NATURE REVIEWS | ENDOCRINOLOGY VOLUME 7 | NOVEMBER 2011 | 639 Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, 73 Avenue Emmanuel Mounier, Box B1.73.11, B‑1200 Brussels, Belgium (N. M. Delzenne, A. M. Neyrinck, P. D. Cani). Sahlgrenska Centre for Cardiovascular and Metabolic Research, Wallenberg Laboratory Department of Molecular and Clinical Medicine, University of Gothenburg, Bruna Stråket 16, SE‑41345 Gothenburg, Sweden (F. Bäckhed). Correspondence to: N. M. Delzenne nathalie.delzenne@ uclouvain.be Targeting gut microbiota in obesity: effects of prebiotics and probiotics Nathalie M. Delzenne, Audrey M. Neyrinck, Fredrik Bäckhed and Patrice D. Cani Abstract | At birth, the human colon is rapidly colonized by gut microbes. Owing to their vast number and their capacity to ferment nutrients and secrete bioactive compounds, these gastrointestinal microbes act as an environmental factor that affects the host’s physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. Experiments that compared germ‑free and colonized mice or analyzed the influence of nutrients that qualitatively change the composition of the gut microbiota (namely prebiotics) showed that gut microbes induce a wide variety of host responses within the intestinal mucosa and thereby control the gut’s barrier and endocrine functions. Gut microbes also influence the metabolism of cells in tissues outside of the intestines (in the liver and adipose tissue) and thereby modulate lipid and glucose homeostasis, as well as systemic inflammation, in the host. A number of studies describe characteristic differences between the composition and/or activity of the gut microbiota of lean individuals and those with obesity. Although these data are controversial, they suggest that specific phyla, classes or species of bacteria, or bacterial metabolic activities could be beneficial or detrimental to patients with obesity. The gut microbiota is, therefore, a potential nutritional and pharmacological target in the management of obesity and obesity‑related disorders. Delzenne, N. M. et al. Nat. Rev. Endocrinol. 7, 639–646 (2011); published online 9 August 2011; doi:10.1038/nrendo.2011.126 Introduction The human gut is home to 10 14 bacteria, which out- number the total of eukaryotic cells in the human body by an order of magnitude. At birth, the gut of a neonate is sterile. However, at birth, it is immediately colonized by maternal and environmental bacteria, and the com- plexity of the resulting gut microbiota increases until the weaning to solid foods. 1 The adult microbiota harbors 1,000–1,150 bacterial species, and some experts have suggested that 160 of these species constitute the core microbiota that is present in most individuals. 2 Although many of these species are found in the majority of people, their relative abundance can vary greatly. 3,4 By con- trast, studies of microbial coding sequences (called the metagenome) have made it increasingly clear that the functions encoded by the metagenome exhibit great similarity between individuals. 4 The human and mouse gut is dominated by several bacterial phyla including Bacteroidetes, Firmicutes and Actinobacteria. Some studies have indicated that an altered gut micro- biota is associated with several diseases that are particu- larly prevalent in the 21 st century. For example, reduced microbial diversity—a sign of a dysfunctional ecosystem that leads to a decreased stability of the microbiota —has been associated with both inflammatory bowel disease and obesity. 2,4,5 The first studies on the relation- ship between the composition of the gut microbiota and obesity have shown that the number of Firmicutes was increased whereas the number of Bacteroidetes was reduced in obese mice and humans compared with lean individuals. 6–9 Interestingly, weight loss achieved by dieting was able to reverse those changes. Although the decrease in the number of Bacteroidetes was not observed in all studies, 10,11 changes in this phylum have been sug- gested to result from an increased energy intake rather than being caused directly by obesity. 9 The bacterial changes at the taxonomic level in individuals with obesity have been described elsewhere. 12,13 In the first part of this Review, we describe the major factors that could modulate gut microbiota composition, including genetic background, sex, age and diet of the host. In the second part, we describe how gut microbes change the energy metabolism of the host by altering the expres- sion of genes involved in the development of adiposity and obesity-related metabolic disorders, including inflamma- tion. The last part of the Review focuses on the potential role of specific nutrients that target the gut microbiota in the control of obesity and its comorbidities. Selecting host-adapted gut microbiota Various components influence the microbial ecology of the gut (Figure 1). In an elegant study, Rawls and coworkers demonstrated that the host can select an opti- mal microbiota. 14 When germ-free zebrafish were colo- nized with anaerobic mouse gut microbiota and germ-free mice were colonized with aerobic zebrafish microbiota, the host microbiota reshaped the transplanted microbiota within 2 weeks in both cases. 14 Obviously, physiological characteristics and habitats of fish and mice are very dif- ferent. However, this observation suggests that the host Competing interests The authors declare no competing interests. REVIEWS © 2011 Macmillan Publishers Limited. All rights reserved