Gut Microbiota and Predicted Metabolic Pathways in a Sample of Mexican Women Affected by Obesity and Obesity Plus Metabolic Syndrome.
ABSTRACT: Obesity is an excessive fat accumulation that could lead to complications like metabolic syndrome. There are reports on gut microbiota and metabolic syndrome in relation to dietary, host genetics, and other environmental factors; however, it is necessary to explore the role of the gut microbiota metabolic pathways in populations like Mexicans, where the prevalence of obesity and metabolic syndrome is high. This study identify alterations of the gut microbiota in a sample of healthy Mexican women (CO), women with obesity (OB), and women with obesity plus metabolic syndrome (OMS). We studied 67 women, characterizing their anthropometric and biochemical parameters along with their gut bacterial diversity by high-throughput DNA sequencing. Our results indicate that in OB or OMS women, Firmicutes was the most abundant bacterial phylum. We observed significant changes in abundances of bacteria belonging to the Ruminococcaceae, Lachnospiraceae, and Erysipelotrichaceae families and significant enrichment of gut bacteria from 16 different taxa that might explain the observed metabolic alterations between the groups. Finally, the predicted functional metagenome of the gut microbiota found in each category shows differences in metabolic pathways related to lipid metabolism. We demonstrate that Mexican women have a particular bacterial gut microbiota characteristic of each phenotype. There are bacteria that potentially explain the observed metabolic differences between the groups, and gut bacteria in OMS and OB conditions carry more genes of metabolic pathways implicated in lipid metabolism.
Project description:BACKGROUND:In the last decade, increasing evidence has shown that changes in human gut microbiota are associated with diseases, such as obesity. The excreted/secreted proteins (secretome) of the gut microbiota affect the microbial composition, altering its colonization and persistence. Furthermore, it influences microbiota-host interactions by triggering inflammatory reactions and modulating the host's immune response. The metatranscriptome is essential to elucidate which genes are expressed under diseases. In this regard, little is known about the expressed secretome in the microbiome. Here, we use a metatranscriptomic approach to delineate the secretome of the gut microbiome of Mexican children with normal weight (NW) obesity (O) and obesity with metabolic syndrome (OMS). Additionally, we performed the 16S rRNA profiling of the gut microbiota. RESULTS:Out of the 115,712 metatranscriptome genes that codified for proteins, 30,024 (26%) were predicted to be secreted, constituting the Secrebiome of the gut microbiome. The 16S profiling confirmed an increased abundance in Firmicutes and decreased in Bacteroidetes in the obesity groups, and a significantly higher richness and diversity than the normal weight group. We found novel biomarkers for obesity with metabolic syndrome such as increased Coriobacteraceae, Collinsela, and Collinsella aerofaciens; Erysipelotrichaceae, Catenibacterium and Catenibacterium sp., and decreased Parabacteroides distasonis, which correlated with clinical and anthropometric parameters associated to obesity and metabolic syndrome. Related to the Secrebiome, 16 genes, homologous to F. prausniitzi, were overexpressed for the obese and 15 genes homologous to Bacteroides, were overexpressed in the obesity with metabolic syndrome. Furthermore, a significant enrichment of CAZy enzymes was found in the Secrebiome. Additionally, significant differences in the antigenic density of the Secrebiome were found between normal weight and obesity groups. CONCLUSIONS:These findings show, for the first time, the role of the Secrebiome in the functional human-microbiota interaction. Our results highlight the importance of metatranscriptomics to provide novel information about the gut microbiome's functions that could help us understand the impact of the Secrebiome on the homeostasis of its human host. Furthermore, the metatranscriptome and 16S profiling confirmed the importance of treating obesity and obesity with metabolic syndrome as separate conditions to better understand the interplay between microbiome and disease.
Project description:Estrogens protect against diet-induced obesity in women and female rodents. For example, a lack of estrogens in postmenopausal women is associated with an increased risk of weight gain, cardiovascular diseases, low-grade inflammation, and cancer. Estrogens act with leptin to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. The gut microbiome is also critical in regulating metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) mice fed high-fat diet (HFD) that received either 17?-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes. Moreover, both obesity (ob/ob mice) and E2 were associated with reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared with vehicle mice. Regarding taxa, E2 was associated with an increased abundance of the S24-7 family, while leptin was associated with increases in Coriobacteriaceae, Clostridium and Lactobacillus. Some taxa were affected by both E2 and leptin, suggesting these hormones alter gut microbiota of HFD-fed female mice. Understanding the role of E2 and leptin in regulating gut microbiota will provide important insights into hormone-dependent metabolic disorders in women.
Project description:Obesity has been linked to the human gut microbiota; however, the contribution of gut bacterial species to the obese phenotype remains controversial because of conflicting results from studies in different populations. To explore the possible dysbiosis of gut microbiota in obesity and its metabolic complications, we studied men and women over a range of body mass indices from the Old Order Amish sect, a culturally homogeneous Caucasian population of Central European ancestry. We characterized the gut microbiota in 310 subjects by deep pyrosequencing of bar-coded PCR amplicons from the V1-V3 region of the 16S rRNA gene. Three communities of interacting bacteria were identified in the gut microbiota, analogous to previously identified gut enterotypes. Neither BMI nor any metabolic syndrome trait was associated with a particular gut community. Network analysis identified twenty-two bacterial species and four OTUs that were either positively or inversely correlated with metabolic syndrome traits, suggesting that certain members of the gut microbiota may play a role in these metabolic derangements.
Project description:Non-alcoholic fatty liver disease (NAFLD) is considered a worldwide healthcare problem that mirrors the increased prevalence of obesity. Gut microbiota plays a crucial role in the progression and treatment of NAFLD. Bofutsushosan (BTS), a pharmaceutical-grade Japanese traditional medicine, has long been prescribed in Japan for obesity and obesity-related syndrome. Although BTS has been reported to exert an anti-obesity effect in obese patients as well as various obesity-model animals, its effect on gut microbiota is unknown. Here, the effects of BTS on obesity, liver damage, and the gut microbiome in genetically obese mice, ob/ob, were studied. Seven-week-old ob/ob mice were fed a standard diet with (BTS group) or without (CONT group) 5% BTS for 4 weeks. By comparison to the CONT group, the BTS group showed reduced body weight gain and hyperlipidemia as well as improved liver function. Moreover, gut microbiota in the CONT and BTS group formed a significantly different cluster. Specifically, the genera Akkermansia, Bacteroides and an unknown genus of the family Enterobacteriaceae expanded dramatically in the BTS group. Noteworthy, the population of Akkermansia muciniphila, which is reported to elicit an anti-obesity effect and improve various metabolic abnormalities, was markedly increased (93-fold) compared with the CONT group. These results imply that BTS may be a promising agent for treating NAFLD.
Project description:Male Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and obesity-related metabolic syndrome. Gut dysbiosis, an imbalance of gut microbiota, has been implicated in the pathogenesis of metabolic syndrome, but its mechanisms are unknown. Short-chain fatty acids (SCFAs) are the main fermentation products of gut microbiota and a link between the gut microbiota and the host's physiology. Here, we investigated a correlation among gut dysbiosis, SCFAs, and metabolic syndrome in TSOD mice. We detected enriched levels of Gram-positive bacteria and corresponding decreases in Gram-negative bacteria in 24-wk-old metabolic syndrome-affected TSOD mice compared with age-matched controls. The abundance of Bacteroidetes species decreased, the abundance of Firmicutes species increased, and nine genera of bacteria were altered in 24-wk-old TSOD mice. The total plasma SCFA level was significantly lower in the TSOD mice than in controls. The major plasma SCFA-acetate-decreased in TSOD mice, whereas propionate and butyrate increased. TSOD mice had no minor SCFAs (valerate and hexanoate) but normal mice did. We thus concluded that gut dysbiosis and consequent disruptions in plasma SCFA profiles occurred in metabolic syndrome-affected TSOD mice. We also propose that the TSOD mouse is a useful model to study gut dysbiosis, SCFAs, and metabolic syndrome.
Project description:Changes in environmental and genetic factors are vital to development of obesity and its complications. Induction of obesity and type 2 diabetes by both leptin deficiency (ob/ob) and high fat diet (HFD) has been verified in animal models. In the present experiment, three types of diets (normal diet; ND, HFD and high sucrose diet; HSD) and two types of genetic mice (Wild type: WT and ob/ob) were used to explore the relationship among diet supplements, gut microbiota, host genetics and metabolic status. HFD increased the body, fat and liver weight of both ob/ob and WT mice, but HSD did not. HFD also resulted in dyslipidemia, as well as increased serum transaminases and fasting glucose in ob/ob mice but not in WT mice, while HSD did not. Moreover, HFD led to brain BDNF elevation in WT mice and reduction in ob/ob mice, whereas HSD did not. Both HFD and HSD had a greater influence on gut microbiota than host genotypes. In detail, both of HFD and HSD alteration elucidated the majority (?63%) of the whole structural variation in gut microbiota, however, host genetic mutation accounted for the minority (?11%). Overall, diets more intensively disturbed the structure of gut microbiota in excess of genetic change, particularly under leptin deficient conditions. Different responses of host genotypes may contribute to the development of metabolic disorder phenotypes linked with gut microbiota alterations.
Project description:OBJECTIVE:The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin. DESIGN:The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3?months. RESULTS:We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin. CONCLUSION:These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.
Project description:The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
Project description:Obesity is a metabolic disease characterized by low-grade inflammation and accompanied by dyslipidemia and up-regulation of other bioactive molecules, creating a predisposition to endothelial dysfunction and metabolic syndrome. We studied the association between gut microbiota diversity and endothelial dysfunction (EDF) markers in obese Mexican children and adolescents. We examined clinical data including metabolic factors and EDF markers in blood samples. Gut bacterial diversity was characterized by high-throughput sequencing of V3-16S rDNA libraries. Triglycerides, insulin, homeostasis model assessment-insulin resistant (HOMA-IR), leptin, C-reactive protein (CRP), and EDF marker intercellular adhesion molecule 1 (ICAM-1) were significantly higher in obese children and adolescents. Multivariate analysis showed statistically significant positive associations between vascular cell adhesion molecule 1 (VCAM-1) and Veillonellaceae, and between ICAM-1 and Ruminococcus in obese children. In obese adolescents, there was a statistically significant positive association between total cholesterol and Ruminococcus, and between ICAM-1 and Bacteroides. LEfSe analysis showed that the genus Lactobacillus and family Coriobacteriaceae were enriched in children, and genera Collinsella and Prevotella were enriched in obese adolescents. Obese children and adolescents had higher levels of insulin resistance and metabolic syndrome. These results suggest that obese Mexican children and adolescents had increased levels of CRP and a reduction of adiponectin, which causes higher expression of EDF markers, affecting endothelial function and associating with changes in the gut microbiota.
Project description:Polycystic ovary syndrome (PCOS) is a frequent endocrine and metabolic syndrome in reproductive-age women. Recently, emerging evidence has shown that gut microbiota is closely related to metabolic diseases such as type 2 diabetes, obesity and PCOS. In the present study, we established dihydrotestosterone (DHT)-induced PCOS rats and used Illumina MiSeq sequencing (PE300) to examine the composition, diversity, and abundance of the gut microbiota in PCOS. We compared the effects of three PCOS treatments: Diane-35 (estrogen and progesterone), probiotics and berberine. The DHT-induced rats showed constant estrous cycles, the loss of mature ovarian follicles, insulin resistance and obesity. The reproductive and metabolic functions in the PCOS rats were improved by treatment with Diane-35 and probiotics. Diane-35 and probiotics could restore the diversity of the gut microbiota, and the recovery of gut microbiota disorders improved the reproductive function in PCOS-like rats. However, berberine drastically reduced the species diversity and amount of gut microbiota and showed no improvement in PCOS. The findings of this study will help us to better understand the influence of the gut microbiota in the metabolic and reproductive alterations in PCOS as well as suggest opportunities for future personal dietary guidance for PCOS.