The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications

Jason R Goldsmith, R Balfour Sartor, Jason R Goldsmith, R Balfour Sartor

Abstract

Dietary impacts on health may be one of the oldest concepts in medicine; however, only in recent years have technical advances in mass spectroscopy, gnotobiology, and bacterial sequencing enabled our understanding of human physiology to progress to the point where we can begin to understand how individual dietary components can affect specific illnesses. This review explores the current understanding of the complex interplay between dietary factors and the host microbiome, concentrating on the downstream implications on host immune function and the pathogenesis of disease. We discuss the influence of the gut microbiome on body habitus and explore the primary and secondary effects of diet on enteric microbial community structure. We address the impact of consumption of non-digestible polysaccharides (prebiotics and fiber), choline, carnitine, iron, and fats on host health as mediated by the enteric microbiome. Disease processes emphasized include non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, IBD, and cardiovascular disease/atherosclerosis. The concepts presented in this review have important clinical implications, although more work needs to be done to develop fully and validate potential therapeutic approaches. Specific dietary interventions offer exciting potential for nontoxic, physiologic ways to alter enteric microbial structure and metabolism to benefit the natural history of many intestinal and systemic disorders.

Conflict of interest statement

Disclosures/Conflicts of Interest: JRG discloses that he is a technical consultant for Protagonist Therapuetics (Milpitas, CA), RBS is member of the United States Probiotic Council (Dannon and Yakult Companies)

Figures

Figure 1. The complex interplay of dietary…
Figure 1. The complex interplay of dietary elements, the microbiota, and the host can be beneficial or detrimental to host health
Milk fat (blue): increased consumption of milk fat leads to increased levels of taurine-conjugated bile acids, which result in a bloom of Bilophila wadsworthia, a colitogenic H2Sproducing bacteria. Fiber (pink): Consumption of fiber leads to the production of butyrate and other short-chain fatty acids by colonic bacteria. These SCFAs promote epithelial healing and decrease intestinal inflammation, in part through induction of Tregs. Choline/carnitine (green): Dysbiotic states, as found naturally in a subset of patients or in patients with IBD, results in the increased bacterial metabolism of choline and/or carnitine to TMA. This decreases the bioavailability of choline, leading to NAFLD/NASH, while increased levels of TMA are metabolized by the liver to TMAO, an atherosclerotic compound. Iron (black): Increased oral iron intake is associated with increased intestinal epithelial cell stress and cell death and altered microbiota profiles, which may exacerbate active IBD.

References

    1. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–249.
    1. Sartor RB. Microbial Influences in Inflammatory Bowel Diseases. Gastroenterology. 2008;134(2):577–594.
    1. Knights D, Lassen KG, Xavier RJ. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut. 2013;62(10):1505–1510.
    1. Ng SC, Tang W, Ching JY, Wong M, Chow CM, Hui AJ, et al. Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study. Gastroenterology. 2013;145(1):158–165. e2.
    1. Erickson AR, Cantarel BL, Lamendella R, Darzi Y, Mongodin EF, Pan C, et al. Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease. PloS one. 2012;7(11):e49138.
    1. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180.
    1. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(3):979–984.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–108.
    1. Zimmer J, Lange B, Frick JS, Sauer H, Zimmermann K, Schwiertz A, et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. European journal of clinical nutrition. 2012;66(1):53–60.
    1. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2013
    1. Lynch JB, Sonnenburg JL. Prioritization of a plant polysaccharide over a mucus carbohydrate is enforced by a Bacteroides hybrid two-component system. Molecular microbiology. 2012;85(3):478–491.
    1. Fukuda S, Ohno H. Gut microbiome and metabolic diseases. Seminars in immunopathology. 2014;36(1):103–114.
    1. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(31):11070–11075.
    1. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–484.
    1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031.
    1. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–546.
    1. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(43):16731–16736.
    1. Sonnenburg JL, Xu J, Leip DD, Chen CH, Westover BP, Weatherford J, et al. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science. 2005;307(5717):1955–1959.
    1. Sonnenburg ED, Sonnenburg JL, Manchester JK, Hansen EE, Chiang HC, Gordon JI. A hybrid twocomponent system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(23):8834–8839.
    1. Reyes A, Semenkovich NP, Whiteson K, Rohwer F, Gordon JI. Going viral: next-generation sequencing applied to phage populations in the human gut. Nature reviews Microbiolog. 2012;10(9):607–617.
    1. Lepage P, Colombet J, Marteau P, Sime-Ngando T, Dore J, Leclerc M. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut. 2008;57(3):424–425.
    1. Ogilvie LA, Bowler LD, Caplin J, Dedi C, Diston D, Cheek E, et al. Genome signature-based dissection of human gut metagenomes to extract subliminal viral sequences. Nature communications. 2013;4:2420.
    1. Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. Journal of clinical gastroenterology. 2006;40(3):235–243.
    1. Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon. The Journal of applied bacteriology. 1991;70(6):443–459.
    1. Roediger WE. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980;21(9):793–798.
    1. Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty acid irrigation. The New England journal of medicine. 1989;320(1):23–28.
    1. Guillemot F, Colombel JF, Neut C, Verplanck N, Lecomte M, Romond C, et al. Treatment of diversion colitis by short-chain fatty acids. Prospective and double-blind study. Diseases of the colon and rectum. 1991;34(10):861–864.
    1. Pacheco RG, Esposito CC, Muller LC, Castelo-Branco MT, Quintella LP, Chagas VL, et al. Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis. World journal of gastroenterology : WJG. 2012;18(32):4278–4287.
    1. Breuer RI, Buto SK, Christ ML, Bean J, Vernia P, Paoluzi P, et al. Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report. Digestive diseases and sciences. 1991;36(2):185–187.
    1. Cummings JH. Short-chain fatty acid enemas in the treatment of distal ulcerative colitis. European journal of gastroenterology & hepatology. 1997;9(2):149–153.
    1. Scheppach W. Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Digestive diseases and sciences. 1996;41(11):2254–2259.
    1. Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992;103(1):51–56.
    1. Patz J, Jacobsohn WZ, Gottschalk-Sabag S, Zeides S, Braverman DZ. Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas. The American journal of gastroenterology. 1996;91(4):731–734.
    1. Steinhart AH, Hiruki T, Brzezinski A, Baker JP. Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial. Alimentary pharmacology & therapeutics. 1996;10(5):729–736.
    1. Breuer RI, Soergel KH, Lashner BA, Christ ML, Hanauer SB, Vanagunas A, et al. Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial. Gut. 1997;40(4):485–491.
    1. Saemann MD, Bohmig GA, Osterreicher CH, Burtscher H, Parolini O, Diakos C, et al. Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000;14(15):2380–2382.
    1. Menzel T, Luhrs H, Zirlik S, Schauber J, Kudlich T, Gerke T, et al. Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1. Inflammatory bowel diseases. 2004;10(2):122–128.
    1. Zimmerman MA, Singh N, Martin PM, Thangaraju M, Ganapathy V, Waller JL, et al. Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells. American journal of physiology Gastrointestinal and liver physiology. 2012;302(12):G1405–G1415.
    1. Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L. Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. Molecular cancer research : MCR. 2003;1(11):855–862.
    1. Schreiber S, Rosenstiel P, Hampe J, Nikolaus S, Groessner B, Schottelius A, et al. Activation of signal transducer and activator of transcription (STAT) 1 in human chronic inflammatory bowel disease. Gut. 2002;51(3):379–385.
    1. Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. 2000;47(3):397–403.
    1. Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proceedings of the National Academy of Sciences. 2014
    1. Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D. Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J Nutr Biochem. 2008;19(9):587–593.
    1. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–573.
    1. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455.
    1. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–450.
    1. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40(1):128–139.
    1. Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232–236.
    1. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(34):13780–13785.
    1. Mahowald MA, Rey FE, Seedorf H, Turnbaugh PJ, Fulton RS, Wollam A, et al. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(14):5859–5864.
    1. Thomas F, Hehemann JH, Rebuffet E, Czjzek M, Michel G. Environmental and gut bacteroidetes: the food connection. Frontiers in microbiology. 2011;2:93.
    1. Li E, Hamm CM, Gulati AS, Sartor RB, Chen H, Wu X, et al. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition. PloS one. 2012;7(6):e26284.
    1. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2013
    1. Rajilic-Stojanovic M, Shanahan F, Guarner F, de Vos WM. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflammatory bowel diseases. 2013;19(3):481–488.
    1. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nature reviews Gastroenterology & hepatology. 2011;8(1):17–26.
    1. Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, Rand KH, et al. Intestinal Dysbiosis and Depletion of Butyrogenic Bacteria in Clostridium difficile Infection and Nosocomial Diarrhea. Journal of clinical microbiology. 2013;51(9):2884–2892.
    1. Di Sabatino A, Morera R, Ciccocioppo R, Cazzola P, Gotti S, Tinozzi FP, et al. Oral butyrate for mildly to moderately active Crohn's disease. Alimentary pharmacology & therapeutics. 2005;22(9):789–794.
    1. Vance DE. Role of phosphatidylcholine biosynthesis in the regulation of lipoprotein homeostasis. Current opinion in lipidology. 2008;19(3):229–234.
    1. Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. The Journal of nutrition. 2003;133(5):1302–1307.
    1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic proceedings Mayo Clinic. 1980;55(7):434–438.
    1. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Annals of internal medicine. 1997;126(2):137–145.
    1. Charlton M. Cirrhosis and liver failure in nonalcoholic fatty liver disease: Molehill or mountain? Hepatology. 2008;47(5):1431–1433.
    1. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179–185.
    1. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37(5):1202–1219. Epub 2003/04/30.
    1. Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology. 2011;140(3):976–986.
    1. Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(44):18933–18938.
    1. Werner T, Hoermannsperger G, Schuemann K, Hoelzlwimmer G, Tsuji S, Haller D. Intestinal epithelial cell proteome from wild-type and TNFDeltaARE/WT mice: effect of iron on the development of chronic ileitis. Journal of proteome research. 2009;8(7):3252–3264.
    1. Gulati AS, Shanahan MT, Arthur JC, Grossniklaus E, von Furstenberg RJ, Kreuk L, et al. Mouse background strain profoundly influences Paneth cell function and intestinal microbial composition. PloS one. 2012;7(2):e32403.
    1. Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(33):12511–12516.
    1. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145(5):745–757.
    1. Karrasch T, Kim J-S, Muhlbauer M, Magness ST, Jobin C. Gnotobiotic IL-10−/−;NF-{kappa}BEGFP Mice Reveal the Critical Role of TLR/NF-{kappa}B Signaling in Commensal Bacteria-Induced Colitis. J Immunol. 2007;178(10):6522–6532.
    1. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998;66(11):5224–5231. Epub 1998/10/24.
    1. Martin FP, Rezzi S, Philippe D, Tornier L, Messlik A, Holzlwimmer G, et al. Metabolic assessment of gradual development of moderate experimental colitis in IL-10 deficient mice. Journal of proteome research. 2009;8(5):2376–2387.
    1. Murdoch TB, Fu H, MacFarlane S, Sydora BC, Fedorak RN, Slupsky CM. Urinary Metabolic Profiles of Inflammatory Bowel Disease in Interleukin-10 Gene-Deficient Mice. Analytical Chemistry. 2008;80(14):5524–5531.
    1. Bjerrum JT, Nielsen OH, Hao F, Tang H, Nicholson JK, Wang Y, et al. Metabonomics in Ulcerative Colitis: Diagnostics, Biomarker Identification, And Insight into the Pathophysiology. Journal of proteome research. 2009;9(2):954–962.
    1. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. The American journal of clinical nutrition. 2010;91(3):535–546.
    1. Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation. 2010;121(21):2271–2283.
    1. Lang DH, Yeung CK, Peter RM, Ibarra C, Gasser R, Itagaki K, et al. Isoform specificity of trimethylamine N-oxygenation by human flavin-containing monooxygenase (FMO) and P450 enzymes: selective catalysis by FMO3. Biochemical pharmacology. 1998;56(8):1005–1012.
    1. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.
    1. Aloi M, Tromba L, Di Nardo G, Dilillo A, Del Giudice E, Marocchi E, et al. Premature subclinical atherosclerosis in pediatric inflammatory bowel disease. The Journal of pediatrics. 2012;161(4):589–594. e1.
    1. Rungoe C, Basit S, Ranthe MF, Wohlfahrt J, Langholz E, Jess T. Risk of ischaemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study. Gut. 2013;62(5):689–694.
    1. Yarur AJ, Deshpande AR, Pechman DM, Tamariz L, Abreu MT, Sussman DA. Inflammatory bowel disease is associated with an increased incidence of cardiovascular events. The American journal of gastroenterology. 2011;106(4):741–747.
    1. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature medicine. 2013;19(5):576–585.
    1. Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annual review of nutrition. 1998;18:39–61.
    1. Polin V, Coriat R, Perkins G, Dhooge M, Abitbol V, Leblanc S, et al. Iron deficiency: From diagnosis to treatment. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2013;45(10):803–809.
    1. Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn's disease. Alimentary pharmacology & therapeutics. 2006;24(11–12):1507–1523.
    1. Gisbert JP, Bermejo F, Pajares R, Perez-Calle JL, Rodriguez M, Algaba A, et al. Oral and intravenous iron treatment in inflammatory bowel disease: hematological response and quality of life improvement. Inflammatory bowel diseases. 2009;15(10):1485–1491.
    1. Erichsen K, Ulvik RJ, Nysaeter G, Johansen J, Ostborg J, Berstad A, et al. Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease. Scandinavian journal of gastroenterology. 2005;40(9):1058–1065.
    1. Lindgren S, Wikman O, Befrits R, Blom H, Eriksson A, Granno C, et al. Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study. Scandinavian journal of gastroenterology. 2009;44(7):838–845.
    1. Reifen R, Matas Z, Zeidel L, Berkovitch Z, Bujanover Y. Iron supplementation may aggravate inflammatory status of colitis in a rat model. Digestive diseases and sciences. 2000;45(2):394–397.
    1. Seril DN, Liao J, Ho KL, Warsi A, Yang CS, Yang GY. Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice. Digestive diseases and sciences. 2002;47(6):1266–1278.
    1. Knobel Y, Glei M, Osswald K, Pool-Zobel BL. Ferric iron increases ROS formation, modulates cell growth and enhances genotoxic damage by 4-hydroxynonenal in human colon tumor cells. Toxicology in vitro : an international journal published in association with BIBRA. 2006;20(6):793–800.
    1. Kaser A, Martinez-Naves E, Blumberg RS. Endoplasmic reticulum stress: implications for inflammatory bowel disease pathogenesis. Curr Opin Gastroenterol. 2010;26(4):318–326. Epub 2010/05/25.
    1. Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell. 2008;134(5):743–756. Epub 2008/09/09.
    1. Brandl K, Rutschmann S, Li X, Du X, Xiao N, Schnabl B, et al. Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(9):3300–3305.
    1. Goldsmith JR, Cocchiaro JL, Rawls JF, Jobin C. Glafenine-induced intestinal injury in zebrafish is ameliorated by mu-opioid signaling via enhancement of Atf6-dependent cellular stress responses. Dis Model Mech. 2012;6(1):146–159. Epub 2012/08/25.
    1. Kaser A, Blumberg RS. Autophagy, microbial sensing, endoplasmic reticulum stress, and epithelial function in inflammatory bowel disease. Gastroenterology. 2011;140(6):1738–1747. Epub 2011/05/03.
    1. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008;456(7219):259–263. Epub 2008/10/14.
    1. Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nature medicine. 2010;16(1):90–97.
    1. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhaes JG, et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nature immunology. 2010;11(1):55–62.
    1. Werner T, Wagner SJ, Martinez I, Walter J, Chang JS, Clavel T, et al. Depletion of luminal iron alters the gut microbiota and prevents Crohn's disease-like ileitis. Gut. 2011;60(3):325–333.
    1. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, et al. Dietary-fatinduced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature. 2012;487(7405):104–108.
    1. Miller TW, Wang EA, Gould S, Stein EV, Kaur S, Lim L, et al. Hydrogen sulfide is an endogenous potentiator of T cell activation. The Journal of biological chemistry. 2012;287(6):4211–4221.
    1. Pitcher MC, Cummings JH. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut. 1996;39(1):1–4.
    1. Laue H, Denger K, Cook AM. Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU. Applied and environmental microbiology. 1997;63(5):2016–2021.
    1. Lindstedt S, Avigan J, Goodman DS, Sjovall J, Steinberg D. The effect of dietary fat on the turnover of cholic acid and on the composition of the biliary bile acids in man. The Journal of clinical investigation. 1965;44(11):1754–1765.
    1. Truelove SC. Ulcerative colitis provoked by milk. British medical journal. 1961;1(5220):154–160.
    1. Taylor KB, Truelove SC. Circulating antibodies to milk proteins in ulcerative colitis. British medical journal. 1961;2(5257):924–929.
    1. Jewell DP, Truelove SC. Circulating antibodies to cow's milk proteins in ulcerative colitis. Gut. 1972;13(10):796–801.
    1. Mbodji K, Charpentier C, Guerin C, Querec C, Bole-Feysot C, Aziz M, et al. Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-kappaB in rats with TNBS-induced colitis. J Nutr Biochem. 2013;24(4):700–705.
    1. Monk JM, Hou TY, Turk HF, Weeks B, Wu C, McMurray DN, et al. Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis. PloS one. 2012;7(11):e49739.
    1. Whiting CV, Bland PW, Tarlton JF. Dietary n-3 polyunsaturated fatty acids reduce disease and colonic proinflammatory cytokines in a mouse model of colitis. Inflammatory bowel diseases. 2005;11(4):340–349.
    1. Monk JM, Jia Q, Callaway E, Weeks B, Alaniz RC, McMurray DN, et al. Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) PUFA in Fat-1 mice. The Journal of nutrition. 2012;142(1):117–124.
    1. Okada Y, Tsuzuki Y, Sato H, Narimatsu K, Hokari R, Kurihara C, et al. Trans fatty acids exacerbate dextran sodium sulphate-induced colitis by promoting the up-regulation of macrophage-derived proinflammatory cytokines involved in T helper 17 cell polarization. Clinical and experimental immunology. 2013;174(3):459–471.
    1. Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. The New England journal of medicine. 1996;334(24):1557–1560.
    1. Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D'Haens G, Bradette M, et al. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA : the journal of the American Medical Association. 2008;299(14):1690–1697.
    1. Cohen AB, Lee D, Long MD, Kappelman MD, Martin CF, Sandler RS, et al. Dietary patterns and self-reported associations of diet with symptoms of inflammatory bowel disease. Digestive diseases and sciences. 2013;58(5):1322–1328.
    1. Gasche C, Dejaco C, Waldhoer T, Tillinger W, Reinisch W, Fueger GF, et al. Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial. Annals of internal medicine. 1997;126(10):782–787.
    1. Stein J, Bager P, Befrits R, Gasche C, Gudehus M, Lerebours E, et al. Anaemia management in patients with inflammatory bowel disease: routine practice across nine European countries. European journal of gastroenterology & hepatology. 2013;25(12):1456–1463.
    1. Vavricka SR, Schoepfer AM, Safroneeva E, Rogler G, Schwenkglenks M, Achermann R. A shift from oral to intravenous iron supplementation therapy is observed over time in a large swiss cohort of patients with inflammatory bowel disease. Inflammatory bowel diseases. 2013;19(4):840–846.
    1. Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–184.
    1. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome. Gastroenterology. 2013
    1. Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, Marietta E, O'Neill J, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013;144(5):903–911. e3.
    1. Peery AF, Barrett PR, Park D, Rogers AJ, Galanko JA, Martin CF, et al. A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology. 2012;142(2):266–272. e1.
    1. Sharara AI, El-Halabi MM, Mansour NM, Malli A, Ghaith OA, Hashash JG, et al. Alcohol consumption is a risk factor for colonic diverticulosis. Journal of clinical gastroenterology. 2013;47(5):420–425.
    1. Catassi C, Kryszak D, Bhatti B, Sturgeon C, Helzlsouer K, Clipp SL, et al. Natural history of celiac disease autoimmunity in a USA cohort followed since 1974. Annals of medicine. 2010;42(7):530–538.

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