Arlette Santacruz

Interplay Between Weight Loss and Gut Microbiota Composition in Overweight Adolescents

The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty‐six adolescents (13–15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie‐restricted diet (10–40%) and increased physical activity (15–23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real‐time PCR before and after the intervention. A group of subjects (n = 23) experienced >4.0 kg weight loss and showed significant BMI (P = 0.030) and BMI z‐score (P = 0.035) reductions after the intervention, while the other group (n = 13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P = 0.001) and Lactobacillus group (P = 0.030) counts, and to decreased Clostridium coccoides group (P = 0.028), Bifidobacterium longum (P = 0.031), and Bifidobacterium adolescentis (P = 0.044) counts. In the high weight–loss group, B. fragilis group and Lactobacillus group counts also increased (P = 0.001 and P = 0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P = 0.001 and P = 0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P < 0.001–0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P < 0.001–0.008) in the high weight–loss group than in the low weight–loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individuals microbiota.

Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents

Objective:To evaluate the effects of a multidisciplinary obesity treatment programme on fecal microbiota composition and immunoglobulin-coating bacteria in overweight and obese adolescents and their relationship to weight loss.Design:Longitudinal intervention study based on both a calorie-restricted diet (calorie reduction=10–40%) and increased physical activity (calorie expenditure=15–23 kcal/kg body weight per week) for 10 weeks.Participants:Thirty-nine overweight and obese adolescents (BMI mean 33.1 range 23.7–50.4; age mean 14.8 range, 13.0–16.0).Measurements:BMI, BMI z-scores and plasma biochemical parameters were measured before and after the intervention. Fecal microbiota was analyzed by fluorescent in situ hybridization. Immunoglobulin-coating bacteria were detected using fluorescent-labelled F(ab′)2 antihuman IgA, IgG and IgM.Results:Reductions in Clostridium histolyticum and E. rectale-C. coccoides proportions significantly correlated with weight and BMI z-score reductions in the whole adolescent population. Proportions of C. histolyticum, C. lituseburense and E. rectale-C. coccoides dropped significantly whereas those of the Bacteroides-Prevotella group increased after the intervention in those adolescents who lost more than 4 kg. Total fecal energy was almost significantly reduced in the same group of adolescents but not in the group that lost less than 2.5 kg. IgA-coating bacterial proportions also decreased significantly in participants who lost more than 6 kg after the intervention, paralleled to reductions in C. histolyticum and E. rectale-C. coccoides populations. E. rectale-C. coccoides proportions also correlated with weight loss and BMI z-score reduction in participants whose weight loss exceeded 4 kg.Conclusions:Specific gut bacteria and an associated IgA response were related to body weight changes in adolescents under lifestyle intervention. These results suggest interactions between diet, gut microbiota and host metabolism and immunity in obesity.

Gut microbiota in obesity and metabolic disorders

Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the hosts metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the hosts gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.

Microbiota and host determinants of behavioural phenotype in maternally separated mice

Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.

Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4-Induced Fibrosis

Background Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. Hypothesis and Aims We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. Animals and Methods Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, hosts specific butyrate-receptor GPR-43 and serum cytokine levels were measured. Results Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. Conclusions Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice.

High protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: The increased luminal bulk connection

High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem are poorly known. Here, rats were fed for 15 days with either a normoproteic diet (NP, 14% protein) or a hyperproteic-hypoglucidic isocaloric diet (HP, 53% protein). Cecum and colon were recovered for analysis. Short- and branched-chain fatty acids, as well as lactate, succinate, formate, and ethanol contents, were markedly increased in the colonic luminal contents of HP rats (P < 0.05 or less) but to a lower extent in the cecal luminal content. This was associated with reduced concentrations of the Clostridium coccoides and C. leptum groups and Faecalibacterium prausnitzii in both the cecum and colon (P < 0.05 or less). In addition, the microbiota diversity was found to be higher in the cecum of HP rats but was lower in the colon compared with NP rats. In HP rats, the colonic and cecal luminal content weights were markedly higher than in NP rats (P < 0.001), resulting in similar butyrate, acetate, and propionate concentrations. Accordingly, the expression of monocarboxylate transporter 1 and sodium monocarboxylate transporter 1 (which is increased by higher butyrate concentration) as well as the colonocyte capacity for butyrate oxidation were not modified by the HP diet, whereas the amount of butyrate in feces was increased (P < 0.01). It is concluded that an increased bulk in the large intestine content following HP diet consumption allows maintenance in the luminal butyrate concentration and thus its metabolism in colonocytes despite modified microbiota composition and increased substrate availability.

Insights into the Roles of Gut Microbes in Obesity

Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the hosts ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders.

Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis.

Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on bacterial translocation and the liver status in experimental cirrhosis.

Probiotics and Prebiotics in Metabolic Disorders and Obesity

Publisher Summary This chapter reviews the knowledge on the contribution of the gut microbiota to obesity and associated-metabolic disorders and the evidence on the possible benefits of interventions with probiotic, prebiotics, and synbiotics. Scientific evidence has demonstrated an association between the composition of the gut microbiota and body weight, which is under the influence of the diet and the lifestyle. The use of systems biology, together with metagenomic and metabolomic approaches, has also revealed a large number of roles possibly played by the gut microbiota in the metabolic and immune dysfunction associated with obesity. On this basis, the use of dietary strategies targeting the gut ecosystem has emerged as an additional tool to control metabolic disorders. So far only a few trials have demonstrated that the administration of probiotics, prebiotics, and their combination (synbiotics) exerts moderate positive effects in vivo . The findings indicate that advances in this field could be of value in improving the intervention strategies to treat and prevent obesity and its associated metabolic disorders. The future success of these strategies will entirely depend on a better understanding of the complex interactions taking place between the human genome, the microbiome, and the diet.

S1801 Neonatal Stress Induces Changes in the Enteric Nervous System and Gut Microflora

isothiocyanate (100 μM) induced transient contraction only. The reactivity was more pronounced to capsaicin than that to allyl-isothiocyanate in the rectum and distal colon. The non-selective NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 μM) or NG-nitro-L-arginine (L-NNA, 100 μM), which alone had no effect, markedly enhanced contractile responses to allyl-isothiocyanate in the distal colon, but did not in the rectum. Repeated applications of allyl-isothiocyanate in the presence of L-NAME or L-NNA did not produce such potentiation in contraction. The enhancement by L-NAME of allyl-isothiocyanate-induced contraction was inhibited by the pretreatment with the substrate of NO synthase, L-arginine (3 mM), but not D-arginine (3 mM). In addition, the neuronal NO synthase inhibitor Nω-propyl-L-arginine (0.2-200μM) significantly andmoderately potentiated transient contractile responses to allyl-isothiocyanate in the distal colon. However, the transient and long-lasting contraction in response to capsaicin was not affected by L-NAME in the rectum and distal colon. CONCLSION: These results suggest that endogenous NO derived from neuronal NO synthase modulates the smooth muscle contraction in response to TRPA1 activation in isolated mouse distal colon, but not the rectum, whereas contractile responses to the TRPV1 activation is not involved in endogenous NO in the mouse rectum and distal colon.