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      The Role of Probiotics and Prebiotics in the Prevention and Treatment of Obesity

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          Abstract

          Obesity is a global pandemic complex to treat due to its multifactorial pathogenesis—an unhealthy lifestyle, neuronal and hormonal mechanisms, and genetic and epigenetic factors are involved. Scientific evidence supports the idea that obesity and metabolic consequences are strongly related to changes in both the function and composition of gut microbiota, which exert an essential role in modulating energy metabolism. Modifications of gut microbiota composition have been associated with variations in body weight and body mass index. Lifestyle modifications remain as primary therapy for obesity and related metabolic disorders. New therapeutic strategies to treat/prevent obesity have been proposed, based on pre- and/or probiotic modulation of gut microbiota to mimic that found in healthy non-obese subjects. Based on human and animal studies, this review aimed to discuss mechanisms through which gut microbiota could act as a key modifier of obesity and related metabolic complications. Evidence from animal studies and human clinical trials suggesting potential beneficial effects of prebiotic and various probiotic strains on those physical, biochemical, and metabolic parameters related to obesity is presented. As a conclusion, a deeper knowledge about pre-/probiotic mechanisms of action, in combination with adequately powered, randomized controlled follow-up studies, will facilitate the clinical application and development of personalized healthcare strategies.

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          Most cited references127

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          Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice

          OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.
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            Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces.

            Weight loss diets for humans that are based on a high intake of protein but low intake of fermentable carbohydrate may alter microbial activity and bacterial populations in the large intestine and thus impact on gut health. In this study, 19 healthy, obese (body mass index range, 30 to 42) volunteers were given in succession three different diets: maintenance (M) for 3 days (399 g carbohydrate/day) and then high protein/medium (164 g/day) carbohydrate (HPMC) and high protein/low (24 g/day) carbohydrate (HPLC) each for 4 weeks. Stool samples were collected at the end of each dietary regimen. Total fecal short-chain fatty acids were 114 mM, 74 mM, and 56 mM (P < 0.001) for M, HPMC, and HPLC diets, respectively, and there was a disproportionate reduction in fecal butyrate (18 mM, 9 mM, and 4 mM, respectively; P < 0.001) with decreasing carbohydrate. Major groups of fecal bacteria were monitored using nine 16S rRNA-targeted fluorescence in situ hybridization probes, relative to counts obtained with the broad probe Eub338. No significant change was seen in the relative counts of the bacteroides (Bac303) (mean, 29.6%) or the clostridial cluster XIVa (Erec482, 23.3%), cluster IX (Prop853, 9.3%), or cluster IV (Fprau645, 11.6%; Rbro730 plus Rfla729, 9.3%) groups. In contrast, the Roseburia spp. and Eubacterium rectale subgroup of cluster XIVa (11%, 8%, and 3% for M, HPMC, and HPLC, respectively; P < 0.001) and bifidobacteria (4%, 2.1%, and 1.9%, respectively; P = 0.026) decreased as carbohydrate intake decreased. The abundance of butyrate-producing bacteria related to Roseburia spp. and E. rectale correlated well with the decline in fecal butyrate.
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              Effects of gut microbes on nutrient absorption and energy regulation.

              Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characterized by chronic low-level inflammation, such as obesity, through systemic exposure to bacterial lipopolysaccharide derived from the gut microbiota. In this review, the role of the gut microbiota in energy harvest and fat storage is explored, as well as differences in the microbiota in obesity and undernutrition.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                15 March 2019
                March 2019
                : 11
                : 3
                : 635
                Affiliations
                [1 ]Department of Pediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; tcr@ 123456ugr.es (T.C.); joseantonio_gsantos@ 123456outlook.es (J.A.G.-S.); mgbermudez@ 123456ugr.es (M.G.B.)
                [2 ]EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
                [3 ]Instituto de Investigación Biosanitaria ibs, GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
                [4 ]Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s node, Carlos III Health Institute of Health Carlos III, 28029 Madrid, Spain
                Author notes
                [* ]Correspondence: ccampoy@ 123456ugr.es ; Tel.: +34-629308695
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9860-6785
                Article
                nutrients-11-00635
                10.3390/nu11030635
                6470608
                30875987
                201f8f62-6712-4b50-8af6-b8b0105eb49b
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 February 2019
                : 11 March 2019
                Categories
                Review

                Nutrition & Dietetics
                obesity,gut microbiota,probiotics,prebiotics,nutrition
                Nutrition & Dietetics
                obesity, gut microbiota, probiotics, prebiotics, nutrition

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