Portal de Periódicos da CAPES

Veggies and Intact Grains a Day Keep the Pathogens Away

2016; Cell Press; Volume: 167; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2016.10.047

1097-4172

Francesca S. Gazzaniga, Dennis L. Kasper,

Infant Nutrition and Health

In this issue of Cell, Desai et al. compare how dietary fiber affects the gut microbiota and susceptibility to disease. They find that a fiber-free diet promotes mucus-degrading bacteria and susceptibility to Citrobacter rodentium infection. In this issue of Cell, Desai et al. compare how dietary fiber affects the gut microbiota and susceptibility to disease. They find that a fiber-free diet promotes mucus-degrading bacteria and susceptibility to Citrobacter rodentium infection. The Western diet, characterized by increased fat and sugar intake and decreased fiber intake, has been implicated in a wide variety of diseases, including cancer, type 2 diabetes, and cardiovascular disease (Cordain et al., 2005Cordain L. Eaton S.B. Sebastian A. Mann N. Lindeberg S. Watkins B.A. O'Keefe J.H. Brand-Miller J. Am. J. Clin. Nutr. 2005; 81: 341-354Crossref PubMed Scopus (1605) Google Scholar). Furthermore, the Western diet is associated with changes in the bacteria in our gut—i.e., our gut microbiota (Turnbaugh et al., 2008Turnbaugh P.J. Bäckhed F. Fulton L. Gordon J.I. Cell Host Microbe. 2008; 3: 213-223Abstract Full Text Full Text PDF PubMed Scopus (2091) Google Scholar). These associations have led to the premise that diet influences the gut microbiota, which in turn influences health and disease. Generally, the Western diet is less diverse than more traditional diets (Turnbaugh et al., 2008Turnbaugh P.J. Bäckhed F. Fulton L. Gordon J.I. Cell Host Microbe. 2008; 3: 213-223Abstract Full Text Full Text PDF PubMed Scopus (2091) Google Scholar). Many researchers hope that, if we determine which of the bacteria necessary to promote a healthy gut are missing from our diet, we will be able to design a remedial probiotic (bacterial) or prebiotic (a supplement that feeds specific bacteria) or to change our diet to harness disease. To understand the mechanisms by which the Western diet influences the microbiota and disease, many studies of mice have focused on high-fat diets (Devkota et al., 2012Devkota S. Wang Y. Musch M.W. Leone V. Fehlner-Peach H. Nadimpalli A. Antonopoulos D.A. Jabri B. Chang E.B. Nature. 2012; 487: 104-108PubMed Google Scholar, Mahana et al., 2016Mahana D. Trent C.M. Kurtz Z.D. Bokulich N.A. Battaglia T. Chung J. Müller C.L. Li H. Bonneau R.A. Blaser M.J. Genome Med. 2016; 8: 48Crossref PubMed Scopus (115) Google Scholar, Turnbaugh et al., 2008Turnbaugh P.J. Bäckhed F. Fulton L. Gordon J.I. Cell Host Microbe. 2008; 3: 213-223Abstract Full Text Full Text PDF PubMed Scopus (2091) Google Scholar). It is commonly believed that increased fat intake is the cause for obesity-associated diseases, yet low-fat diets have failed to yield major health benefits (Taubes, 2001Taubes G. Science. 2001; 291: 2536-2545Crossref PubMed Scopus (123) Google Scholar). Instead, other aspects of the Western diet may be responsible for gut microbiota changes and disease. In fact, recent studies show that dietary fiber promotes the growth of symbiotic bacteria that increase the production of short-chain fatty acids and protect the host from a variety of diseases (Sonnenburg and Sonnenburg, 2014Sonnenburg E.D. Sonnenburg J.L. Cell Metab. 2014; 20: 779-786Abstract Full Text Full Text PDF PubMed Scopus (429) Google Scholar). Little is known, however, about the mechanisms by which reduced fiber influences the microbiota and disease. In a study in this issue of Cell, Desai et al., 2016Desai M.S. Seekatz A.M. Koropatkin N.M. Kamada N. Hickey C.A. Wolter M. Pudlo N.A. Kitamoto S. Terrapon N. Muller A. et al.Cell. 2016; 167 (this issue): 1339-1353Abstract Full Text Full Text PDF PubMed Scopus (1301) Google Scholar designed a synthetic microbiota (SM) to investigate how dietary fiber affects the composition of the gut microbiota and protection from disease. This SM is composed of 14 commensal species that represent the five dominant bacterial phyla present in a human gut. To characterize the metabolic properties of each of these species, the authors evaluated its growth in vitro with 42 different plant- and animal-derived mono- and polysaccharides. Germ-free (GF) mice colonized with the SM were fed fiber-rich (FR; 15% fiber from minimally processed grains and plants), fiber-free (FF), and prebiotic (Pre; purified soluble glycans found in prebiotics) diets. To imitate the fluctuating human diet, some groups of mice were alternately fed FR and FF or Pre and FF diets, switching every other day or every 4 days. The numbers of two mucus-degrading bacterial species—Akkermansia muciniphila and Bacteroides caccae—increased on the FF diet, whereas the growth of two fiber-metabolizing species—Bacteroides ovatus and Eubacterium rectale—decreased. These changes also occurred when mice were fed alternating diets. The Pre diet affected the microbial community in a manner similar to the FF diet; this observation suggests that eating foods containing prebiotics does not have the same beneficial effect as actually eating dietary fiber. Transcription analysis of the bacteria confirmed these findings, showing an increase in fiber-metabolizing enzymes on the FR diet and in mucus-degrading enzymes on the FF diet (Desai et al., 2016Desai M.S. Seekatz A.M. Koropatkin N.M. Kamada N. Hickey C.A. Wolter M. Pudlo N.A. Kitamoto S. Terrapon N. Muller A. et al.Cell. 2016; 167 (this issue): 1339-1353Abstract Full Text Full Text PDF PubMed Scopus (1301) Google Scholar). Further analysis of the intestines of these mice showed a thicker mucus layer in FR mice than in FF mice. This difference suggests that, in the absence of dietary fiber, mucus-degrading bacteria outcompete fiber-metabolizing bacteria by degrading the host mucus lining. The mice on the alternating FR and FF diets had a mucus layer of intermediate thickness (Desai et al., 2016Desai M.S. Seekatz A.M. Koropatkin N.M. Kamada N. Hickey C.A. Wolter M. Pudlo N.A. Kitamoto S. Terrapon N. Muller A. et al.Cell. 2016; 167 (this issue): 1339-1353Abstract Full Text Full Text PDF PubMed Scopus (1301) Google Scholar). To investigate whether the FF diet had any negative health effects, GF and SM mice fed FR or FF diets were challenged with the mouse pathogen Citrobacter rodentium. SM mice fed the FF diet became much sicker than mice fed the FR diet. GF mice on either diet did not display disease symptoms, a result suggesting that a synergistic effect between the thin mucus layer and mucus-degrading bacteria promotes C. rodentium disease (Figure 1). These data suggest that an FF diet promotes outgrowth of mucus-degrading bacteria, which in conjunction with a thinner mucus wall, increases susceptibility to the pathogen. Using a synthetic, well-characterized microbiota, this paper tracks how dietary fiber influences gut bacterial composition and how the bacteria studied affect gut health. Even though GF mice were gavaged with the same set of bacteria, dietary fiber influenced the ratio of these bacteria in the gut. These results help explain why, although gut bacteria have been shown to play a major role in health and disease, studies of supplemental probiotics have found an underwhelming impact. The present study suggests that, if probiotics are given but the host's diet does not promote their growth, other bacteria will outcompete them and any health benefits will be lost. In addition, this investigation shows that current prebiotics fail to exert the same effects as a fiber-rich diet. Future studies exploring how to prevent the growth of mucus-degrading bacteria, determining which prebiotics can promote the growth of beneficial bacteria, and identifying which combinations of bacteria are ideal for host health are on the horizon. In the meantime, it looks as if we should eat our vegetables … at least every other day. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen SusceptibilityDesai et al.CellNovember 17, 2016In BriefRegular consumption of dietary fiber helps prevent erosion of the intestinal mucus barrier by the gut microbiome, blunting pathogen infection and reducing the incidence of colitis. Full-Text PDF Open Archive