Gut microbiome: Linking together obesity,bariatric surgery and associated clinical outcomes under a single focus

Obesity is increasingly prevalent in the post-industrial era, with increased mortality rates. The gut microbiota has a central role in immunological, nutritional and metabolism mediated functions, and due to its multiplexity, it is considered an independent organ. Modern high-throughput sequencing techniques have allowed phylogenetic exploration and quantitative analyses of gut microbiome and improved our current understanding of the gut microbiota in health and disease. Its role in obesity and its changes following bariatric surgery have been highlighted in several studies. According to current literature, obesity is linked to a particular microbiota profile that grants the host an augmented potential for calorie release, while limited diversity of gut microbiome has also been observed. Moreover, bariatric surgery procedures represent effective interventions for sustained weight loss and restore a healthier microbiota, contributing to the observed fat mass reduction and lean mass increase. However, newer evidence has shown that gut microbiota is only partially recovered following bariatric surgery. Moreover, several targets including FGF15/19 (a gut-derived peptide), could be responsible for the favorable metabolic changes of bariatric surgery. More randomized controlled trials and larger prospective studies that include well-defined cohorts are required to better identify associations between gut microbiota, obesity, and bariatric surgery.     

Fasting intervention and its clinical effects on the human host and microbiome

Experimental trials in organisms ranging from yeast to humans have shown that various forms of reducing food intake (caloric restriction) appear to increase both overall and healthy lifespan, delaying the onset of disease and slowing the progression of biomarkers of aging. The gut microbiota is considered one of the key environmental factors strongly contributing to the regulation of host health. Perturbations in the composition and activity of the gut microbiome are thought to be involved in the emergence of multiple diseases. Indeed, many studies investigating gut microbiota have been performed and have shown strong associations between specific microorganisms and metabolic diseases including overweight, obesity, and type 2 diabetes mellitus as well as specific gastrointestinal disorders, neurodegenerative diseases, and even cancer. Dietary interventions known to reduce inflammation and improve metabolic health are potentiated by prior fasting. Inversely, birth weight differential host oxidative phosphorylation response to fasting implies epigenetic control of some of its effector pathways. There is substantial evidence for the efficacy of fasting in improving insulin signaling and blood glucose control, and in reducing inflammation, conditions for which, additionally, the gut microbiota has been identified as a site of both risk and protective factors. Accordingly, human gut microbiota, both in symbiont and pathobiont roles, have been proposed to impact and mediate some health benefits of fasting and could potentially affect many of these diseases. While results from small-N studies diverge, fasting consistently enriches widely recognized anti-inflammatory gut commensals such as Faecalibacterium and other short-chain fatty acid producers, which likely mediates some of its health effects through immune system and barrier function impact.     

The gut microbiota and metabolic disease: current understanding and future perspectives

The human gut microbiota has been studied for more than a century. However, of nonculture‐based techniques exploiting next‐generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short‐chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate‐producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate‐producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long‐term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target.     

Gut microbiota after Roux‐en‐Y gastric bypass and sleeve gastrectomy in a diabetic rat model: Increased diversity and associations of discriminant genera with metabolic changes

Recent work with gut microbiota after bariatric surgery is limited, and the results have not been in agreement. Given the role of the gut microbiota in regulating host metabolism, we explored the effect of Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the modifications of gut microbiota with regard to the potential influence of food intake and/or weight loss and examined their links with host metabolism. Zucker diabetic fatty rats were divided into the following groups: RYGB; sham‐operated with pair‐fed as RYGB; sham‐operated fed ad libitum ; and SG. The metabolic effects and gut microbiota profile were analyzed 10 weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10 weeks compared with sham‐operated groups. RYGB induced a marked higher relative abundance of Proteobacteria/Gammaproteobacteria and Betaproteobacteria and increased emergence of Fusobacteria and Clostridium, whereas SG resulted in more abundant Actinobacteria compared with other groups. Most of the 12 discriminant genera correlated with changes in metabolic phenotype, but only 28.6% of these correlations were independent of weight, and 4 discriminant genera still negatively correlated with serum insulin level independent of food intake and weight loss after RYGB. These data demonstrate that RYGB and SG surgery produced similar diversity but different microbiota compositions changes in Zucker diabetic fatty rats. These findings stimulate deeper explorations of functions of the discriminate microbiota and the mechanisms linking postsurgical modulation of gut microbiota and improvements in insulin resistance.     

Personality traits and obesity: a systematic review

Based on a bio‐social‐ecological systems model of the development and maintenance of obesity, there has been in the last few years a growing research interest in the association of obesity and personality traits. The aim of the present review was a comprehensive and critical evaluation of the existing literature taking into account the methodological quality of studies to enhance our understanding of personality traits associated with body weight, the development of overweight and obesity as well as the effectiveness of weight loss interventions including bariatric surgery. Personality traits play an important role both as risk as well as protective factors in the development of overweight and obesity. While thus in particular ‘neuroticism’, ‘impulsivity’ and ‘sensitivity to reward’ appear as risk factors, ‘conscientiousness’ and ‘self‐control’ have been shown to have a protective function in relation to weight gain. Conscientiousness is a measure of regulation of internal urges and self‐discipline, and may thus provide a potential source of control over impulsive reward‐oriented behaviour. The results of the present review suggest that, within the context of therapeutic weight reduction measures, it is meaningful to identify subgroups of patients for whom specific treatment options need to be developed, such as measures for strengthening self‐control skills.     

Gut microbiota and metabolic syndrome

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome,as confirmed by studies conducted both on humans and animal models.Gut microbial composition and functions are strongly influenced by diet.This complex intestinal“superorganism”seems to affect host metabolic balance modulating energy absorption,gut motility,appetite,glucose and lipid metabolism,as well as hepatic fatty storage.An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of“metabolic endotoxemia”,leading to systemic inflammation and insulin resistance.Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition,that seem to affect the success,or the inefficacy,of treatment strategies.Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity,thus,ameliorating metabolic balance and promoting weight loss.However,further evidence is needed to better understand their clinical impact and therapeutic use.     

Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.     

Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

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.     

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.     

The Role of the Manipulation of the Gut Microbiota in Obesity

The manipulation of the gut microbiota by diet, antibiotics, or probiotics could promote, prevent, or reverse the development of specific diseases, including obesity. A link has been proposed between obesity and the growth promoters (probiotics and antibiotics) that have been used in animals for more than 40 years to induce weight gain. Several species of the Lactobacillus genus that are frequently used as probiotics for human consumption merit particular attention because they are increased in the gut microbiota under high-fat diets, are more abundant in obese humans, and are selected by growth-promoter antibiotics; moreover, the administration of these bacteria in experimental models is linked to the development of obesity. However, other species or strains of the same genus are associated with an antiobesity effect. Newborns and infants are a particularly susceptible population in which the administration of antibiotics or probiotics could be related to the development of obesity in adulthood.     

Obesity,diabetes, and the gut microbiome: an updated review

Introduction: Obesity and diabetes are two of the most prevalent health problems and leading causes of death globally. As research on the intestinal microbiome increases, so does our understanding of its intricate relationship to these diseases, although this has yet to be fully elucidated.

Areas covered: This review evaluates the role of the gut microbiome in obesity and diabetes, including the influences of internal and environmental factors. Literature searches were performed using the keywords ‘diabetes,’ ‘insulin resistance,’ ‘gut microbiome,’ ‘gut microbes,’ ‘obesity,’ and ‘weight gain.’

Expert commentary: Highlights of recent research include new findings regarding the effects of caloric restriction, which expound the importance of diet in shaping the gut microbiome, and studies reinforcing the lasting implications of antibiotic use for diabetes and obesity, particularly repeated doses in early childhood.

Mechanistically, interactions between the microbiome and the host innate immune system, mediated by TLR4-LPS signaling, have been shown to meditate the metabolic benefits of caloric restriction. Further, gut microbes haven now been shown to regulate oxygen availability via butyrate production, thus protecting against the proliferation of pathogens such as E. coli and Salmonella. However, many microbial metabolites remain unidentified and their roles in obesity and diabetes remain to be determined.     

Diet approach before and after bariatric surgery

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5–10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

     

Current status of bariatric surgery in the treatment of type 2 diabetes

Bariatric surgery (from the Greek words baros meaning ‘weight’ and iatrikos‘the art of healing’) is a rapidly evolving branch of surgical science. The aim is to induce major weight loss in those whose obesity places them at high risk of serious health problems. In an attempt to balance the risks of surgery against the benefits of weight loss, bariatric operations are currently performed only in the morbidly obese, or those with a body mass index (BMI) > 35 kgm^?2 who already have developed comorbidity such as type 2 diabetes. Although weight loss is beneficial for obese patients with diabetes, current medical treatment for obesity is difficult. In contrast, observational studies show a major impact of bariatric surgery on diabetes, raising the question whether this approach should be used more widely to treat diabetes in obese patients? If bariatric surgery were shown to be the best way to treat diabetes in obese subjects the implications for health services would be wide‐ranging. Bariatric surgery leads to withdrawal of diabetic treatment in about 60% or more of patients, and reductions of therapy for many others. Although data on bariatric surgery in subjects with diabetes are provocative, most studies have been uncontrolled or flawed in other ways. Most importantly, bariatric surgery has not yet been compared against standard medical treatment for diabetes in randomized controlled trials with diabetes‐specific endpoints in all relevant patient groups. Potential indications for bariatric surgery are discussed, and the unanswered questions that need to be addressed by clinical trials are summarized. Although small numbers of patients may be interested in bariatric surgery for type 2 diabetes, current data are insufficient to endorse its wide scale use for this indication. Until essential studies are undertaken the role and economics of bariatric surgery in the diabetic clinic will remain uncertain.     

The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization

Objective:

The gut microbiota contribute otherwise impossible metabolic functions to the human host. Shifts in the relative proportions of gut microbial communities in adults have been correlated with intestinal disease and have been associated with obesity. The aim of this study was to elucidate differences in gut microbial compositions and metabolite concentrations of obese versus normal-weight children.

Materials and methods:

Fecal samples were obtained from obese (n=15; mean body mass index (BMI) s.d. score=1.95) and normal-weight (n=15; BMI s.d. score=−0.14) Swiss children aged 8–14 years. Composition and diversity of gut microbiota were analyzed by qPCR and temperature gradient gel electrophoresis (TGGE).

Results:

No significant quantitative differences in gut microbiota communities of obese and normal-weight children were identified. Microbial community profiling by TGGE revealed a high degree of both intra- and intergroup variation. Intergroup comparison of TGGE profiles failed to identify any distinct populations exclusive to either obese or normal-weight children. High-pressure liquid chromatography analysis identified significantly higher (P<0.05) concentrations of short-chain fatty acids (SCFA) butyrate and propionate in obese versus normal-weight children. Significantly lower concentrations of intermediate metabolites were detected in obese children, suggesting exhaustive substrate utilization by obese gut microbiota.

Conclusions:

Our results indicate that a dysbiosis may be involved in the etiology of childhood obesity. In turn, aberrant and overactive metabolic activity within the intestine could dictate survival or loss of individual microbial communities, leading to the altered population ratios previously identified in adult obesity.     

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.     

Role of gut microbiota,bile acids and their cross‐talk in the effects of bariatric surgery on obesity and type 2 diabetes

Type 2 diabetes mellitus is becoming increasingly prevalent worldwide, and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss, and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations, such as Roux‐en‐Y gastric bypass and sleeve gastrectomy, are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown. Those mechanical explanations, such as restriction and malabsorption, are challenged by accumulating evidence from human and animal models of these procedures, which points to the weight‐independent factors, such as hormones, bile acids, gut microbiota, nervous system and other potential underlying mechanisms. A growing body of evidence suggests that gut microbiota are associated with the development of several metabolic disorders, and bile acids and FXR signaling are important for the metabolic benefits of bariatric surgery. Given the close relationship between bacteria and bile acids, it is reasonable to propose that microbiota–bile acid interactions play a role in the mechanisms underlying the effects of metabolic surgery.     

Microbial and metabolic interactions between the gastrointestinal tract and Clostridium difficile infection

Antibiotics disturb the gastrointestinal tract microbiota and in turn reduce colonization resistance against Clostridium difficile. The mechanism for this loss of colonization resistance is still unknown but likely reflects structural (microbial) and functional (metabolic) changes to the gastrointestinal tract. Members of the gut microbial community shape intestinal metabolism that provides nutrients and ultimately supports host immunity. This review will discuss how antibiotics alter the structure of the gut microbiota and how this impacts bacterial metabolism in the gut. It will also explore the chemical requirements for C. difficile germination, growth, toxin production and sporulation. Many of the metabolites that influence C. difficile physiology are products of gut microbial metabolism including bile acids, carbohydrates and amino acids. To restore colonization resistance against C. difficile after antibiotics a targeted approach restoring both the structure and function of the gastrointestinal tract is needed.     

Strategies to increase the efficacy of using gut microbiota for the modulation of obesity

Obesity is one of the most serious global public health challenges of the 21st century. The adjustment of gut microbiota is often recommended as an efficient strategy to treat obesity. This modulation of gut microbiota can be performed by many methods, including dietary intervention, antibiotic application, the use of prebiotics and probiotics, bariatric surgery and faecal microbiota transplantation. In most cases, positive effects have been observed in response to treatment, but invalid and even contrary effects have also been observed in some cases due to factors that are unrelated to intervention methods, such as genetic factors, patient age or gender, environmental microbiota, climate, geography and lifestyle. These factors can cause variation of gut microbial populations and thus should also be taken into consideration when selecting modulation strategies.     

Gut microbial adaptation to dietary consumption of fructose,artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity

The Western diet, comprised of highly refined carbohydrates and fat but reduced complex plant polysaccharides, has been attributed to the prevalence of obesity. A concomitant rise in the consumption of fructose and sugar substitutes such as sugar alcohols, artificial sweeteners, even rare sugars, has mirrored this trend, as both probable contributor and solution to the epidemic. Acknowledgement of the gut microbiota as a factor involved in obesity has sparked much controversy as to the cause and consequence of this relationship. Dietary intakes are a known modulator of gut microbial phylogeny and metabolic activity, frequently exploited to stimulate beneficial bacteria, promoting health benefits. Comparably little research exists on the impact of ‘unconscious’ dietary modulation on the resident commensal community mediated by increased fructose and sugar substitute consumption. This review highlights mechanisms of potential host and gut microbial fructose and sugar substitute metabolism. Evidence is presented suggesting these sugar compounds, particularly fructose, condition the microbiota, resulting in acquisition of a westernized microbiome with altered metabolic capacity. Disturbances in host–microbe interactions resulting from fructose consumption are also explored.