Obesity and its associated disease: a role for microbiota? (original) (raw)

Gut microbiota in obesity and metabolic disorders

Proceedings of the Nutrition Society, 2010

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

Impact of the gut microbiota on inflammation, obesity, and metabolic disease

The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.

Microbiota and Obesity: Where Are We Now?

Biology, 2020

Emerging new data reported in the international scientific literature show that specific alterations in the human gut microbiota are characteristic in obesity and obesity-related metabolic diseases. Obesity is conditioned by a multitude of factors, and the microbiota is certainly an important player. The analysis of the data obtained from experimental studies allow us to hypothesize that changes in the composition of the microbiota may be the cause, and not simply the consequence, of alterations in human metabolism. Clinical trials on wide samples that investigate the role of diet-induced modulation of the gut microbiota on the host metabolism are needed to understand the interactions at the molecular level for the observed correlations between metabolism and microbiota changes.

Gut Microbiota: From Microorganisms to Metabolic Organ Influencing Obesity

Obesity (Silver Spring, Md.), 2018

This review summarizes the current understanding of the relationship between gut microbiota and the host as it pertains to the regulation of energy balance and obesity. The paper begins with a brief description of the gut microbiota environment, distribution, and its unique symbiotic relationship with the host. The way that enviromental factors influence microbiota composition and subsequent impact on the host are then described. Next, the mechanisms linking gut dysbiosis with obesity are discussed, and finally current challenges and limitations in understanding the role of gut microbiota in control of obesity are presented. Gut microbiota has been implicated in regulation of fat storage, as well as gut dysbiosis, thus contributing to the development of obesity, insulin resistance, hyperglycemia and hyperlipidemia. However, the underlying mechanisms of these processes are far from being clear and will require complex preclinical and clinical interdisciplinary studies of bacteria and...

The Role of the Gut Microbiota in Energy Metabolism and Metabolic Disease

Current Pharmaceutical Design

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.

Translational research into gut microbiota: new horizons in obesity treatment

Arquivos Brasileiros de Endocrinologia & Metabologia, 2009

Obesity is a pandemic which has been rapidly developing for three decades. When a population is submitted to the same nutritional stress, some individuals are less susceptible to dietinduced weight gain and hyperglycemia. This observation suggests that other mechanisms are involved which are not directly related to the human genome. The human gut contains an immense number of microorganisms, collectively known as the microbiota. Evidence that gut microbiota composition can differ between obese and lean humans has led to the speculation that gut microbiota can participate in the pathophysiology of obesity. Different mechanisms have been proposed to explain the link between gut flora and obesity. The first mechanism consists in the role of the gut microbiota to increase energy extraction from indigestible dietary polysaccharides. The second, consists in the role of gut flora to modulate plasma lipopolysaccharide levels which triggers chronic low-grade inflammation leading to obesity and diabetes. A third mechanism proposes that gut microbiota may induce regulation of host genes that modulate how energy is expended and stored. However, further studies are needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Arq Bras Endocrinol Metab. 2009;53(2):139-144.

Evidence on the role of gut microbes in obesity Revisión

Obesity results from a positive energy im- balance and it is associated with a chronic low-grade inflammation. The microbiota that populates the gut is considered a novel factor that, together with lifestyle, may be involved in obesity. On the one hand, the gut microbiota is globally involved in energy metabolism by im- proving the host's ability to extract and store energy from the diet. On the other, the com- mensal microbiota regulates immune functions, protecting the host from infections and chronic inflammation. Saturated lipids and Gram- negative bacteria trigger similar proinflamma- tory responses through their recognition by the same receptors of innate immune cells and adipocytes, associated with obesity and insulin resistance. Metabolic endotoxaemia is also a possible inflammatory factor causative of insu- lin resistance development and weight gain in animal models. In contrast, the administration of certain prebiotics may reverse this process and restore the gut balan...

Obesity and microbiota: an example of an intricate relationship

Genes & Nutrition

It is widely accepted that metabolic disorders, such as obesity, are closely linked to lifestyle and diet. Recently, the central role played by the intestinal microbiota in human metabolism and in progression of metabolic disorders has become evident. In this context, animal studies and human trials have demonstrated that alterations of the intestinal microbiota towards enhanced energy harvest is a characteristic of the obese phenotype. Many publications, involving both animal studies and clinical trials, have reported on the successful exploitation of probiotics and prebiotics to treat obesity. However, the molecular mechanisms underlying these observed anti-obesity effects of probiotics and prebiotic therapies are still obscure. The aim of this mini-review is to discuss the intricate relationship of various factors, including diet, gut microbiota, and host genetics, that are believed to impact on the development of obesity, and to understand how modulation of the gut microbiota with dietary intervention may alleviate obesity-associated symptoms.

Gut microbiota and the development of obesity

Resumen Introducción: Los avances en herramientas para la investigación molecular han permitido una mayor com-prensión de cómo los microbios pueden influir en la fisio-logía del huésped. Un campo de investigación muy intere-sante que se ha llamado la atención recientemente es el posible papel de la microbiota intestinal en el desarrollo de la obesidad y de los trastornos metabólicos. Objetivos: El objetivo de esta revisión es discutir los mecanismos que explican la influencia de la microbiota intestinal en el metabolismo del huésped. Resultados y discusión: La microbiota intestinal es importante para la fisiología normal del huésped. Sin embargo, las diferencias en su composición pueden tener efectos diferentes sobre el metabolismo del huésped. Se ha demostrado que las personas obesas y delgadas tienen un perfil de composición diferente de la microbiota. Estas diferencias en la composición de la microbiota pueden contribuir a un desequilibrio de peso y alteración del metabolismo. Las evidencias de los modelos animales sugieren que es posible que la microbiota de los sujetos obesos tienen una mayor capacidad para captar energía de la dieta proporcionando sustratos que pueden activar las vías lipogénicas. Además, los microorganismos tam-bién pueden influir en la actividad de la lipoproteína lipasa lo que interfiere con la acumulación de triglicéri-dos en el tejido adiposo. La interacción de la microbiota intestinal con el sistema endocannabinoide proporciona una ruta a través del cual puede alterar la permeabilidad intestinal. Aumento de la permeabilidad intestinal per-mite la entrada de la circulación de endotoxinas, que están relacionados con la inducción de la inflamación y la resistencia a la insulina en los ratones. El impacto de los mecanismos propuestos para los seres humanos todavía necesita uma mayor investigación. Sin embargo, el hecho de que la microbiota intestinal puede ser modulada por componentes de la dieta refuerza la importancia de estu-diar cómo los ácidos grasos, hidratos de carbono, micro-nutrientes, prebióticos y probióticos pueden influir en la composición de la microbiota intestinal y el desarrollo de la obesidad. La microbiota intestinal parece ser un obje-tivo importante y prometedor en la prevención y el trata-miento de la obesidad y trastornos metabólicos relaciona-dos en la investigación futura y la práctica clínica. Abstract Introduction: Advances in tools for molecular investigations have allowed deeper understanding of how microbes can influence host physiology. A very interesting field of research that has gained attention recently is the possible role of gut microbiota in the development of obesity and metabolic disorders. Objective: The aim of this review is to discuss mechanisms that explain the influence of gut microbiota on host metabolism. Results and discussion: The gut microbiota is important for normal physiology of the host. However, differences in their composition may have different impacts on host metabolism. It has been shown that obese and lean subjects present different microbiota composition profile. These differences in microbiota composition may contribute to weight imbalance and impaired metabolism. The evidences from animal models suggest that it is possible that the microbiota of obese subjects has higher capacity to harvest energy from the diet providing substrates that can activate lipogenic pathways. In addition, microorganisms can also influence the activity of lipoprotein lipase interfering in the accumulation of triglycerides in the adipose tissue. The interaction of gut microbiota with the endocannabinoid system provides a route through which intestinal perme-ability can be altered. Increased intestinal permeability allows the entrance of endotoxins to the circulation, which are related to the induction of inflammation and insulin resistance in mice. The impact of the proposed mechanisms for humans still needs further investigations. However, the fact that gut microbiota can be modulated through dietary components highlights the importance to study how fatty acids, carbohydrates, micronutrients, prebiotics, and probiotics can influence gut microbiota composition and the management of obesity. Gut microbiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances in future studies and in clinical practice.

Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota

Current Opinion in Pharmacology, 2009

Obesity and associated metabolic disorders are worldwide epidemic. The literature provides new evidence that gut microbiota dysbiosis (at the phyla, genus, or species level) affects host metabolism and energy storage. Here we discuss new findings that may explain how gut microbiota can be involved in the development or in the control of obesity and associated low-grade inflammation. New powerful molecular biology methods and the use of gnotobiotic animal allowed to analyze the molecular link between gut bacteria and the host. Moreover, even if more studies are needed to unravel how changing gut microbiota impacts on the development of obesity and related metabolic alterations, probiotic and prebiotic approach appear as potential interesting treatments to reverse host metabolic alterations linked to gut microbiota dysbiosis. Xaus J: Beneficial effects of probiotic bacteria isolated from breast milk. Br J Nutr 2007, 98(Suppl 1):S96-100.