Modifications Of Gut Microbiota Research Articles

Healthy Dietary Pattern Cycling Affects Gut Microbiota and Cardiovascular Disease Risk Factors: Results from a Randomized Controlled Feeding Trial with Young, Healthy Adults.

Previous research demonstrates that adopting, abandoning, and re-adopting (i.e., cycling) a healthy dietary pattern (HDP) improved, reverted, and re-improved cardiovascular disease (CVD) risk factors. In addition, changes in CVD risk factors are associated with dietary modifications of gut microbiota. We sought to assess the effects of cycling an HDP on gut microbiota and CVD risk factors. Retrospectively, we used data from a randomized controlled, crossover trial with three 3-week controlled dietary interventions, each separated by a 5-week period of participant-chosen, uncontrolled food intake. Seventeen participants (10 males, 7 females, age 26 ± 4 years old, BMI 23 ± 3 kg/m2) all consumed intervention diets that followed healthy U.S.-style dietary patterns. Gut microbiota composition and cardiovascular risk factors were measured before and after each HDP. Repeatedly adopting and abandoning an HDP led to a cycling pattern of changes in the gut microbial community and taxonomic composition. During the HDP cycles, relative abundances of several bacterial taxa (e.g., Collinsella, Mediterraneibacter, Romboutsia, and Dorea) decreased and returned to baseline repeatedly. Similar HDP cycling occurred for multiple CVD risk factors (i.e., serum total cholesterol and LDL-C concentrations). Consistent negative associations were observed between changes in Mediterraneibacter or Collinsella and serum total cholesterol/HDL-C ratio. These results support previous findings that HDP cycling affected multiple CVD risk factors and expand the HDP cycling phenomenon to include several bacterial taxa. Young adults are encouraged to adopt and sustain a healthy dietary pattern to improve cardiovascular health, potentially through modifying gut microbiota composition.

Microbiota-gut-liver-brain axis and hepatic encephalopathy.

Hepatic encephalopathy (HE) is a clinical manifestation of neurological and psychiatric abnormalities that are caused by complications of liver dysfunction including hyperammonemia, hyperuricemia, and portal hypertension. Accumulating evidence suggests that HE could be reversed through therapeutic modifications of gut microbiota. Multiple preclinical and clinical studies have indicated that gut microbiome affects the physiological function of the liver, such as the regulation of metabolism, secretion, and immunity, through the gut-liver crosstalk. In addition, gut microbiota also influences the brain through the gut-brain crosstalk, altering its physiological functions including the regulation of the immune, neuroendocrine, and vagal pathways. Thus, key molecules that are involved in the microbiota-gut-liver-brain axis might be able to serve as clinical biomarkers for early diagnosis of HE, and could be effective therapeutic targets for clinical interventions. In this review, we summarize the pathophysiology of HE and further propose approaches modulating the microbiota-gut-liver-brain axis in order to provide a comprehensive understanding of the prevention and potential clinical treatment for HE with a microbiota-targeted therapy.

Role of gut microbiota and inflammatory factors in acute respiratory distress syndrome: a Mendelian randomization analysis.

Acute respiratory distress syndrome (ARDS) is a serious lung ailment marked by significant inflammation and damage in the alveoli and capillaries of the lungs. Recent research suggests a strong correlation between the onset and advancement of ARDS and an imbalance in the gut microbiota (GM). In this investigation, Mendelian randomization (MR) analysis was utilized, drawing on data from publicly accessible genome-wide association studies. The primary focus was on examining the interplay between GM, inflammatory factors (IFs) and ARDS. Instrumental variables were established through genetic modifications of GM and IFs. Various statistical analysis methods including the inverse-variance weighted model, MR-Egger method and Wald ratio test were applied for comprehensive data analysis. Eight bacterial taxa within the GM demonstrated a potential causal link with development of ARDS. Notably, the phylum Actinobacteria and the genus Intestinibacter exhibited a negative association with the risk of ARDS. However, Erysipelotrichales (id. 2,148), Victivallis (id. 2,256), Ruminococcaceae UCG014 (id. 11,371), Eubacterium ruminantium group (id. 11,340), Erysipelotrichaceae (id. 2,149) and Erysipelotrichia (id. 2,147) demonstrated a positive association with ARDS risk. Additionally, the study identified a potential causal relationship between the inflammatory factors interleukin-16 and C-C motif chemokine 3 with the occurrence of ARDS. This study strongly suggests that the interaction between gut microbiota (GM) and inflammatory factors (IFs) significantly contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). This underscores their crucial involvement in both the initiation and advancement of this severe lung disorder.

Diet-gut microbial interactions influence cancer immunotherapy.

The gut microbiome is involved in the absorption and metabolism of host nutrients and modulates the immune response, affecting the efficacy of immunotherapy for cancer. In patients receiving immunotherapy, appropriate modifications of gut microbiota are thought to improve therapeutic response. Of all the factors that influence the gut microbiota, diet is the most influential and modifiable. Healthy dietary patterns as well as some specific dietary components can help the growth of beneficial microbiota in the gut, thereby protecting against cancers and promoting human health. A growing number of researches have confirmed the positive effects of a diet-gut microbiota approach as an adjuvant therapy for cancer, but controversy remains. Here, we summarize the interactions between diet and gut microbes based on previous studies, and discuss the role of gut microbiota-based dietary strategies in tumor immunotherapy, with the potential mechanisms of actions also intensively discussed.

Inulin increases the beneficial effects of rhubarb supplementation on high-fat high-sugar diet-induced metabolic disorders in mice: impact on energy expenditure, brown adipose tissue activity, and microbiota

ABSTRACT Consumption of prebiotics and plant-based compounds have many beneficial health effects through modulation of gut microbiota composition and are considered as promising nutritional strategy for the treatment of metabolic diseases. In the present study, we assessed the separated and combined effects of inulin and rhubarb on diet-induced metabolic disease in mice. We showed that supplementation with both inulin and rhubarb abolished the total body and fat mass gain upon high-fat and high-sucrose diet (HFHS) as well as several obesity-associated metabolic disorders. These effects were associated with increased energy expenditure, lower whitening of the brown adipose tissue, higher mitochondria activity and increased expression of lipolytic markers in white adipose tissue. Despite modifications of intestinal gut microbiota and bile acid compositions by inulin or rhubarb alone, combination of both inulin and rhubarb had minor additional impact on these parameters. However, the combination of inulin and rhubarb increased the expression of several antimicrobial peptides and higher goblet cell numbers, thereby suggesting a reinforcement of the gut barrier. Together, these results suggest that the combination of inulin and rhubarb in mice potentiates beneficial effects of separated rhubarb and inulin on HFHS-related metabolic disease and could be considered as nutritional strategy for the prevention and treatment of obesity and related pathologies.

Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications of gut microbiota seem to be associated with the disease, but the impact of gut microbiota on therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has been addressed, particularly on the Th17/Treg cells balance. Our study aimed to evaluate in early RA (ERA) patients compared to a control group, fecal gut microbiota composition, short-chain fatty acids concentrations, and the levels of circulating Th17/Treg and their own cytokines, before and after 3 months of standard treatment (Methotrexate (MTX) plus glucocorticoids). Fecal microbiota characterization was carried out on 19 ERA patients and 20 controls matched for sex and age. Significant decreased biodiversity levels, and a partition on the base of the microbiota composition, between the ERA patients at baseline compared to controls, were observed. The co-occurrent analysis of interactions revealed a characteristic clustered structure of the microbial network in controls that is lost in ERA patients where an altered connection between microbes and clinical parameters/metabolites has been reported. Microbial markers such as Acetanaerobacterium elongatum, Cristiansella massiliensis, and Gracilibacter thermotolerans resulted significantly enriched in control group while the species Blautia gnavus emerged to be more abundant in ERA patients. Our results showed an alteration in Th17/Treg balance with higher Th17 levels and lower Treg levels in ERA group respect to control at baseline, those data improved after therapy. Treatment administration and the achievement of a low disease activity/remission appear to exert a positive pressure on the structure of intestinal microbiota with the consequent restoration of biodiversity, of the structure of microbial network, and of the abundance of taxa that became closer to those presented by the subject without the disease. We also found an association between Blautia gnavus and ERA patients characterized by a significant reduction of propionic acid level. Furthermore significant differences highlighted at baseline among controls and ERA patients are no more evident after treatment. These data corroborate the role played by gut microbiota in the disease and suggest that therapy aimed to restore gut microbiota would improve treatment outcome.

Role of gut-kidney axis in renal diseases and IgA nephropathy.

Growing evidence show the importance of gut/kidney axis in renal diseases. Advances in gut microbiome sequencing, associated metabolites, detection of gut permeability and inflammation provide new therapeutic strategies targeting gut for kidney diseases and particularly for Immunoglobulin A (IgA) nephropathy (IgAN). The diversity and composition of gut flora have been recently deeply explored in kidney diseases. Modulation and depletion of microbiota in animal models allowed the understanding of molecular mechanisms involved in the crosstalk between gut, immune system and kidney. New clinical trials in order to positively modulate microbiota result in improvement of gastrointestinal disorders and inflammation in patients suffering with kidney diseases. The investigation of gut alterations in kidney diseases open new therapeutic strategies. In IgAN, targeted treatments for intestinal inflammation and modifications of gut microbiota seem promising.

Effects of the antibiotic rifaximin on cortical functional connectivity are mediated through insular cortex

It is well-known that antibiotics affect commensal gut bacteria; however, only recently evidence accumulated that gut microbiota (GM) can influence the central nervous system functions. Preclinical animal studies have repeatedly highlighted the effects of antibiotics on brain activity; however, translational studies in humans are still missing. Here, we present a randomized, double-blind, placebo-controlled study investigating the effects of 7 days intake of Rifaximin (non-absorbable antibiotic) on functional brain connectivity (fc) using magnetoencephalography. Sixteen healthy volunteers were tested before and after the treatment, during resting state (rs), and during a social stressor paradigm (Cyberball game—CBG), designed to elicit feelings of exclusion. Results confirm the hypothesis of an involvement of the insular cortex as a common node of different functional networks, thus suggesting its potential role as a central mediator of cortical fc alterations, following modifications of GM. Also, the Rifaximin group displayed lower connectivity in slow and fast beta bands (15 and 25 Hz) during rest, and higher connectivity in theta (7 Hz) during the inclusion condition of the CBG, compared with controls. Altogether these results indicate a modulation of Rifaximin on frequency-specific functional connectivity that could involve cognitive flexibility and memory processing.

Modifications of gut microbiota are associated with the severity of IgA nephropathy in the Chinese population

Immunoglobulin A nephropathy (IgAN) is a common glomerular disease. The pathogenesis of IgAN is associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a role in IgAN remains unclear. Blood and faecal samples were collected from 52 patients with IgAN and 25 healthy controls (HCs). The gut microbiome was analysed using the 16S ribosomal RNA gene. The levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor α (TNF-α), interleukin-1, and C-reactive protein were quantified. Substantial differences in the gut microbiota were identified between patients with IgAN and HCs (P < 0.05). Bacteroides and Escherichia-Shigella levels were significantly higher in patients with IgAN than in HCs, while Bifidobacterium and Blautia spp. Levels were lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in patients with IgAN with high urine RBC count (≥10/HP) and proteinuria (≥1 g/24 h) levels. Correlation analysis was used to assess the association between gut microbiota and biomarkers in patients with IgAN. The results showed that Prevotella 7 levels were negatively correlated with Gd-IgA1, LBP, sCD14, ICAM-1, and TNF-α levels, while Bifidobacterium spp. Levels presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella levels were negatively correlated with Prevotella 7. In patients with IgAN, gut modifications were characterised by an increase in the number of pathogenic bacteria and a reduction in the levels of beneficial bacteria, suggesting that the disturbance of intestinal microflora might be important in the severity of IgAN.

Modifications of Gut Microbiota after Grape Pomace Supplementation in Subjects at Cardiometabolic Risk: A Randomized Cross-Over Controlled Clinical Trial.

Polyphenols are dietary bioactive compounds able to induce modifications in the gut microbiota profile, although more clinical studies are needed. With this aim, a randomized cross-over clinical trial was conducted, where 49 subjects at cardiometabolic risk (exhibiting at least two metabolic syndrome factors) were supplemented with a daily dose of 8 g of grape pomace (GP) for 6 weeks, with an equivalent control (CTL) period. The levels of total bacteria and Bacteroidetes, Firmicutes, Lactobacilliales, Bacteroides and Prevotella were estimated in fecal DNA by quantitative real-time PCR (qPCR), while fecal short-chain fatty acids (SCFAs) were assessed by gas chromatography. Several cardiometabolic markers were evaluated in blood samples. GP reduced insulin levels only in half of the participants (responders). GP supplementation did not cause significant modifications in the microbiota profile of the whole group, except for a tendency (p = 0.059) towards a decrease in the proportion of Lactobacilliales, while it increased the proportion of Bacteroides in non-responder subjects. The reduction of insulin levels in subjects at cardiometabolic risk upon GP supplementation appears not to be induced by changes in the major subgroups of gut microbiota. Further studies at the species level may help to elucidate the possible role of microbiota in GP-induced insulinemic status.

Evolution of Gut Microbiome and Metabolome During Suspected Necrotizing Enterocolitis (NEC-1): A Case-Control Study

Necrotizing enterocolitis (NEC) is a devastating condition of the preterm new-born due to multiple factors, including gut microbiota dysbiosis. Since NEC development is poorly understood due to main focus on more severe NEC (NEC-2/3), we studied the gut microbiota and metabolome evolution of of children with suspected NEC (NEC-1). NEC-1 gut microbiota had a higher abundance of Streptococcus (second decade of life) and Staphylococcus (third decade of life) species. NEC-1 children showed a microbiome evolution in the third decade of life being the most divergent and associated to a different metabolomic signature than in healthy children. NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first decade of life and was more sensitive to factors such as childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life. The modifications of gut microbiota and microbiome during NEC-1 development appear more distinguishable by the third decade of life, when compared to healthy children. These data identify a precise window of time (i.e. third decade of life) and provide microbial targets to fight/blunt the progression of NEC-1. Funding Statement: This study was in part supported by the company Longevie SA in the persons of Michel LOSETO and Enzo LOSETO, as a donation to M.S. Longevie SA was not involved in any discussion nor provided any opinion on any part of this manuscript. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved (number of the approval: DC 2016-2804) by Neonatal and Pediatric Intensive Care Unit and Neonatology Department of Purpan Hospital in Toulouse, France. The parents of the children involved in this study gave their approval by written consensus.

Proteome modifications of gut microbiota in mice with activity-based anorexia and starvation: Role in ATP production.

Activity-based anorexia (ABA) in rodents is a behavioral model of anorexia nervosa, characterized by negative energy balance, hyperactivity, and dysbiosis of gut microbiota. Gut bacteria are known to produce energy substrates including adenosine triphosphate (ATP) and acetate. The aim of this study was to determine whether ABA alters the proteome of gut microbiota relevant to ATP and acetate production. The ABA was developed in male mice and compared with food-restricted and ad libitum-fed conditions. Proteomic analysis of feces was performed using the two-dimentional gel electrophoresis and mass spectrometry. The in vitro ATP-producing capacity of proteins extracted from feces was assayed. Increased levels of the phosphoglycerate kinase, an ATP-producing glycolytic enzyme, was detected in feces of food-restricted mice and this enzyme was further increased in the ABA group. Starvation also upregulated several other proteins synthetized by order Clostridiales including Clostridiaceae and Lachnospiraceae families. No significant differences in the in vitro ATP-producing capacity by bacterial proteins from ABA, food-restricted, and ad libitum-fed control mice were found. However, plasma levels of acetate strongly tended to be increased in the activity groups including ABA mice. The data revealed that starvation in food-restricted and ABA mice induced proteome modification in gut bacteria favoring ATP production mainly by the order Clostridiales. However, this did not result in increased total ATP-production capacity by gut microbiota. These changes can be interpreted as an adaptation of specific gut bacteria to the host malnutrition beneficial for host survival.

Antibiotic pretreatment alleviates liver transplant damage in mice and humans.

Although modifications of gut microbiota with antibiotics (Abx) influence mouse skin and cardiac allografts, its role in orthotopic liver transplantation (OLT) remains unknown. We aimed to determine whether and how recipient Abx pretreatment may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. Mice (C57BL/6) with or without Abx treatment (10 days) were transplanted with allogeneic (BALB/c) cold-stored (18 hours) livers, followed by liver and blood sampling (6 hours). We divided 264 human OLT recipients on the basis of duration of pre-OLT Abx treatment into control (Abx-free/Abx <10 days; n = 108) and Abx treatment (Abx ≥10days; n = 156) groups; OLT biopsy (Bx) samples were collected 2 hours after OLT (n = 52). Abx in mice mitigated IRI-stressed OLT (IRI-OLT), decreased CCAAT/enhancer-binding protein homologous protein (CHOP) (endoplasmic reticulum [ER] stress), enhanced LC3B (autophagy), and inhibited inflammation, whereas it increased serum prostaglandin E2 (PGE2) and hepatic PGE2 receptor 4 (EP4) expression. PGE2 increased EP4, suppressed CHOP, and induced autophagosome formation in hepatocyte cultures in an EP4-dependent manner. An EP4 antagonist restored CHOP, suppressed LC3B, and recreated IRI-OLT. Remarkably, human recipients of Abx treatment plus OLT (Abx-OLT), despite severe pretransplantation clinical acuity, had higher EP4 and LC3B levels but lower CHOP levels, which coincided with improved hepatocellular function (serum aspartate aminotransferase/serum aspartate aminotransferase [sALT/sAST]) and a decreased incidence of early allograft dysfunction (EAD). Multivariate analysis identified "Abx-free/Abx <10 days" as a predictive factor of EAD. This study documents the benefits of Abx pretreatment in liver transplant recipients, identifies ER stress and autophagy regulation by the PGE2/EP4 axis as a homeostatic underpinning, and points to the microbiome as a therapeutic target in OLT.

Vitamin K–what is known regarding bariatric surgery patients: a systematic review

Vitamin K, a fat-soluble vitamin, is involved in blood coagulation, bone mineralization, inhibition of vascular calcification, and regulation of numerous enzyme systems. Patients who undergo bariatric surgery (BS), especially procedures that involve a malabsorptive component, are prone to develop vitamin K deficiency (VKD). The causes of VKD include decreased absorptive surface areas, steatorrhea, bacterial overgrowth, marked reduction of carriers of vitamin K, decrease in vitamin K intake, and modifications of gut microbiota. Data on vitamin K status among BS patients are scarce and the strength of evidence supporting vitamin K supplementation is weak. Thus, this systematic review summarized the scientific literature on vitamin K and examined the status among patients before and after BS, as well as among pregnant women with a history of BS. A MEDLINE/Pubmed and Embase electronic search was performed. After a thorough screening of 204 titles, 19 articles were selected by 2 independent reviewers. Five studies on BS candidates (n = 750), 12 studies after BS (n = 1442), and 4 studies on pregnant woman after BS (n = 83, of them n = 7 from case reports) were included. Results of the current review suggest that patients who undergo major malabsorptive surgeries are at a higher risk of developing VKD and should be better monitored. At this point, it is still unclear whether supplementation of vitamin K is required, and what oral dose or vitamer type should be used to normalize serum levels after different types of bariatric procedures. It should be noted that the current protocols for VKD treatment are still experiential in these patients. It is also unknown at what intervals screening tests for vitamin K should be performed and what assay is most appropriate for screening purposes. Future studies are needed to answer these unresolved issues.

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 10weeks postoperatively. Associations between discriminating genera and metabolic markers after RYGB were explored. The 2 procedures induced similar glucose improvement and increased flora diversity after 10weeks 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.

Alteration of intestinal permeability: the missing link between gut microbiota modifications and inflammation in obesity?

The increasing incidence of obesity and associated metabolic complications is a worldwide public health issue. The role of the gut in the pathophysiology of obesity, with an important part for microbiota, is becoming obvious. In rodent models of diet-induced obesity, the modifications of gut microbiota are associated with an alteration of the intestinal permeability increasing the passage of food or bacterial antigens, which contribute to low-grade inflammation and insulin resistance. In human obesity, intestinal permeability modification, and its role in the crosstalk between gut microbiota changes and inflammation at systemic and tissular levels, are still poorly documented. Hence, further characterization of the triggering mechanisms of such inflammatory responses in obese subjects could enable the development of personalized intervention strategies that will help to reduce the risk of obesity-associated diseases.

Effects of a Symbiotic on Gut Microbiota in Mexican Patients With End-Stage Renal Disease

Gut microbiota provides beneficial effects under physiological conditions, but is able to contribute to inflammatory diseases in susceptible individuals. Thus, we designed this study to test whether additional intake of symbiotic gel affects specific modifications of gut microbiota in patients with end-stage renal disease (ESRD). Eighteen patients with ESRD diagnosis with renal replacement therapy (hemodialysis) were included in this study. They were randomly assigned to 2 treatment groups: (1) test group (nutritional counseling+symbiotic) and (2) control group (nutritional counseling+placebo). Clinical history and the evaluation of Gastrointestinal Symptom Rating Scale were performed. Gut microbiota composition was analyzed by real-time polymerase chain reaction from fecal samples. All subjects were followed for 2months. Bifidobacterial counts were higher in the second samples (mean: 5.5±1.72 log10 cells/g) than in first samples (4.2±0.88 log 10cells/g) in the patients of the test group (P=.0344). Also, lactobacilli counts had a little decrease in the test group (2.3±0.75 to 2.0±0.88 log 10 cells/g) and the control group (2.2±0.90 to 1.8±1.33 log 10 cells/g), between the first and the second samples. Gastrointestinal symptoms scores (scale 8-40) were reduced in the test group (start 12 [10-14] and end 9 [8-10]) compared with control group (start 11 [8-21] and end 11 [9-15]). Short-term symbiotic treatment in patients with ESRD can lead to the increase of Bifidobacterium counts, maintaining the intestinal microbial balance.

Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes

Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for treating morbid obesity and results in weight-loss and improvements in metabolism and inflammation. We examined the impact of RYGB on modifications of gut microbiota and its potential associations with changes in gene expression in white adipose tissue (WAT). Gut microbiota were profiled from fecal samples by using pyrosequencing in morbidly obese individuals, explored before (0 mo), 3 mo after, and 6 mo after RYGB. WAT gene expression was studied at 0 and 3 mo. We explored associations between microbial genera and differentially expressed genes in WAT and clinical markers. The richness of gut microbiota increased after RYGB; 37% of increased bacteria belonged to Proteobacteria. The associations between gut microbiota composition and WAT gene expression increased after RYGB. Fourteen discriminant bacterial genera (7 were dominant and 7 were subdominant) and 202 WAT genes changed after RYGB. Variations in bacterial genera correlated with changes in both clinical phenotype and adipose tissue gene expression. Some genes encode metabolic and inflammatory genes. Almost half of the correlations were independent of the change in calorie intake. These results show an increase in gut microbiota richness and in the number of associations between gut microbiota and WAT genes after RYGB in obesity. Variations of gut microbiota were associated with changes in WAT gene expression. These findings stimulate deeper explorations of the mechanisms linking gut microbiome and WAT pathological alterations in human obesity and its changes after weight loss.

Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes

The prevalence of obesity, insulin resistance and type 2 diabetes has steadily increased in the last decades. In addition to the genetic and environmental factors, gut microbiota may play an important role in the modulation of intermediary phenotypes leading to metabolic disease. Obesity and type 2 diabetes are associated with specific changes in gut microbiota composition. The mechanisms underlying the association of specific gut microbiota and metabolic disease include increasing energy harvest from the diet, changes in host gene expression, energy expenditure and storage, and alterations in gut permeability leading to metabolic endotoxemia, inflammation and insulin resistance. In some studies, the modifications of gut microbiota induced by antibiotics, prebiotics and probiotics led to improved inflammatory activity in parallel to amelioration of insulin sensitivity and decreased adiposity. However, these effects were mainly observed in animal models. Their extrapolation to humans awaits further studies. The fascinating role of gut microbiota on metabolic disease opens new avenues in the treatment of obesity, insulin resistance and type 2 diabetes. A co-evolutionary clue for microbiota and insulin resistance is suggested.

Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss

OBJECTIVEObesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure.RESEARCH DESIGN AND METHODSGut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB.RESULTSFour major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at M0 and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at M0 and throughout the follow-up after surgery independently of changes in food intake.CONCLUSIONSThese results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake.