The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype

The aim of this study was to investigate the effect of high-far-high-energy diet on cloned and non-cloned domestic pigs of both lean and obese phenotype and to evaluate if the lean cloned pigs had a lower inter-individual variation as compared with non-cloned pigs. The microbiota of colon and terminal ileum was investigated in cloned and non-cloned pigs that received a high-far-high-energy diet with either restricted or ad libitum access to feed, resulting in lean and obese phenotypes, respectively. The fecal microbiota of lean pigs was investigated by terminal restriction fragment length polymorphism (T-RFLP). The intestinal microbiota of lean and obese cloned and non-cloned pigs was analyzed by quantitative real time PCR and a novel high-throughput qPCR platform (Fluidigm). Principal component analysis (PCA) of the T-RFLP profiles revealed that lean cloned and non-cloned pigs had a different overall composition of their gut microbiota. The colon of lean cloned pigs contained relatively more bacteria belonging to the phylum Firmicutes and less from the phylum Bacteroidetes than obese cloned pigs as estimated by qPCR. Fluidigm qPCR results revealed differences in specific bacterial groups in the gut microbiota of both lean and obese pigs. Our results suggest that high-far-high-energy diet is associated with changes in the gut microbiota even in the absence of obesity. Overall, the cloned pigs had a different gut microbiota from that of non-cloned pigs. To our knowledge this is the first study to investigate the gut microbiota of cloned domestic pigs of lean and obese phenotype.     

Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome

Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.     

Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome

Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.     

Nutrition,the gut microbiome and the metabolic syndrome

Metabolic syndrome is a lifestyle disease, determined by the interplay of genetic and environmental factors. Obesity is a significant risk factor for development of the metabolic syndrome, and the prevalence of obesity is increasing due to changes in lifestyle and diet. Recently, the gut microbiota has emerged as an important contributor to the development of obesity and metabolic disorders, through its interactions with environmental (e.g. diet) and genetic factors. Human and animal studies have shown that alterations in intestinal microbiota composition and shifts in the gut microbiome towards increased energy harvest are associated with an obese phenotype. However, the underlying mechanisms by which gut microbiota affects host metabolism still need to be defined.In this review we discuss the complexity surrounding the interactions between diet and the gut microbiota, and their connection to obesity. Furthermore, we review the literature on the effects of probiotics and prebiotics on the gut microbiota and host metabolism, focussing primarily on their anti-obesity potential.     

Obesity alters gut microbial ecology

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals. The sequences reported in this paper have been deposited in the GenBank database [accession nos. DQ 014552--DQ 015671 (mothers) and AY 989911--AY 993908 (offspring)].     

Do nutrient–gut–microbiota interactions play a role in human obesity,insulin resistance and type 2 diabetes?

The current obesity and type 2 diabetes pandemics have causes beyond changes in eating and exercise habits against a susceptible genetic background. Gut bacteria seem to additionally contribute to the differences in body weight, fat distribution, insulin sensitivity and glucose‐ and lipid‐metabolism. Data, mostly derived from preclinical studies, suggest that gut microbiota play an important role in conditions such as obesity, diabetes, metabolic syndrome and non‐alcoholic fatty liver disease. Regulation of energy uptake from the gut, by digesting otherwise indigestible common polysaccharides in our diet, production or activation of signalling molecules involved in host metabolism, modification of gut permeability, the release of gut hormones and inflammation, are among the mechanisms by which gut microbiota may influence the host cardiometabolic phenotype. Recent evidence suggests that quantitative and qualitative differences in gut microbiota exist between lean and obese, and between diabetic and non‐diabetic individuals. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may favourably affect host metabolism. Large‐scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high‐risk populations, are eagerly awaited.     

The environment within: how gut microbiota may influence metabolism and body composition

Obesity, diabetes and consequently atherosclerotic vascular disease have become major health and public health issues worldwide. The increasing and staggering prevalence of obesity might not only be explained by nutritional habits or the reduction of energy expenditure through decreased physical activity. In addition, recent studies have focused on intestinal microbiota as environmental factors that increase energy yield from diet, regulate peripheral metabolism and thereby increase body weight. Obesity is associated with substantial changes in composition and metabolic function of gut microbiota, but the pathophysiological processes driving this bidirectional relationship have not been fully elucidated. This review discusses the relationships between the following: composition of gut microbiota, energy extracted from diet, synthesis of gut hormones involved in energy homeostasis, production of butyrate and the regulation of fat storage.     

Glucose metabolism: Focus on gut microbiota,the endocannabinoid system and beyond

The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D.     

The role of gut microbiota in human obesity: Recent findings and future perspectives

AimsIn recent years, gut microbiota have gained a growing interest as an environmental factor that may affect the predisposition toward adiposity. In this review, we describe and discuss the research that has focused on the involvement of gut microbiota in human obesity. We also summarize the current knowledge concerning the health effects of the composition of gut microbiota, acquired using the most recent methodological approaches, and the potential influence of gut microbiota on adiposity, as revealed by animal studies.Data synthesisOriginal research studies that were published in English or French until December 2011 were selected through a computer-assisted literature search. The studies conducted to date show that there are differences in the gut microbiota between obese and normal-weight experimental animals. There is also evidence that a high-fat diet may induce changes in gut microbiota in animal models regardless of the presence of obesity. In humans, obesity has been associated with reduced bacterial diversity and an altered representation of bacterial species, but the identified differences are not homogeneous among the studies.ConclusionsThe question remains as to whether changes in the intestinal microbial community are one of the environmental causes of overweight and obesity or if they are a consequence of obesity, specifically of the unbalanced diet that often accompanies the development of excess weight gain. In the future, larger studies on the potential role of intestinal microbiota in human obesity should be conducted at the species level using standardized analytical techniques and taking all of the possible confounding variables into account.     

Gut Microbiota as a Modulator of Cardiometabolic Risk: Mechanisms and Therapeutic Implications

Obesity-related disorders result from the combination of genetic susceptibility and environmental factors, including gut microbiota. Evidence from animal models provides insight into several mechanisms underlying the interaction between microbiome and host metabolic and inflammatory responses, such as increased energy harvest from the diet, regulation of intestinal transit rate and mucosal barrier function, modulation of fatty acid metabolism, and lipopolysaccharide-induced activation of Toll-like receptor-4 inflammatory pathway. In humans, gut microbiota alterations could link high energy intake and obesity-related cardiometabolic disorders; the composition of intestinal microflora of obese patients differs from that of lean subjects and microbiota manipulation through prebiotic/probiotics or microbial transplantation can affect post-prandial endotoxinemia levels and glucose metabolism. We discuss mechanisms connecting gut microbiota to obesity-related diseases and potential therapeutic applications.     

饮食干预对非酒精性脂肪性肝病肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)的发生与遗传和环境密切相关,肠道菌群在其发生和发展中发挥了重要作用,调节肠道菌群已成为干预NAFLD的重要靶点之一.无论是饮食总量还是结构都会对肠道菌群产生直接且长期的影响.通过低脂饮食、增加饮食中不饱和脂肪酸或者增加难以吸收的多糖等方式调整饮食结构,可以有效调节肠道菌群并治疗NAFLD,但高蛋白饮食的作用还存在争议.     

The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus

Obesity and type 2 diabetes mellitus (T2DM) are attributed to a combination of genetic susceptibility and lifestyle factors. Their increasing prevalence necessitates further studies on modifiable causative factors and novel treatment options. The gut microbiota has emerged as an important contributor to the obesity--and T2DM--epidemic proposed to act by increasing energy harvest from the diet. Although obesity is associated with substantial changes in the composition and metabolic function of the gut microbiota, the pathophysiological processes remain only partly understood. In this review we will describe the development of the adult human microbiome and discuss how the composition of the gut microbiota changes in response to modulating factors. The influence of short-chain fatty acids, bile acids, prebiotics, probiotics, antibiotics and microbial transplantation is discussed from studies using animal and human models. Ultimately, we aim to translate these findings into therapeutic pathways for obesity and T2DM in humans.     

First victim,later aggressor: How the intestinal microbiota drives the pro-inflammatory effects of dietary emulsifiers?

The intestinal tract is inhabited by a large and diverse community of bacteria, collectively referred to as the gut microbiota. Composed of 500–1000 distinct species, the intestinal microbiota plays an important role in immunity and metabolism. However, alterations in its composition are associated with a variety of inflammatory diseases including obesity, diabetes, and inflammatory bowel disease (IBD). Among many other factors, our diet impacts microbiota composition and function, in either beneficial or detrimental ways. In this addendum, we will discuss our recent findings on how dietary emulsifying agents can directly and detrimentally impact the microbiota, leading to inflammatory diseases and cancer.     

Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT)

Obesity is a global pandemic with immense health consequences for individuals and societies. Multiple factors, including environmental influences and genetic predispositions, are known to affect the development of obesity. Despite an increasing understanding of the factors driving the obesity epidemic, therapeutic interventions to prevent or reverse obesity are limited in their impact. Manipulation of the human gut microbiome provides a new potential therapeutic approach in the fight against obesity. Specific gut bacteria and their metabolites are known to affect host metabolism and feeding behaviour, and dysbiosis of this biosystem may lead to metabolic syndrome. Potential therapies to alter the gut microbiota to treat obesity include dietary changes, supplementation of the diet with probiotic organisms and prebiotic compounds that influence bacterial growth, and the use of faecal microbiota transplant, in which gut microbiota from healthy individuals are introduced into the gut. In this review, we examine the growing scientific evidence supporting the mechanisms by which the human gut microbiota may influence carbohydrate metabolism and obesity, and the various possible therapies that may utilize the gut microbiota to help correct metabolic dysfunction.     

Mechanisms underlying the resistance to diet-induced obesity in germ-free mice

The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.     

Targeting gut microbiota in obesity: effects of prebiotics and probiotics

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.     

The microbiome and obesity: Is obesity linked to our gut flora?

The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.     

Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.     

Melatonin prevents obesity through modulation of gut microbiota in mice

Excess weight and obesity are severe public health threats worldwide. Recent evidence demonstrates that gut microbiota dysbiosis contributes to obesity and its comorbidities. The body weight‐reducing and energy balancing effects of melatonin have been reported in several studies, but to date, no investigations toward examining whether the beneficial effects of melatonin are associated with gut microbiota have been carried out. In this study, we show that melatonin reduces body weight, liver steatosis, and low‐grade inflammation as well as improving insulin resistance in high fat diet (HFD)‐fed mice. High‐throughput pyrosequencing of the 16S rRNA demonstrated that melatonin treatment significantly changed the composition of the gut microbiota in mice fed an HFD. The richness and diversity of gut microbiota were notably decreased by melatonin. HFD feeding altered 69 operational taxonomic units (OTUs) compare with a normal chow diet (NCD) group, and melatonin supplementation reversed 14 OTUs to the same configuration than those present in the NCD group, thereby impacting various functions, in particular through its ability to decrease the Firmicutes‐to‐Bacteroidetes ratio and increase the abundance of mucin‐degrading bacteria Akkermansia, which is associated with healthy mucosa. Taken together, our results suggest that melatonin may be used as a probiotic agent to reverse HFD‐induced gut microbiota dysbiosis and help us to gain a better understanding of the mechanisms governing the various melatonin beneficial effects.     

Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases

The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a ‘holobiontic’ way. It turns out that the host’s diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host’s wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.