with the immune system over a long period of time, it is plausible that such lifestyle-related microbiota changes could trigger aberrant immune responses, thereby predisposing an individual to a variety of diseases. Here, we review current evidence supporting a role for gut microbiota in the ongoing rise of metabolic syndrome. We conclude that population-level shifts in microbiota can play a mediatory role between lifestyle factors and pathogenesis of insulin resistance and metabolic syndrome.
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[Microbiome & NASH - partners in crime driving progression of fatty liver disease].
Wree, A, Geisler, LJ, Tacke, F
Zeitschrift fur Gastroenterologie. 2019;(7):871-882
Abstract
Along with the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and poses a major challenge for gastroenterologists. Many studies have demonstrated that the microbiome is closely associated with the progression of nutrition-related diseases, especially of fatty liver disease. Changes in the quantity and quality of the intestinal flora, commonly referred to as dysbiosis, result in altered food metabolism, increased permeability of the intestinal barrier ("leaky gut") and consecutive inflammatory processes in the liver. This favors both the progression of obesity and metabolic disorders as well as NAFLD towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Important molecular mechanisms include microbial metabolites, microbial and endogenous signaling substances (so-called PAMPs/DAMPs) as well as bile acids. Essential cellular mechanisms include immune cells in the gut and liver, especially macrophages and Kupffer cells, as well as intestinal epithelial cells and hepatocytes as central regulators of metabolism. In this review article, we briefly summarize the relevant species of the human microbiome, describe the microbial analytics, explain the most important molecular relationships between microbiome and NAFLD/NASH, and finally the opportunities and challenges of microbiome-modulating therapy for the treatment of fatty liver disease.
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[The human gut microbiota: Interactions with the host and dysfunctions].
Lepage, P
Revue des maladies respiratoires. 2017;(10):1085-1090
Abstract
The human intestinal microbiota is composed of approximately 100,000 billion microorganisms with the average total number of different commensal bacterial species estimated at over 500 per individual. The human intestinal microbiota can be considered as an organ within another, which co-evolved with its host to achieve a symbiotic relationship leading to physiological homeostasis. The host provides an environment enriched in nutrients and the microbiota provides essential functions. Dysbiosis of the intestinal microbiota (changes in bacterial composition) has been associated with local dysfunctions of the gastrointestinal tract, such as inflammatory bowel disease or irritable bowel syndrome but also with obesity and metabolic diseases. However, a better understanding of the human intestinal ecosystem is still needed to understand the exact role of the microbiota in health and disease. Most intestinal bacteria are anaerobic and therefore, for the large majority, impossible to culture at present. Consequently, their function cannot be inferred from data on their composition. Today, with the help of a metagenomic approach, the bacterial genomic content of an ecosystem and the associated functions can be directly accessed from the environment without culture.
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The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: study protocol for a randomized controlled trial.
Kassaian, N, Aminorroaya, A, Feizi, A, Jafari, P, Amini, M
Trials. 2017;(1):148
Abstract
BACKGROUND The incidence of type 2 diabetes, cardiovascular diseases, and obesity has been rising dramatically; however, their pathogenesis is particularly intriguing. Recently, dysbiosis of the intestinal microbiota has emerged as a new candidate that may be linked to metabolic diseases. We hypothesize that selective modulation of the intestinal microbiota by probiotic or synbiotic supplementation may improve metabolic dysfunction and prevent diabetes in prediabetics. In this study, a synthesis and study of synbiotics will be carried out for the first time in Iran. METHODS/DESIGN In a randomized triple-blind controlled clinical trial, 120 adults with impaired glucose tolerance based on the inclusion criteria will be selected by a simple random sampling method and will be randomly allocated to 6 months of 6 g/d probiotic, synbiotic or placebo. The fecal abundance of bacteria, blood pressure, height, weight, and waist and hip circumferences will be measured at baseline and following treatment. Also, plasma lipid profiles, HbA1C, fasting plasma glucose, and insulin levels, will be measured and insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) will be calculated at baseline and will be repeated at months 3, 6, 12, and 18. The data will be compared within and between groups using statistical methods. DISCUSSION The results of this trial could contribute to the evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in prevention and management of metabolic syndrome in prediabetes. TRIAL REGISTRATION Iranian Registry of Clinical Trials: IRCT201511032321N2 . Registered on 27 February 2016.
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Schizophrenia and the gut-brain axis.
Nemani, K, Hosseini Ghomi, R, McCormick, B, Fan, X
Progress in neuro-psychopharmacology & biological psychiatry. 2015;:155-60
Abstract
Several risk factors for the development of schizophrenia can be linked through a common pathway in the intestinal tract. It is now increasingly recognized that bidirectional communication exists between the brain and the gut that uses neural, hormonal, and immunological routes. An increased incidence of gastrointestinal (GI) barrier dysfunction, food antigen sensitivity, inflammation, and the metabolic syndrome is seen in schizophrenia. These findings may be influenced by the composition of the gut microbiota. A significant subgroup of patients may benefit from the initiation of a gluten and casein-free diet. Antimicrobials and probiotics have therapeutic potential for reducing the metabolic dysfunction and immune dysregulation seen in patients with schizophrenia.
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Potential role of the intestinal microbiota in programming health and disease.
Goulet, O
Nutrition reviews. 2015;:32-40
Abstract
The composition of the microbiota varies according to prenatal events, delivery methods, infant feeding, infant care environment, and antibiotic use. Postnatal gut function and immune development are largely influenced by the intestinal microbiota. Emerging evidence has shown that early microbiota colonization may influence the occurrence of later diseases (microbial programming). The vast majority of microbial species (commensals) give rise to symbiotic host-bacterial interactions that are fundamental for human health. However, changes in the composition of the gut microbiota (dysbiosis) may be associated with several clinical conditions, including obesity and metabolic diseases, autoimmune diseases and allergy, acute and chronic intestinal inflammation, irritable bowel syndrome (IBS), allergic gastroenteritis (e.g., eosinophilic gastroenteritis and allergic IBS), and necrotizing enterocolitis. Based on recent advances, modulation of gut microbiota with probiotics, prebiotics, or fermented dairy products has been suggested as a treatment of, or prevention for, different disorders such as IBS, infectious diarrhea, allergic disease, and necrotizing enterocolitis.
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8.
[The gut microbiota in sickness and health].
Lankelma, JM, Nieuwdorp, M, de Vos, WM, Wiersinga, WJ
Nederlands tijdschrift voor geneeskunde. 2014;:A5901
Abstract
The human gut microbiota, formerly known as 'gut flora', may be regarded as an external organ with many physiological functions in metabolism, development of the immune system and defense against pathogens. The adult gut microbiota consist of 1013-1014 micro-organisms. The aggregate genome of these, known as the microbiome, is 100 times larger than the human genome. The gut microbiotica may be involved in the pathogenesis of a range of syndromes, such as inflammatory bowel disease, obesity, diabetes mellitus and atopic disorders. It should be noted that until now most of the studies conducted have been association studies, without proof of causality. This increasing insight has led to identification of new therapeutic strategies, which are currently being investigated in clinical studies. Although the implications of this knowledge for individual patients have yet to become clear, various interventions are conceivable, such as supplementation of nutritional elements, prebiotics or probiotics and feces transplantation.
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The microbiome in inflammatory bowel disease and its modulation as a therapeutic manoeuvre.
Hart, AL, Hendy, P
The Proceedings of the Nutrition Society. 2014;(4):452-6
Abstract
Inflammatory bowel disease (IBD) is increasing in incidence in both the developed and the developing world. Genetic, immunological and environmental factors are known to be involved. Genome-wide studies have examined the contribution played by host genetics in the development of IBD and have estimated that genetic factors are responsible for about 25 % of the disease risk. Having an IBD-associated genotype does not always lead to development of the disease phenotype, and hence it seems likely that environmental factors are key to triggering development of the disease in genetically susceptible individuals. The gut microbiota contains more cells than its human host, and mounting evidence attests to the importance of the microbiota in the development of several diseases, including IBD, metabolic syndrome and CVD. The present paper reviews the interplay between the microbiota and the mucosal immune system in health and in IBD; and discusses the evidence base for the use of therapeutic modulation of the microbiota to prevent and treat IBD.
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Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet.
Roager, HM, Licht, TR, Poulsen, SK, Larsen, TM, Bahl, MI
Applied and environmental microbiology. 2014;(3):1142-9
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Abstract
It has been suggested that the human gut microbiota can be divided into enterotypes based on the abundance of specific bacterial groups; however, the biological significance and stability of these enterotypes remain unresolved. Here, we demonstrated that subjects (n = 62) 18 to 65 years old with central obesity and components of metabolic syndrome could be grouped into two discrete groups simply by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Furthermore, we showed that these groups remained stable during a 6-month, controlled dietary intervention, where the effect of consuming a diet in accord with the new Nordic diet (NND) recommendations as opposed to consuming the average Danish diet (ADD) on the gut microbiota was investigated. In this study, subjects (with and without stratification according to P/B ratio) did not reveal significant changes in 35 selected bacterial taxa quantified by quantitative PCR (ADD compared to NND) resulting from the dietary interventions. However, we found higher total plasma cholesterol within the high-P/B group than in the low-P/B group after the intervention. We propose that stratification of humans based simply on their P/B ratio could allow better assessment of possible effects of interventions on the gut microbiota and physiological biomarkers.