Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between ...healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY...), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.
At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act ...as an environmental factor that affects the host's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ-free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut's barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity-related disorders.
Alterations in the composition of gut microbiota--known as dysbiosis--has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting ...the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice.
Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters.
Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention.
Gut dysbiosis was recently associated with the occurrence of type 2 diabetes (T2D). In addition to this finding, an increasing number of studies performed upon the last 5 years have also shown that ...metformin treatment leads to changes in gut bacterial composition in diabetic patients. This review focuses on the articles describing the effects of metformin on gut homeostasis (including the gut microbiota) and proposes potential mechanisms involved in those effects.
Several human and animal studies emphasized that metformin alters the gut microbiota composition by enhancing the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and by decreasing the levels of some other ones like Intestinibacter. In-vitro studies also demonstrated a direct action of metformin on the growth of A. muciniphila and Bifidobacterium adolescentis. Moreover, in the intestines, metformin does not only improve the glucose uptake, but it also promotes the short-chain fatty acid (SCFA) production, protects the intestinal barrier and regulates the secretion of gut peptides SUMMARY: It is now clear that gut microbiota participates to the glucose-lowering effects of metformin in the context of diabetes. Further work is now needed to determine the exact mechanisms of action of the drug and to understand by which processes metformin is able to enhance the growth of some bacteria exhibiting beneficial effects for the host.
Muscle wasting is characterized by a loss of muscle mass and strength, and occurs in several pathological conditions such as cancer, chronic heart failure, chronic infection and malnutrition. Muscle ...wasting can be caused by inflammation and inappropriate nutritional status. Interestingly, gut microbiota has recently been proposed as an environmental factor involved, among others, in energy sparing from the diet, and in the regulation of host immunity and metabolism. This review presents evidence supporting the existence of a gut microbiota-muscle axis and discusses the potential role and therapeutic interest of gut microbiota in muscle wasting, specifically in the context of cancer and malnutrition. This review also proposes possible molecular mechanisms underlying the gut microbiota-muscle axis.
This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of ...synbiotics. The panel updated the definition of a synbiotic to "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host". The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
Towards a more comprehensive concept for prebiotics Bindels, Laure B; Delzenne, Nathalie M; Cani, Patrice D ...
Nature reviews. Gastroenterology & hepatology,
05/2015, Letnik:
12, Številka:
5
Journal Article
Recenzirano
The essential role of the gut microbiota for health has generated tremendous interest in modulating its composition and metabolic function. One of these strategies is prebiotics, which typically ...refer to selectively fermented nondigestible food ingredients or substances that specifically support the growth and/or activity of health-promoting bacteria that colonize the gastrointestinal tract. In this Perspective, we argue that advances in our understanding of diet-microbiome-host interactions challenge important aspects of the current concept of prebiotics, and especially the requirement for effects to be 'selective' or 'specific'. We propose to revise this concept in an effort to shift the focus towards ecological and functional features of the microbiota more likely to be relevant for host physiology. This revision would provide a more rational basis for the identification of prebiotic compounds, and a framework by which the therapeutic potential of modulating the gut microbiota could be more fully materialized.
This review examines mechanisms by which the bacteria present in the gut interact with nutrients and host biology to affect the risk of obesity and associated disorders, including diabetes, ...inflammation, and liver diseases. The bacterial metabolism of nutrients in the gut is able to drive the release of bioactive compounds (including short-chain fatty acids or lipid metabolites), which interact with host cellular targets to control energy metabolism and immunity. Animal and human data demonstrate that phylogenic changes occur in the microbiota composition in obese versus lean individuals; they suggest that the count of specific bacteria is inversely related to fat mass development, diabetes, and/or the low levels of inflammation associated with obesity. The prebiotic and probiotic approaches are presented as interesting research tools to counteract the drop in target bacteria and thereby to estimate their relevance in the improvement of host metabolism.
Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect ...gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila , which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
Each human intestine harbours not only hundreds of trillions of bacteria but also bacteriophage particles, viruses, fungi and archaea, which constitute a complex and dynamic ecosystem referred to as ...the gut microbiota. An increasing number of data obtained during the last 10 years have indicated changes in gut bacterial composition or function in type 2 diabetic patients. Analysis of this ‘dysbiosis’ enables the detection of alterations in specific bacteria, clusters of bacteria or bacterial functions associated with the occurrence or evolution of type 2 diabetes; these bacteria are predominantly involved in the control of inflammation and energy homeostasis. Our review focuses on two key questions: does gut dysbiosis truly play a role in the occurrence of type 2 diabetes, and will recent discoveries linking the gut microbiota to host health be helpful for the development of novel therapeutic approaches for type 2 diabetes? Here we review how pharmacological, surgical and nutritional interventions for type 2 diabetic patients may impact the gut microbiota. Experimental studies in animals are identifying which bacterial metabolites and components act on host immune homeostasis and glucose metabolism, primarily by targeting intestinal cells involved in endocrine and gut barrier functions. We discuss novel approaches (e.g. probiotics, prebiotics and faecal transfer) and the need for research and adequate intervention studies to evaluate the feasibility and relevance of these new therapies for the management of type 2 diabetes.
PDF
