Search

Gut microbiota represents a therapeutic target for obesity. We hypothesize that B. uniformis CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior anti-obesity effects. We performed a 17-week intervention in diet-induced obese mice receiving either B. uniformis, WBE, or their combination to identify interactions and independent actions on metabolism and immunity. B. uniformis combined with WBE was the most effective intervention, curbing weight gain and adiposity, while exerting more modest effects separately. The combination restored insulin-dependent metabolic routes in fat and liver, although the bacterium was the primary driver for improving whole-body glucose disposal. Moreover, B. uniformis-combined with WBE caused the highest increases in butyrate and restored the proportion of induced intraepithelial lymphocytes and type-3 innate lymphoid cells in the intestinal epithelium. Thus, strengthening the first line of immune defense against unhealthy diets and associated dysbiosis in the intestine. This intervention also attenuated the altered IL22 signaling and liver inflammation. Our study shows opportunities for employing B. uniformis, combined with WBE, to aid in the treatment of obesity., This study was funded by the European Commission 7th Framework Programme through the MyNewGut project (Grant agreement No. 613979). The FPI scholarship from MCIU (Spain) to IL-A and the Erasmus+ (European commission) to CB-V are fully acknowledged.

Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. biformis to restore GLP-1 levels, enhancing GLP-1 neural signaling in the proximal and distal small intestine and GLP-1 sensitivity of vagal sensory neurons, and to modify the cecal abundance of unsaturated fatty acids and the bacterial species associated with metabolic health. Our findings overall suggest the potential use of H biformis in the management of type 2 diabetes in obesity to optimize the sensitivity and function of the GLP-1 system, through direct and indirect mechanisms., This study received funding from the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 797297 (M.R-P), from the European Union 7th Framework Program through the MyNewGut project (Grant agreement No. 613979) and from the Spanish Ministry of Science and Innovation (MICINN, Spain) (Grant AGL2017-88801-P). The FPI grant of I.L-A from the Ministry of Science and Innovation (MICINN; Spain) and the contract of C. B-V for promotion of youth employment in R+D+I from MICINN (Spain) are fully acknowledged.

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota–diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota–brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut–endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota–diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut–brain axis function and, thus, combat obesity., This work is supported by grant AGL2017-88801-P from the Spanish Ministry of Science and Innovation (MICINN, Spain). The Marie Sklodowska-Curie grant agreement No. 797297 (M.R-P), the FPI grant of I.L.-A., the FPU grant of R.L. and the Juan de la Cierva contract of M.O. and the contract of C. B-V for promotion of youth employment in R+D+I from MICINN (Spain) are fully acknowledged.

Obesity has reached epidemic proportions and is associated with chronic-low-grade inflammation and metabolic morbidities. Energy-dense diets and a sedentary lifestyle are determinants of obesity. The gut microbiome is a novel biological factor involved in obesity via interactions with the host and the diet. The gut microbiome act as a synergistic force protecting or aggravating the effects of the diet on the metabolic phenotype. The role of the microbiome in the regulation of intestinal and systemic immunity is one of the mechanisms by which it contributes to the host's response to the diet and to the pathophysiology of diet-induced obesity. Here, we review the mechanisms whereby “obesogenic” diets and the microbiome impact immunity, locally and systemically, focusing on the consequences in the gut–adipose tissue axis. We also review the structural and microbial metabolites that influence immunity and how advances in this field could help design microbiome-informed strategies to tackle obesity-related disorders more effectively., This study has been supported by the European Marie Skłodowska-Curie Action of H2020 MicroILCs (grant agreement: 890545) and the Spanish Ministry of Science and Innovation (MICINN) (grant AGL2017-88801-P). The FPU contract to R L-G from Spanish Ministry of Universities and the contract of Garantía Juvenil to CB-V from MICINN are fully acknowledged.