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- W2924130156 abstract "•Mice are colonized with ten bacterial strains to create a simple human microbiota model•Dietary changes alter colonization patterns of the simplified intestinal microbiota (SIM)•SIM-diet interactions affect some circulating metabolites in the host•The SIM affects host metabolism in a diet-specific manner The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases. The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases. The human gut is populated with a dense and complex community of microbes, collectively known as the gut microbiota (Dethlefsen et al., 2007Dethlefsen L. McFall-Ngai M. Relman D.A. An ecological and evolutionary perspective on human-microbe mutualism and disease.Nature. 2007; 449: 811-818Crossref PubMed Scopus (1128) Google Scholar). The dominating phyla in the human gut are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia, but other phyla, such as Fusobacteria, Cyanobacteria, Lentisphaerae, Spirochaetes, and TM7, are also present (Arumugam et al., 2011Arumugam M. Raes J. Pelletier E. Le Paslier D. Yamada T. Mende D.R. Fernandes G.R. Tap J. Bruls T. Batto J.-M. et al.MetaHIT ConsortiumEnterotypes of the human gut microbiome.Nature. 2011; 473: 174-180Crossref PubMed Scopus (4428) Google Scholar, Qin et al., 2010Qin J. Li R. Raes J. Arumugam M. Burgdorf K.S. Manichanh C. Nielsen T. Pons N. Levenez F. Yamada T. et al.MetaHIT ConsortiumA human gut microbial gene catalogue established by metagenomic sequencing.Nature. 2010; 464: 59-65Crossref PubMed Scopus (7273) Google Scholar). The gut microbiota is associated with many essential functions for host physiology (Sommer and Bäckhed, 2013Sommer F. Bäckhed F. The gut microbiota—masters of host development and physiology.Nat. Rev. Microbiol. 2013; 11: 227-238Crossref PubMed Scopus (2086) Google Scholar). For example, a key function of microbes in the gut is to process complex carbohydrates that cannot be digested by host enzymes (Sonnenburg and Bäckhed, 2016Sonnenburg J.L. Bäckhed F. Diet-microbiota interactions as moderators of human metabolism.Nature. 2016; 535: 56-64Crossref PubMed Scopus (1196) Google Scholar) into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, and organic acids such as succinate and lactate (Cummings and Macfarlane, 1991Cummings J.H. Macfarlane G.T. The control and consequences of bacterial fermentation in the human colon.J. Appl. Bacteriol. 1991; 70: 443-459Crossref PubMed Scopus (1121) Google Scholar, Koh et al., 2016Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell. 2016; 165: 1332-1345Abstract Full Text Full Text PDF PubMed Scopus (2731) Google Scholar, Macfarlane and Macfarlane, 2012Macfarlane G.T. Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health.J. AOAC Int. 2012; 95: 50-60Crossref PubMed Scopus (614) Google Scholar). These metabolites are not only essential for the growth and cellular function of certain microbes in the gut (Cummings and Macfarlane, 1991Cummings J.H. Macfarlane G.T. The control and consequences of bacterial fermentation in the human colon.J. Appl. Bacteriol. 1991; 70: 443-459Crossref PubMed Scopus (1121) Google Scholar, Fischbach and Sonnenburg, 2011Fischbach M.A. Sonnenburg J.L. Eating for two: how metabolism establishes interspecies interactions in the gut.Cell Host Microbe. 2011; 10: 336-347Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar, Koh et al., 2016Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell. 2016; 165: 1332-1345Abstract Full Text Full Text PDF PubMed Scopus (2731) Google Scholar) but also affect host physiology (Koh et al., 2016Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell. 2016; 165: 1332-1345Abstract Full Text Full Text PDF PubMed Scopus (2731) Google Scholar, Zhao et al., 2018Zhao L. Zhang F. Ding X. Wu G. Lam Y.Y. Wang X. Fu H. Xue X. Lu C. Ma J. et al.Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.Science. 2018; 359: 1151-1156Crossref PubMed Scopus (1095) Google Scholar). Although the production of SCFAs resulting from the bacterial fermentation of fiber-rich diets is generally associated with beneficial metabolic effects, the increased energy harvest has also been proposed to contribute to diet-induced obesity in mice (Koh et al., 2016Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell. 2016; 165: 1332-1345Abstract Full Text Full Text PDF PubMed Scopus (2731) Google Scholar). Furthermore, the gut microbiota produces other metabolites that are influenced by the diet, many of which are likely to play a role in host physiology (Koh et al., 2016Koh A. De Vadder F. Kovatcheva-Datchary P. Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.Cell. 2016; 165: 1332-1345Abstract Full Text Full Text PDF PubMed Scopus (2731) Google Scholar, Makki et al., 2018Makki K. Deehan E.C. Walter J. Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease.Cell Host Microbe. 2018; 23: 705-715Abstract Full Text Full Text PDF PubMed Scopus (986) Google Scholar, Zmora et al., 2019Zmora N. Suez J. Elinav E. You are what you eat: diet, health and the gut microbiota.Nat. Rev. Gastroenterol. Hepatol. 2019; 16: 35-56Crossref PubMed Scopus (646) Google Scholar). Studies to delineate the interactions between gut bacteria, diet, and host metabolism are challenging because (1) of the complexity and high inter-individual variability of human gut microbiota, (2) bacteria interact in complex food webs in concert with the host, and (3) the microbiota consists mainly of non-sequenced members, thus limiting interpretation from metagenomic and metatranscriptomic analyses. One approach to overcome these issues is to use gnotobiotic animals colonized with a simplified intestinal microbial community consisting of well-characterized bacteria from humans. A recent example of such a model used rats colonized with eight bacterial species from the human gut to investigate how the microbiota composition changes in response to dietary challenges (Becker et al., 2011Becker N. Kunath J. Loh G. Blaut M. Human intestinal microbiota: characterization of a simplified and stable gnotobiotic rat model.Gut Microbes. 2011; 2: 25-33Crossref PubMed Scopus (112) Google Scholar). Others have used mice colonized with a defined community of human bacteria to investigate microbe-microbe interactions (McNulty et al., 2013McNulty N.P. Wu M. Erickson A.R. Pan C. Erickson B.K. Martens E.C. Pudlo N.A. Muegge B.D. Henrissat B. Hettich R.L. Gordon J.I. Effects of diet on resource utilization by a model human gut microbiota containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome.PLoS Biol. 2013; 11: e1001637Crossref PubMed Scopus (191) Google Scholar, Rey et al., 2013Rey F.E. Gonzalez M.D. Cheng J. Wu M. Ahern P.P. Gordon J.I. Metabolic niche of a prominent sulfate-reducing human gut bacterium.Proc. Natl. Acad. Sci. U S A. 2013; 110: 13582-13587Crossref PubMed Scopus (240) Google Scholar) or the interactions between microbiota, dietary fiber, and the colonic mucus barrier (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.A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility.Cell. 2016; 167: 1339-1353.e21Abstract Full Text Full Text PDF PubMed Scopus (1301) Google Scholar). However, none of these studies investigated how diet-induced changes in the gut microbiota affect host metabolism in parallel with altered microbial gene expression. To investigate the effect of microbiota-diet interactions on host metabolism, we developed a gnotobiotic mouse model colonized with ten representatives of the human intestinal microbiota (simplified intestinal microbiota [SIM]). Our selection was based on the following criteria: (1) All members of the dominant phyla in the human gut should be represented. (2) The chosen strains must have been sequenced, thus allowing us to characterize how specific nutrients (fiber, saturated fat, and sucrose) affect the microbial gene expression. (3) The chosen strains must have well-characterized metabolic functions (to digest and/or ferment carbohydrates) and trophic interactions with a range of cross-feeding interactions for dietary conversions in the gut. The main metabolic function and metabolites produced by each SIM bacterial strain in in vitro studies are presented in Table 1. Because H2 is produced during fermentation and accumulation of H2 decreases the metabolic activity of microbes (Rey et al., 2013Rey F.E. Gonzalez M.D. Cheng J. Wu M. Ahern P.P. Gordon J.I. Metabolic niche of a prominent sulfate-reducing human gut bacterium.Proc. Natl. Acad. Sci. U S A. 2013; 110: 13582-13587Crossref PubMed Scopus (240) Google Scholar), we also included the H2-consuming sulfate-reducing bacterium Desulfovibrio piger.Table 1Phylogenetic and Metabolic Features of the Members of the SIMSIM BacteriumPhylumMetabolic FunctionProduced MetabolitesReferencesAkkermansia muciniphila: DSM 22959Verrucomicrobiamucin degradationacetate, propionateDerrien et al., 2004Derrien M. Vaughan E.E. Plugge C.M. de Vos W.M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium.Int. J. Syst. Evol. Microbiol. 2004; 54: 1469-1476Crossref PubMed Scopus (1185) Google ScholarBacteroides thetaiotaomicron: ATCC 29148Bacteroidetespolysaccharide breakdown; mucinacetate, propionate, succinateMartens et al., 2008Martens E.C. Chiang H.C. Gordon J.I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.Cell Host Microbe. 2008; 4: 447-457Abstract Full Text Full Text PDF PubMed Scopus (553) Google Scholar, Xu et al., 2003Xu J. Bjursell M.K. Himrod J. Deng S. Carmichael L.K. Chiang H.C. Hooper L.V. Gordon J.I. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis.Science. 2003; 299: 2074-2076Crossref PubMed Scopus (1027) Google ScholarBifidobacterium adolescentis: L2-32Actinobacteriadi- and oligosaccharide breakdownacetate, lactateDuranti et al., 2016Duranti S. Milani C. Lugli G.A. Mancabelli L. Turroni F. Ferrario C. Mangifesta M. Viappiani A. Sánchez B. Margolles A. et al.Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis.Sci. Rep. 2016; 6: 23971Crossref PubMed Scopus (75) Google Scholar, Marquet et al., 2009Marquet P. Duncan S.H. Chassard C. Bernalier-Donadille A. Flint H.J. Lactate has the potential to promote hydrogen sulphide formation in the human colon.FEMS Microbiol. Lett. 2009; 299: 128-134Crossref PubMed Scopus (86) Google Scholar, Pokusaeva et al., 2011Pokusaeva K. Fitzgerald G.F. van Sinderen D. Carbohydrate metabolism in Bifidobacteria.Genes Nutr. 2011; 6: 285-306Crossref PubMed Scopus (475) Google ScholarCollinsella aerofaciens: DSM 3979Actinobacteriadi- and oligosaccharide breakdownacetate, lactate, formate, H2Flint et al., 2012Flint H.J. Scott K.P. Duncan S.H. Louis P. Forano E. Microbial degradation of complex carbohydrates in the gut.Gut Microbes. 2012; 3: 289-306Crossref PubMed Scopus (1144) Google Scholar, Kageyama and Benno, 2000Kageyama A. Benno Y. Emendation of genus Collinsella and proposal of Collinsella stercoris sp. nov. and Collinsella intestinalis sp. nov.Int. J. Syst. Evol. Microbiol. 2000; 50: 1767-1774Crossref PubMed Scopus (26) Google ScholarDesulfovibrio piger: DSM 749Proteobacteriasulfate reducer, lactate useracetate, H2SMarquet et al., 2009Marquet P. Duncan S.H. Chassard C. Bernalier-Donadille A. Flint H.J. Lactate has the potential to promote hydrogen sulphide formation in the human colon.FEMS Microbiol. Lett. 2009; 299: 128-134Crossref PubMed Scopus (86) Google ScholarEubacterium hallii: L2-7Firmicutesdi- and monosaccharide breakdown; lactate userbutyrateDuncan et al., 2004bDuncan S.H. Louis P. Flint H.J. Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product.Appl. Environ. Microbiol. 2004; 70: 5810-5817Crossref PubMed Scopus (709) Google Scholar, Scott et al., 2014Scott K.P. Martin J.C. Duncan S.H. Flint H.J. Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro.FEMS Microbiol. Ecol. 2014; 87: 30-40Crossref PubMed Scopus (278) Google ScholarEubacterium rectale: A1-86Firmicutesoligosaccharide breakdown; acetate userbutyrate, lactate, formate, H2Duncan and Flint, 2008Duncan S.H. Flint H.J. Proposal of a neotype strain (A1-86) for Eubacterium rectale. Request for an opinion.Int. J. Syst. Evol. Microbiol. 2008; 58: 1735-1736Crossref PubMed Scopus (45) Google Scholar, Duncan et al., 2008Duncan S.H. Lobley G.E. Holtrop G. Ince J. Johnstone A.M. Louis P. Flint H.J. Human colonic microbiota associated with diet, obesity and weight loss.Int. J. Obes. 2008; 32: 1720-1724Crossref PubMed Scopus (882) Google ScholarPrevotella copri: DSM 18205Bacteroidetespolysaccharide breakdownsuccinate, H2Flint et al., 2012Flint H.J. Scott K.P. Duncan S.H. Louis P. Forano E. Microbial degradation of complex carbohydrates in the gut.Gut Microbes. 2012; 3: 289-306Crossref PubMed Scopus (1144) Google Scholar, Hayashi et al., 2007Hayashi H. Shibata K. Sakamoto M. Tomita S. Benno Y. Prevotella copri sp. nov. and Prevotella stercorea sp. nov., isolated from human faeces.Int. J. Syst. Evol. Microbiol. 2007; 57: 941-946Crossref PubMed Scopus (111) Google Scholar, Kovatcheva-Datchary et al., 2015Kovatcheva-Datchary P. Nilsson A. Akrami R. Lee Y.S. De Vadder F. Arora T. Hallen A. Martens E. Björck I. Bäckhed F. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella.Cell Metab. 2015; 22: 971-982Abstract Full Text Full Text PDF PubMed Scopus (861) Google ScholarRoseburia inulinivorans: A2-194Firmicutesoligosaccharide breakdownbutyrate, propionateDuncan et al., 2006Duncan S.H. Aminov R.I. Scott K.P. Louis P. Stanton T.B. Flint H.J. Proposal of Roseburia faecis sp. nov., Roseburia hominis sp. nov. and Roseburia inulinivorans sp. nov., based on isolates from human faeces.Int. J. Syst. Evol. Microbiol. 2006; 56: 2437-2441Crossref PubMed Scopus (137) Google Scholar, Scott et al., 2006Scott K.P. Martin J.C. Campbell G. Mayer C.-D. Flint H.J. Whole-genome transcription profiling reveals genes up-regulated by growth on fucose in the human gut bacterium “Roseburia inulinivorans”.J. Bacteriol. 2006; 188: 4340-4349Crossref PubMed Scopus (171) Google ScholarRuminococcus bromii: L2-63Firmicutespolysaccharide breakdownacetate, formate, H2Crost et al., 2018Crost E.H. Le Gall G. Laverde-Gomez J.A. Mukhopadhya I. Flint H.J. Juge N. Mechanistic insights into the cross-feeding of Ruminococcus gnavus and Ruminococcus bromii on host and dietary carbohydrates.Front. Microbiol. 2018; 9: 2558Crossref PubMed Scopus (80) Google Scholar, Ze et al., 2012Ze X. Duncan S.H. Louis P. Flint H.J. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon.ISME J. 2012; 6: 1535-1543Crossref PubMed Scopus (576) Google Scholar Open table in a new tab We introduced the ten selected bacteria (Table 1) into germ-free (GF) Swiss Webster mice and maintained them for four generations to generate stably colonized SIM mice. We showed that all ten bacteria of the SIM community colonized each region of the gut of SIM mice on a chow diet, although Eubacterium hallii was present only at a low density throughout (Figure 1A). Levels of SIM bacteria were higher in the distal part of the gut compared with the small intestine, with the highest levels in the feces of SIM mice (Figure 1A), consistent with the fact that the SIM bacteria were chosen because of their importance for carbohydrate fermentation. A previous metagenome analysis has shown that all of the SIM bacteria, with the exception of Roseburia inulinivorans, are frequent colonizers of the human gut (Qin et al., 2010Qin J. Li R. Raes J. Arumugam M. Burgdorf K.S. Manichanh C. Nielsen T. Pons N. Levenez F. Yamada T. et al.MetaHIT ConsortiumA human gut microbial gene catalogue established by metagenomic sequencing.Nature. 2010; 464: 59-65Crossref PubMed Scopus (7273) Google Scholar). We confirmed that the ten taxa of the SIM community were present in feces from two healthy human donors (Figures 1B and 1C). For comparison with SIM mice, we then colonized GF mice with unfractionated microbiota from each of the two human donors for 2 weeks. We showed that all ten SIM bacteria were present in the cecum of chow-fed mice colonized with feces from one of these donors (Figure 1B) and all except Collinsella aerofaciens were present in the cecum of chow-fed mice colonized with microbiota from the second donor (Figure 1C). This unsuccessful colonization of C. aerofaciens may be explained by the fact that the second donor had low fecal levels of C. aerofaciens and that this species must compete with other members of the human microbiota beyond the ten present in the SIM community. However, the overall profiles of the ten SIM bacteria were similar in the SIM mice and the humanized mice on a chow diet, indicating that the SIM community may be a suitable simplified model of the human gut microbiota. A major selection criterion of the SIM bacteria was their capacity to metabolize carbohydrates and participate in anaerobic food webs in the gut. We therefore assessed how the abundance of SIM members was affected by changing the mouse diet from chow, which is low in fat (9% by weight) and high in dietary fiber (i.e., plant polysaccharides; 15% by weight), to one of two purified diets with low dietary fiber (primarily cellulose) but different macronutrient compositions. One group of SIM mice received a “Western” high-fat/high-sucrose (HF-HS) diet (fat 20% by weight, sucrose 18% by weight) for 2 weeks; a second group received a zero-fat/high-sucrose (ZF-HS) diet (sucrose 63% by weight) for 2 weeks (Table S1); a third group remained on chow. The total bacterial load in the cecum of SIM mice was not affected by a change in the diet (Figure 2A). However, compared with SIM mice that remained on chow, SIM mice that switched to a diet low in dietary fiber had reduced cecal abundance of Prevotella copri and Bifidobacterium adolescentis (with either HF-HS or ZF-HS diet), Ruminococcus bromii (with HF-HS diet), and R. inulinivorans (with ZF-HS diet) as well as a trend toward reduced abundance of C. aerofaciens (with ZF-HS diet; p = 0.052) (Figure 2A). Thus, a reduction in dietary fiber reduced the abundance of these fiber-degrading bacteria. These results are consistent with earlier studies showing that P. copri, B. adolescentis, R. inulinivorans, R. bromii, and C. aerofaciens have increased abundance when the diet is rich in complex plant polysaccharides (Kovatcheva-Datchary et al., 2015Kovatcheva-Datchary P. Nilsson A. Akrami R. Lee Y.S. De Vadder F. Arora T. Hallen A. Martens E. Björck I. Bäckhed F. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella.Cell Metab. 2015; 22: 971-982Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, Ramirez-Farias et al., 2009Ramirez-Farias C. Slezak K. Fuller Z. Duncan A. Holtrop G. Louis P. Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii.Br. J. Nutr. 2009; 101: 541-550Crossref PubMed Scopus (36) Google Scholar, Scott et al., 2014Scott K.P. Martin J.C. Duncan S.H. Flint H.J. Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro.FEMS Microbiol. Ecol. 2014; 87: 30-40Crossref PubMed Scopus (278) Google Scholar, Walker et al., 2011Walker A.W. Ince J. Duncan S.H. Webster L.M. Holtrop G. Ze X. Brown D. Stares M.D. Scott P. Bergerat A. et al.Dominant and diet-responsive groups of bacteria within the human colonic microbiota.ISME J. 2011; 5: 220-230Crossref PubMed Scopus (1112) Google Scholar, Vital et al., 2018Vital M. Howe A. Bergeron N. Krauss R.M. Jansson J.K. Tiedje J.M. Metagenomic insights into resistant starch degradation by human gut microbiota.Appl. Environ. Microbiol. 2018; 84 (e01562-18)Crossref PubMed Scopus (53) Google Scholar). Furthermore, a recent study reported that bacteria from the phylogenetic order Bacteroidales (to which Prevotella species belong) are lost in mice after several generations of feeding with a Western diet (Sonnenburg et al., 2016Sonnenburg E.D. Smits S.A. Tikhonov M. Higginbottom S.K. Wingreen N.S. Sonnenburg J.L. Diet-induced extinctions in the gut microbiota compound over generations.Nature. 2016; 529: 212-215Crossref PubMed Scopus (946) Google Scholar). Similarly, a loss of Prevotella strains has been reported in the gut microbiome of non-Western individuals after immigration to a Western country (Vangay et al., 2018Vangay P. Johnson A.J. Ward T.L. Al-Ghalith G.A. Shields-Cutler R.R. Hillmann B.M. Lucas S.K. Beura L.K. Thompson E.A. Till L.M. et al.US immigration westernizes the human gut microbiome.Cell. 2018; 175: 962-972.e10Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar). In addition, two recent studies in humans showed that short-term dietary changes to reduce complex carbohydrates resulted in rapid reductions in abundance of Bifidobacterium, Ruminococcus, and Roseburia, bacteria that metabolize complex carbohydrates in the gut (David et al., 2014David L.A. Maurice C.F. Carmody R.N. Gootenberg D.B. Button J.E. Wolfe B.E. Ling A.V. Devlin A.S. Varma Y. Fischbach M.A. et al.Diet rapidly and reproducibly alters the human gut microbiome.Nature. 2014; 505: 559-563Crossref PubMed Scopus (5570) Google Scholar, Mardinoglu et al., 2018Mardinoglu A. Wu H. Björnson E. Zhang C. Hakkarainen A. Räsänen S.M. Lee S. Mancina R.M. Bergentall M. Pietiläinen K.H. et al.An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans.Cell Metab. 2018; 27: 559-571.e5Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar). The cecal abundance of E. hallii was higher in SIM mice that switched from chow to an HF-HS or a ZF-HS diet (Figure 2A). In agreement, a dietary intervention study in humans showed that resistant starch (a prominent dietary fiber) reduced the abundance of E. hallii (Salonen et al., 2014Salonen A. Lahti L. Salojärvi J. Holtrop G. Korpela K. Duncan S.H. Date P. Farquharson F. Johnstone A.M. Lobley G.E. et al.Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men.ISME J. 2014; 8: 2218-2230Crossref PubMed Scopus (391) Google Scholar). Furthermore, in vitro studies have shown that E. hallii can use a broad range of substrates, including glucose, lactose, galactose, glycerol, and amino sugars (Bunesova et al., 2018Bunesova V. Lacroix C. Schwab C. Mucin cross-feeding of infant Bifidobacteria and Eubacterium hallii.Microb. Ecol. 2018; 75: 228-238Crossref PubMed Scopus (75) Google Scholar, Duncan et al., 2004aDuncan S.H. Holtrop G. Lobley G.E. Calder A.G. Stewart C.S. Flint H.J. Contribution of acetate to butyrate formation by human faecal bacteria.Br. J. Nutr. 2004; 91: 915-923Crossref PubMed Scopus (294) Google Scholar, Engels et al., 2016Engels C. Ruscheweyh H.-J. Beerenwinkel N. Lacroix C. Schwab C. The common gut microbe Eubacterium hallii also contributes to intestinal propionate formation.Front. Microbiol. 2016; 7: 713Crossref PubMed Scopus (160) Google Scholar, Scott et al., 2014Scott K.P. Martin J.C. Duncan S.H. Flint H.J. Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro.FEMS Microbiol. Ecol. 2014; 87: 30-40Crossref PubMed Scopus (278) Google Scholar). We observed a non-significant increase in the abundance of Akkermansia muciniphila and no change in the abundance of Bacteroides thetaiotaomicron or Eubacterium rectale in SIM mice that switched from chow to an HF-HS or a ZF-HS diet (Figure 2A), consistent with the fact that these bacteria are not exclusively dependent on dietary fiber and can degrade host mucin or simple sugars from the diet. A. muciniphila is an avid user of mucin glycans (Derrien et al., 2004Derrien M. Vaughan E.E. Plugge C.M. de Vos W.M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium.Int. J. Syst. Evol. Microbiol. 2004; 54: 1469-1476Crossref PubMed Scopus (1185) Google Scholar). B. thetaiotaomicron is able to digest a broad range of dietary polysaccharides and adapts to different sources of carbohydrates, including mucin glycans, in the absence of dietary fibers (Sonnenburg et al., 2005Sonnenburg J.L. Xu J. Leip D.D. Chen C.-H. Westover B.P. Weatherford J. Buhler J.D. Gordon J.I. Glycan foraging in vivo by an intestine-adapted bacterial symbiont.Science. 2005; 307: 1955-1959Crossref PubMed Scopus (827) Google Scholar). E. rectale can metabolize different carbohydrates (amylopectin, amylose, arabinoxylan, fructo-oligosaccharide, galacto-oligosaccharide, inulin, xylo-oligosaccharide) (Sheridan et al., 2016Sheridan P.O. Martin J.C. Lawley T.D. Browne H.P. Harris H.M.B. Bernalier-Donadille A. Duncan S.H. O’Toole P.W. Scott K.P. Flint H.J. Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes.Microb. Genom. 2016; 2: e000043Crossref PubMed Scopus (133) Google Scholar) but has also been shown to grow well on glucose (Cockburn et al., 2015Cockburn D.W. Orlovsky N.I. Foley M.H. Kwiatkowski K.J. Bahr C.M. Maynard M. Demeler B. Koropatkin N.M. Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale.Mol. Microbiol. 2015; 95: 209-230Crossref PubMed Scopus (78) Google Scholar, Ze et al., 2012Ze X. Duncan S.H. Louis P. Flint H.J. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon.ISME J. 2012; 6: 1535-1543Crossref PubMed Scopus (576) Google Scholar). The abundance of D. piger was also not affected by a change in diet (Figure 2A). The growth and survival of D. piger is dependent on the availability of sulfate (Rey et al., 2013Rey F.E. Gonzalez M.D. Cheng J. Wu M. Ahern P.P. Gordon J.I. Metabolic niche of a prominent sulfate-reducing human gut bacterium.Proc. Natl. Acad. Sci. U S A. 2013; 110: 13582-13587Crossref PubMed Scopus (240) Google Scholar), which in the mammalian gut is sourced not only from the diet but also from sulfated glycans in host mucin. Although D. piger lacks sulfatase activity, A. muciniphila and B. thetaiotaomicron are capable of removing sulfate from sulfated glycans when metabolizing host glycans and thus can contribute to the availability of sulfate required by D. piger (Rey et al., 2013Rey F.E. Gonzalez M.D. Cheng J. Wu M. Ahern P.P. Gordon J.I. Metabolic niche of a prominent sulfate-reducing human gut bacterium.Proc. Natl. Acad. Sci. U S A. 2013; 110: 13582-13587Crossref PubMed Scopus (240) Google Scholar). There were no significant differences in individual bacterial species between mice on an HF-HS or a ZF-HS diet (Figure 2A), indicating that a reduction in plant polysaccharides has a greater influence on the abundance of the SIM members than variations in either fat or sucrose. We confirmed the functional capacity of the SIM community to metabolize carbohydrates by showing that levels of SCFAs and organic acids were dramatically higher in cecal samples from SIM mice compared with GF mice on a chow diet (Figure 2B). To investigate the functional response of the SIM microbiota to" @default.
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- W2924130156 date "2019-03-01" @default.
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- W2924130156 title "Simplified Intestinal Microbiota to Study Microbe-Diet-Host Interactions in a Mouse Model" @default.
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