Gut bacterial microbiota and obesity

Although probiotics and antibiotics have been used for decades as growth promoters in animals, attention has only recently been drawn to the association between the gut microbiota composition, its manipulation, and obesity. Studies in mice have associated the phylum Firmicutes with obesity and the phylum Bacteroidetes with weight loss. Proposed mechanisms linking the microbiota to fat content and weight include differential effects of bacteria on the efficiency of energy extraction from the diet, and changes in host metabolism of absorbed calories. The independent effect of the microbiota on fat accumulation has been demonstrated in mice, where transplantation of microbiota from obese mice or mice fed western diets to lean or germ-free mice produced fat accumulation among recipients. The microbiota can be manipulated by prebiotics, probiotics, and antibiotics. Probiotics affect the microbiota directly by modulating its bacterial content, and indirectly through bacteriocins produced by the probiotic bacteria. Interestingly, certain probiotics are associated with weight gain both in animals and in humans. The effects are dependent on the probiotic strain, the host, and specific host characteristics, such as age and baseline nutritional status. Attention has recently been drawn to the association between antibiotic use and weight gain in children and adults. We herein review the studies describing the associations between the microbiota composition, its manipulation, and obesity.     

Gut microbiome and metabolic diseases

The prevalence of obesity and obesity-related disorders is increasing worldwide. In the last decade, the gut microbiota has emerged as an important factor in the development of obesity and metabolic syndrome, through its interactions with dietary, environmental, and host genetic factors. Various studies have shown that alteration of the gut microbiota, shifting it toward increased energy harvest, is associated with an obese phenotype. However, the molecular mechanisms by which the gut microbiota affects host metabolism are still obscure. In this review, we discuss the complexity of the gut microbiota and its relationship to obesity and obesity-related diseases. Furthermore, we discuss the anti-obesity potential of probiotics and prebiotics.     

Antibiotic Treatment of Pregnant Non‐Obese Diabetic Mice Leads to Altered Gut Microbiota and Intestinal Immunological Changes in the Offspring

The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non‐obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut‐related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development.     

Gut microbiome production of short-chain fatty acids and obesity in children

Obesity has been a worldwide multifactorial epidemic malady for the last 2 decades. Changes in gut microbiota composition and its metabolites — short-chain fatty acids (SCFAs) — have been associated with obesity. Recent evidence suggests that SCFAs made by the gut microbiota may regulate directly or indirectly physiological and pathological processes in relation to obesity. We review the influence of gut microbiota in energy, glucose, and lipid homeostasis control via their metabolites. Gut microbial disturbances in obese children may have a role in their metabolism. At first glance, excessive short-chain fatty acids produced by a particular gut microbiota represent an additional energy source, and should cause an imbalance in energy regulation, contributing to obesity. However, simultaneously, SCFA participates in glucose-stimulated insulin secretion from the pancreatic β-cells through interaction with the FFA2 and FFA3 receptors, and release of peptide hormones which control appetite. This apparent contradictory situation may indicate the involvement of additional particular bacteria or bacterial components or metabolites that may trigger regulatory cascades by interaction with some G-protein-coupled membrane receptors.     

Human microbiome restoration and safety

The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.     

The intricate association between gut microbiota and development of Type 1, Type 2 and Type 3 diabetes

It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer’s disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer’s disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general.     

Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity?

Current evidence supports a role for gut colonization in promoting and maintaining a balanced immune response in early life. An altered or less diverse gut microbiota composition has been associated with atopic diseases, obesity, or both. Moreover, certain gut microbial strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. However, there has been no fully adequate longitudinal study of the relation between the neonatal gut microbiota and the development of allergic diseases (eg, atopic asthma) and obesity. The emergence of promising experimental studies has led to several clinical trials of probiotics (live bacteria given orally that allow for intestinal colonization) in human subjects. Probiotic trials thus far have failed to show a consistent preventive or therapeutic effect on asthma or obesity. Previous trials of probiotics have been limited by small sample size, short duration of follow-up, or lack of state-of-the art analyses of the gut microbiota. Finally, there is emerging evidence that the vitamin D pathway might be important in gut homeostasis and in signaling between the microbiota and the host. Given the complexity of the gut micriobiota, additional research is needed before we can confidently establish whether its manipulation in early life can prevent or treat asthma, obesity, or both.     

Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding

A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism. The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a "microbial organ" localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.     

Interaction between gut microbiota and toll-like receptor: from immunity to metabolism

The human gut contains trillions of commensal bacteria, and similar to pathogenic bacteria, the gut microbes and their products can be recognized by toll-like receptors (TLRs). It is well acknowledged that the interaction between gut microbiota and the local TLRs help to maintain the homeostasis of intestinal immunity. High-fat intake or obesity can weaken gut integrity leading to the penetration of gut microbiota or their bacterial products into the circulation, leading to the activation of TLRs on immune cells and subsequently low-grade systemic inflammation in host. Metabolic cells including hepatocytes and adipocytes also express TLRs. Although they are able to produce and secrete inflammatory molecules, the effectiveness remains low compared with the immune cells embedded in the liver and adipose tissue. The interaction of TLRs in these metabolic cells or organs with gut microbiota remains unclear, but a few studies have suggested that the functions of these TLRs are related to metabolism. Alteration of the gut microbiota is associated with body weight change and adiposity in human, and the interaction between the commensal gut microbiota and TLRs may possibly involve both metabolic and immunological regulation. In this review, we will summarize the current findings on the relationship between TLRs and gut microbiota with a focus on metabolic regulation and discuss how such interaction participates in host metabolism.     

Frequency of Firmicutes and Bacteroidetes in gut microbiota in obese and normal weight Egyptian children and adults

Introduction

Obesity and associated metabolic disorders are a worldwide epidemic. Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. The aim of this study was to assess the differences in the composition of the intestinal microbiota between obese and normal weight Egyptian children and adults.

Material and methods

The study included 79 subjects among whom 51 were obese (23 children and 28 adults), and 28 were subjects of normal weight (17 children and 11 adults). Faecal samples were collected from all subjects. Total DNA was extracted from collected stool samples and submitted to conventional PCR for detection of Firmicutes and Bacteroidetes. All the studied group was subjected to clinical and anthropometric evaluation. Laboratory assessment of fasting glucose, high-sensitivity C-reactive protein (hsCRP) and lipid profile was performed.

Results

The proportions of the phyla Firmicutes and Bacteroidetes were statistically significantly increased in the obese group compared to the normal weight group (p < 0.001, p = 0.003 respectively). The study also found a statistically significant positive trend for higher hsCRP in subjects with positive Firmicutes (p = 0.004). However, no associations were found between positive Bacteroidetes and hsCRP.

Conclusions

The results of this study indicate that obesity in Egyptian children and adults is associated with compositional changes in faecal microbiota with increase in the phyla Firmicutes and Bacteroidetes. This could be considered when developing strategies to control obesity and its associated diseases by modifying the gut microbiota.     

肠道菌群在妊娠期糖尿病发病中作用的研究进展

肠道菌群对引发妊娠期糖尿病(GDM)具有重要作用.肠道菌群通过对肠道黏膜屏障的破坏,释放代谢产物、引起脂肪因子和炎性因子的释放及影响肠道免疫功能等方式导致胰岛素抵抗及分泌水平下降,血糖稳态失衡,最终引发GDM.益生菌可以有效改善GDM患者的肠道菌群失调及血糖的紊乱,从而改善妊娠结局.     

Immune homeostasis,dysbiosis and therapeutic modulation of the gut microbiota

The distal gut harbours ∼10¹³ bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host–microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery

Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.Key Words: Obesity, Type 2 diabetes, Metabolic surgery, Hyperinsulinemia, Insulin resistance, Surgical food restriction, Incretins     

Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study

The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants. In particular, the colonization of preterm infants by bifidobacteria is delayed. A double-blind, placebo-controlled, randomized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota. Both culture-dependent and culture-independent approaches were used to study the gut microbiota. Bifidobacterial numbers, determined by fluorescence in situ hybridization, were significantly higher in the probiotic than in the placebo group (log(10) values per g of fecal wet weight: probiotic, 8.18 + 0.54 [standard error of the mean]; placebo, 4.82 + 0.51; P < 0.001). A similar trend for bifidobacterial numbers was also obtained with the culture-dependent method. The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae (log(10) values of CFU per g of fecal wet weight: probiotic, 7.80 + 0.34; placebo, 9.03 + 0.35; P = 0.015) and Clostridium spp. (probiotic, 4.89 + 0.30; placebo, 5.99 + 0.32; P = 0.014) than the infants in the placebo group. Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population. However, the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia.     

Dietary soyasaponin attenuates 2,4-dinitrofluorobenzene-induced contact hypersensitivity via gut microbiota in mice

Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic contact dermatitis (ACD); however, their therapeutic mechanisms remain unknown. Here, we attempted to clarify the role of gut microbiota in the inhibition of CHS by dietary soyasaponins. For antibiotic treatment, mice were administered a mixture of ciprofloxacin and metronidazole or vancomycin. These antibiotics and SSs were given to mice via drinking water 3-weeks prior to CHS induction with 2,4-dinitrofluorobenzene, and the mice were analysed for ear swelling, tissue oedema, infiltration of Gr-1-positive immune cells, the composition of faecal microbiota and regulatory T (T_reg) cells. The soyasaponin diets attenuated ear swelling and tissue oedema, and reduced the number of Gr-1-positive cells infiltrating ear tissues. CHS caused changes in the structure of the gut microbiota, but dietary SSs blocked the changes in the microbiota composition. Ciprofloxacin and metronidazole treatments significantly enhanced the severity of CHS symptoms, whereas vancomycin treatment blocked the suppressive effect of dietary SSs on CHS. These antibiotic treatments differed in their effects on the gut microbiota composition. T_reg cells in auricular lymph node and spleen increased under SS-enriched diets, but this increase was blocked by vancomycin treatment. These results suggest that dietary SSs exert their inhibitory activity on CHS via the gut microbiota in mice, suggesting that dietary supplementation with SSs may have beneficial effects on ACD patients, but that the gut microbiota is a critical determinant of the therapeutic value of dietary SSs.     

Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge

Recent studies have shown that the human fecal microbiota is composed of a consortium of species specific to the host and resistant to modifications over time. Antibiotics are known to affect the intestinal microflora, and ensuing changes may result in antibiotic-associated diarrhea. It is therefore important to characterize the nature and amplitude of these modifications and the ability of this ecosystem to return to its original profile-i.e., its resilience. Six healthy volunteers received oral amoxicillin (1.5 g/day) for 5 days. Fecal samples were collected at day 0 (D0) before antibiotic treatment and at set intervals until 60 days thereafter. Fecal DNA was isolated, and V6-to-V8 regions of the 16S rRNA genes were amplified by PCR with general primers and analyzed by temporal temperature gradient gel electrophoresis. Dominant species profiles were compared on the basis of similarity (Pearson correlation coefficient). Dominant species profiles at D0 were used as a reference. The fecal microbiota showed a major shift in dominant species upon antibiotic treatment, starting 24 h after treatment initiation and reaching an average similarity of only 74% after 4 days. Within 30 days following antibiotic treatment, the fecal microbiota tended to reach an average similarity of 88% to the D0 value; within 60 days, the average similarity to the D0 value was 89%. However, in one subject, important modifications persisted for at least 2 months, with similarity to the D0 value remaining below 70%. We demonstrated the resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. Yet the persistence of long-term alterations in some subjects may explain susceptibilities to antibiotic-associated diarrhea. Furthermore, these findings suggest that strategies reinforcing the ability of the fecal microbiota to resist modifications would be of clinical relevance.     

The ''microflora hypothesis'' of allergic diseases

Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in 'industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this 'microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a 'balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.