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Review Articles

Inflammatory bowel disease: tri-directional relationship between microbiota, immune system and intestinal epithelium

, , , & ORCID Icon
Pages 254-273 | Received 03 Oct 2020, Accepted 06 Jan 2021, Published online: 12 Feb 2021

References

  • Adjimani JP, Asare P. 2015. Antioxidant and free radical scavenging activity of iron chelators. Toxicol Rep. 2:721–728.
  • Ahlawat S, Asha Sharma KK. 2020a. Gut-organ axis: a microbial outreach and networking. Lett Appl Microbiol. DOI:10.1111/lam.13333.
  • Ahlawat S, Asha Sharma KK. 2020b. Immunological co-ordination between gut and lungs in SARS-CoV-2 infection. Virus Res. 286:198103.
  • Alam MT, Amos GC, Murphy AR, Murch S, Wellington EM, Arasaradnam RP. 2020. Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels. Gut Pathog. 12:1.
  • Alatise OI, Otegbayo JA, Nwosu MN, Lawal OO, Ola SO, Anyanwu SN, Ndububa DA, Akere A, Odike MA, Agbakwuru EA, et al. 2012. Characteristics of inflammatory bowel disease in three tertiary health centers in Southern Nigeria. West Afr J Med. 31:28–33.
  • Alex P, Gucek M, Li X. 2009. Applications of proteomics in the study of inflammatory bowel diseases: current status and future directions with available technologies. Inflamm Bowel Dis. 15:616–629.
  • Allegretti JR, Mullish BH, Kelly C, Fischer M. 2019. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet. 394:420–431.
  • Amaretti A, di Nunzio M, Pompei A, Raimondi S, Rossi M, Bordoni A. 2013. Antioxidant properties of potentially probiotic bacteria: in vitro and in vivo activities. Appl Microbiol Biotechnol. 97:809–817.
  • Amon P, Sanderson I. 2017. What is the microbiome? Arch Dis Child Educ Pract Ed. 102:257–261.
  • Ananthakrishnan AN. 2015. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 12:205–217.
  • Assa A, Butcher J, Li J, Elkadri A, Sherman PM, Muise AM, Stintzi A, Mack D. 2016. Mucosa-associated ileal microbiota in new-onset pediatric crohn’s disease. Inflamm Bowel Dis. 22:1533–1539.
  • Bai AHC, Wu WKK, Xu L, Wong SH, Go MY, Chan AWH, Harbord M, Zhang S, Chen M, Wu JCY, et al. 2016. Dysregulated lysine acetyltransferase 2B promotes inflammatory bowel disease pathogenesis through transcriptional repression of interleukin-10. J Crohns Colitis. 10:726–734.
  • Basset C, Holton J, O’Mahony R, Roitt I. 2003. Innate immunity and pathogen–host interaction. Vaccine. 21:S12–S23.
  • Becker C, Neurath MF, Wirtz S. 2015. The intestinal microbiota in inflammatory bowel disease. Ilar J. 56:192–204.
  • Biancheri P, Di Sabatino A, Corazza GR, MacDonald TT. 2013. Proteases and the gut barrier. Cell Tissue Res. 351:269–280.
  • Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. 2016. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 8:42.
  • Brew K, Nagase H. 2010. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta. 1803:55–71.
  • Bringiotti R, Ierardi E, Lovero R, Losurdo G, Di Leo A, Principi M. 2014. Intestinal microbiota: the explosive mixture at the origin of inflammatory bowel disease? World J Gastrointest Pathophysiol. 5:550–559.
  • Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJL, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, et al. 2015. Variation in the human immune system is largely driven by non-heritable influences. Cell. 160:37–47.
  • Buisine MP, Desreumaux P, Leteurtre E, Copin MC, Colombel JF, Porchet N, Aubert JP. 2001. Mucin gene expression in intestinal epithelial cells in Crohn’s disease. Gut. 49:544–551.
  • Cader MZ, Kaser A. 2013. Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation. Gut. 62:1653–1664.
  • Cadwell K. 2015. The virome in host health and disease. Immunity. 42:805–813.
  • Caruso R, Lo BC, Núñez G. 2020. Host-microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 20:411–416.
  • Chan PPY, Wasinger VC, Leong RW. 2016. Current application of proteomics in biomarker discovery for inflammatory bowel disease. World J Gastrointest Pathophysiol. 7:27–37.
  • Cho H, Kelsall BL. 2014. The role of type I interferons in intestinal infection, homeostasis, and inflammation. Immunol Rev. 260:145–167.
  • Clevers HC, Bevins CL. 2013. Paneth cells: maestros of the small intestinal crypts. Annu Rev Physiol. 75:289–311.
  • Cleynen I, Jüni P, Bekkering GE, Nüesch E, Mendes CT, Schmied S, Wyder S, Kellen E, Villiger PM, Rutgeerts P, et al. 2011. Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. PLoS One. 6:e24106.
  • Colgan SP, Taylor CT. 2010. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol. 7:281–287.
  • Cominelli F, Arseneau KO, Rodriguez-Palacios A, Pizarro TT. 2017. Uncovering pathogenic mechanisms of inflammatory bowel disease using mouse models of Crohn’s disease-like ileitis: what is the right model? Cell Mol Gastroenterol Hepatol. 4:19–32.
  • Curová K, Kmetová M, Sabol M, Gombosová L, Lazúrová I, Siegfried L. 2009. Enterovirulent E. coli in inflammatory and noninflammatory bowel diseases. Folia Microbiol (Praha). 54:81–86.
  • Das B, Nair GB. 2019. Homeostasis and dysbiosis of the gut microbiome in health and disease. J Biosci. 44:117.
  • Dave M, Papadakis KA, Faubion WA. 2014. Immunology of inflammatory bowel disease and molecular targets for biologics. Gastroenterol Clin North Am. 43:405–424.
  • Dave M, Mehta K, Luther J, Baruah A, Dietz AB, Faubion WA. 2015. Mesenchymal stem cell therapy for inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 21:2696–2707.
  • Deeke SA, Starr AE, Ning Z, Ahmadi S, Zhang X, Mayne J, Chiang CK, Singleton R, Benchimol EI, Mack DR, et al. 2018.  Mucosal-luminal interface proteomics reveals biomarkers of pediatric inflammatory bowel disease-associated colitis. Am J Gastroenterol. 113:713–724.
  • Diab J, Al-Mahdi R, Gouveia-Figueira S, Hansen T, Jensen E, Goll R, Moritz T, Florholmen J, Forsdahl G. 2019. A quantitative analysis of colonic mucosal oxylipins and endocannabinoids in treatment-naïve and deep remission ulcerative colitis patients and the potential link with cytokine gene expression. Inflamm Bowel Dis. 25:490–497.
  • Dorofeyev AE, Vasilenko IV, Rassokhina OA, Kondratiuk RB. 2013. Mucosal barrier in ulcerative colitis and Crohn’s disease. Gastroenterol Res Pract. 2013:431231.
  • Douglas GM, Hansen R, Jones CMA, Dunn KA, Comeau AM, Bielawski JP, Tayler R, El-Omar EM, Russell RK, Hold GL, et al. 2018. Multi-omics differentially classify disease state and treatment outcome in pediatric Crohn’s disease. Microbiome. 6:13.
  • Dovrolis N, Filidou E, Kolios G. 2019. Systems biology in inflammatory bowel diseases: on the way to precision medicine. Ann Gastroenterol. 32:233–246.
  • Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, et al. 2013. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 62:531–539.
  • Edgington-Mitchell LE. 2016. Pathophysiological roles of proteases in gastrointestinal disease. Am J Physiol Gastrointest Liver Physiol. 310:G234–G239.
  • Eppinga H, Fuhler GM, Peppelenbosch MP, Hecht GA. 2016. Gut microbiota developments with emphasis on inflammatory bowel disease: report from the Gut Microbiota for Health World Summit 2016. Gastroenterology. 151:e1–e4.
  • Fang B, Li JW, Zhang M, Ren FZ, Pang GF. 2018. Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats. Food Chem Toxicol. 111:144–152.
  • Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. 2020. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut. DOI:10.1136/gutjnl-2020-321747.
  • Fernández AF, López-Otín C. 2015. The functional and pathologic relevance of autophagy proteases. J Clin Invest. 125:33–41..
  • Fletcher J, Cooper SC, Ghosh S, Hewison M. 2019. The role of vitamin D in inflammatory bowel disease: mechanism to management. Nutrients. 11:1019.
  • Fofanova TY, Petrosino JF, Kellermayer R. 2016. Microbiome-epigenome interactions and the environmental origins of inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. 62:208–219.
  • Frenkel S, Bernstein CN, Sargent M, Kuang Q, Jiang W, Wei J, Thiruvahindrapuram B, Spriggs E, Scherer SW, Hu P. 2019. Genome wide analysis identifies rare copy number variations associated with inflammatory bowel disease. PLoS One. 14:e0217846.
  • Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. 2014. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 13:3–10.
  • Ghosh R, Alajbegovic A, Gomes AV. 2015. NSAIDs and cardiovascular diseases: role of reactive oxygen species. Oxid Med Cell Longev. 2015:536962.
  • Ghosh S, Heel D, Playford RJ. 2004. Probiotics in inflammatory bowel disease: is it all gut flora modulation? Gut. 53:620–622.
  • Gibson PR, Muir JG. 2005. Reinforcing the mucus: a new therapeutic approach for ulcerative colitis? Gut. 54:900–903.
  • Glassner KL, Abraham BP, Quigley EM. 2020. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol. 145:16–27.
  • Goll R, Granlund AVB. 2015. Intestinal barrier homeostasis in inflammatory bowel disease. Scand J Gastroenterol. 50:3–12.
  • Goretsky T, Dirisina R, Sinh P, Mittal N, Managlia E, Williams DB, Posca D, Ryu H, Katzman RB, Barrett TA. 2012. p53 mediates TNF-induced epithelial cell apoptosis in IBD. Am J Pathol. 181:1306–1315.
  • Goswami P, Das P, Verma AK, Prakash S, Das TK, Nag TC, Ahuja V, Gupta SD, Makharia GK. 2014. Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn’s disease? Virchows Arch. 465:521–530.
  • Greuter T, Navarini A, Vavricka SR. 2017. Skin manifestations of inflammatory bowel disease. Clin Rev Allergy Immunol. 53:413–427.
  • Groeger D, O'Mahony L, Murphy EF, Bourke JF, Dinan TG, Kiely B, Shanahan F, Quigley EMM. 2013. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 4:325–339.
  • Günther C, Buchen B, Neurath MF, Becker C. 2014. Regulation and pathophysiological role of epithelial turnover in the gut. Semin Cell Dev Biol. 35:40–50.
  • Halliwell B. 1991. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 91:14–22.
  • Halliwell B, Gutteridge JMC. 1999. Free radicals in biology and medicine. In: Halliwell B, Gutteridge JMC, editors. Free radicals in biology and medicine. 3rd ed. Oxford (UK): Oxford University Press; p. 1–25.
  • Ho S, Pothoulakis C, Koon HW. 2013. Antimicrobial peptides and colitis. Curr Pharm Des. 19:40–47.
  • Howell KJ, Kraiczy J, Nayak KM, Gasparetto M, Ross A, Lee C, Mak TN, Koo BK, Kumar N, Lawley T, et al. 2018. DNA methylation and transcription patterns in intestinal epithelial cells from pediatric patients with inflammatory bowel diseases differentiate disease subtypes and associate with outcome. Gastroenterology. 154:585–598.
  • Jäger S, Stange EF, Wehkamp J. 2013. Inflammatory bowel disease: an impaired barrier disease. Langenbecks Arch Surg. 398:1–12.
  • Jeon SR, Chai J, Kim C, Lee CH. 2018. Current evidence for the management of inflammatory bowel diseases using fecal microbiota transplantation. Curr Infect Dis Rep. 20:21.
  • Jiang W, Li X. 2015. Molecular analysis of inflammatory bowel disease: clinically useful tools for diagnosis, response prediction, and monitoring of targeted therapy. Mol Diagn Ther. 19:141–158.
  • Jochum L, Stecher B. 2020. Label or concept - what is a pathobiont? Trends Microbiol. 28:789–792.
  • Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, International IBD Genetics Consortium (IIBDGC), et al. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 491:119–124.
  • Kalla R, Ventham NT, Kennedy NA, Quintana JF, Nimmo ER, Buck AH, Satsangi J. 2015. MicroRNAs: new players in IBD. Gut. 64:504–514.
  • Kaser A, Zeissig S, Blumberg RS. 2010. Inflammatory bowel disease. Annu Rev Immunol. 28:573–621.
  • Kathiria AS, Butcher MA, Hansen JM, Theiss AL. 2013. Nrf2 is not required for epithelial prohibitin-dependent attenuation of experimental colitis. Am J Physiol Gastrointest Liver Physiol. 304:G885–G896.
  • Katsanos KH, Papadakis KA. 2017. Inflammatory bowel disease: updates on molecular targets for biologics. Gut Liver. 11:455–463.
  • Keshteli AH, van den Brand FF, Madsen KL, Mandal R, Valcheva R, Kroeker KI, Han B, Bell RC, Cole J, Hoevers T, et al. 2017. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: a pilot prospective cohort study. World J Gastroenterol. 23:3890–3899.
  • Khan I, Ullah N, Zha L, Bai Y, Khan A, Zhao T, Che T, Zhang C. 2019. Alteration of gut microbiota in inflammatory bowel disease (IBD): cause or consequence? IBD treatment targeting the gut microbiome. Pathogens. 8:126.
  • Klag T, Stange EF, Wehkamp J. 2013. Defective antibacterial barrier in inflammatory bowel disease. Dig Dis. 31:310–316.
  • Knox NC, Forbes JD, Peterson CL, Van Domselaar G, Bernstein CN. 2019. The gut microbiome in inflammatory bowel disease: lessons learned from other immune-mediated inflammatory diseases. Am J Gastroenterol. 114:1051–1070.
  • Koharyova M, Kollarova M. 2008. Oxidative stress and thioredoxin system. Gen Physiol Biophys. 27:71–84.
  • Koslowski MJ, Beisner J, Stange EF, Wehkamp J. 2010. Innate antimicrobial host defense in small intestinal Crohn’s disease. Int J Med Microbiol. 300:34–40.
  • Lagier JC, Dubourg G, Million M, Cadoret F, Bilen M, Fenollar F, Levasseur A, Rolain JM, Fournier PE, Raoult D. 2018. Culturing the human microbiota and culturomics. Nat Rev Microbiol. 16:540–550.
  • Latella G, Fiocchi C, Caprili R. 2010. News from the “5th international meeting on inflammatory bowel diseases” CAPRI 2010. J Crohns Colitis. 4:690–702.
  • Lavelle A, Sokol H. 2020. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 17:223–237.
  • Lee HS, Park S, Park DI. 2018. Novel treatments for inflammatory bowel disease. Korean J Intern Med. 33:20–27.
  • Leong RW. 2010. Environmental risk factors in inflammatory bowel disease. J Gastroenterol Hepatol. 25:325–333.
  • Lewis JD, Albenberg L, Lee D, Kratz M, Gottlieb K, Reinisch W. 2017. The importance and challenges of dietary intervention trials for inflammatory bowel disease. Inflamm Bowel Dis. 23:181–191.
  • Liefferinckx C, Franchimont D. 2018. Viewpoint: toward the genetic architecture of disease severity in inflammatory bowel diseases. Inflamm Bowel Dis. 24:1428–1439.
  • Limbergen J, Radford-Smith G, Satsangi J. 2014. Advances in IBD genetics. Nat Rev Gastroenterol Hepatol. 11:372–385.
  • Liu S, Zhao W, Lan P, Mou X. 2020. The microbiome in inflammatory bowel diseases: from pathogenesis to therapy. Protein Cell..
  • Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, Andrews E, Ajami NJ, Bonham KS, Brislawn CJ, IBDMDB Investigators, et al. 2019. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 569:655–662.
  • Lo Presti A, Zorzi F, Del Chierico F, Altomare A, Cocca S, Avola A, De Biasio F, Russo A, Cella E, Reddel S, et al. 2019. Fecal and mucosal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease. Front Microbiol. 10:1655
  • Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. 2012. Diversity, stability and resilience of the human gut microbiota. Nature. 489:220–230.
  • Lucendo AJ, Rezende LCD. 2009. Importance of nutrition in inflammatory bowel disease. World J Gastroenterol. 15:2081–2088.
  • Maloy KJ, Powrie F. 2011. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 474:298–306.
  • Manfredi M, Conte E, Barberis E, Buzzi A, Robotti E, Caneparo V, Cecconi D, Brandi J, Vanni E, Finocchiaro M, et al. 2019. Integrated serum proteins and fatty acids analysis for putative biomarker discovery in inflammatory bowel disease. J Proteomics. 195:138–149.
  • Martini E, Krug SM, Siegmund B, Neurath MF, Becker C. 2017. Mend your fences: the epithelial barrier and its relationship with mucosal immunity in inflammatory bowel disease. Cell Mol Gastroenterol Hepatol. 4:33–46.
  • McCole DF. 2014. IBD candidate genes and intestinal barrier regulation. Inflamm Bowel Dis. 20:1829–1849.
  • McIlroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold GL. 2018. Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment Pharmacol Ther. 47:26–42.
  • Mcilroy J, Segal JP, Mullish BH, Quraishi MN, Gasbarrini A, Cammarota G, Ianiro G. 2018. Current and future targets for faecal microbiota transplantation. Hum Microbiome J.
  • Meuwis MA, Fillet M, Lutteri L, Marée R, Geurts P, de Seny D, Malaise M, Chapelle JP, Wehenkel L, Belaiche J, et al. 2008. Proteomics for prediction and characterization of response to infliximab in Crohn’s disease: a pilot study. Clin Biochem. 41:960–967.
  • Michelsen KS, Wong MH, Ko B, Thomas LS, Dhall D, Targan SR. 2013. HMPL-004 (Andrographis paniculata extract) prevents development of murine colitis by inhibiting T cell proliferation and TH1/TH17 responses. Inflamm Bowel Dis. 19:151–164.
  • Michielan A, D’Incà R. 2015. Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators Inflamm. 2015:628157.
  • Moayyedi P. 2018. Update on fecal microbiota transplantation in patients with inflammatory bowel disease. Gastroenterol Hepatol (N Y). 14:319–322.
  • Mottawea W, Chiang CK, Mühlbauer M, Starr AE, Butcher J, Abujamel T, Deeke SA, Brandel A, Zhou H, Shokralla S, et al. 2016. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn’s disease. Nat Commun. 7:13419.
  • Moura FA, de Andrade KQ, Dos Santos JCF, Araújo ORP, Goulart MOF. 2015. Antioxidant therapy for treatment of inflammatory bowel disease: does it work? Redox Biol. 6:617–639.
  • Moustafa A, Li W, Anderson EL, Wong EHM, Dulai PS, Sandborn WJ, Biggs W, Yooseph S, Jones MB, Venter JC, et al. 2018. Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease. Clin Transl Gastroenterol. 9:e132.
  • Mukhopadhya I, Segal JP, Carding SR, Hart AL, Hold GL. 2019. The gut virome: the ‘missing link’ between gut bacteria and host immunity? Therap Adv Gastroenterol. 12:1756284819836620.
  • Netzel-Arnett S, Buzza MS, Shea-Donohue T, Désilets A, Leduc R, Fasano A, Bugge TH, Antalis TM. 2012. Matriptase protects against experimental colitis and promotes intestinal barrier recovery. Inflamm Bowel Dis. 18:1303–1314.
  • Neurath MF. 2019. Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol. 20:970–979.
  • Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science. 336:1262–1267.
  • Novak EA, Mollen KP. 2014. Mitochondrial dysfunction in inflammatory bowel disease. Front Cell Dev Biol. 3:62.
  • ÓConnor A, Moss AC. 2014. Current and emerging maintenance therapies for ulcerative colitis. Expert Rev Gastroenterol Hepatol. 8:359–368.
  • ÓHara AM, Shanahan F. 2006. The gut flora as a forgotten organ. EMBO Rep. 7:688–693.
  • ÓToole A, Korzenik J. 2014. Environmental Triggers for IBD. Curr Gastroenterol Rep. 16:396.
  • Oligschlaeger Y, Yadati T, Houben T, Condello Oliván CM, Shiri-Sverdlov R. 2019. Inflammatory bowel disease: a stressed “Gut/Feeling. Cells. 8:659.
  • Orel R, Trop TK. 2014. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World J Gastroenterol. 20:11505–11524.
  • Palmieri O, Mazza T, Castellana S, Panza A, Latiano T, Corritore G, Andriulli A, Latiano A. 2016. Inflammatory bowel disease meets systems biology: a multi-omics challenge and Frontier. OMICS. 20:692–698.
  • Panés J, Gisbert JP. 2019. Efficacy of tofacitinib treatment in ulcerative colitis. Gastroenterol Hepatol. 42:403–412.
  • Panés J, Salas A. 2018. Past, present and future of therapeutic interventions targeting leukocyte trafficking in inflammatory bowel disease. J Crohns Colitis. 12:S633–S640.
  • Parikh K, Antanaviciute A, Fawkner-Corbett D, Jagielowicz M, Aulicino A, Lagerholm C, Davis S, Kinchen J, Chen HH, Alham NK, et al. 2019. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 567:49–55.
  • Pascal V, Pozuelo M, Borruel N, Casellas F, Campos D, Santiago A, Martinez X, Varela E, Sarrabayrouse G, Machiels K, et al. 2017. A microbial signature for Crohn’s disease. Gut. 66:813–822.
  • Patlevič P, Vašková J, Švorc P, Vaško L, Švorc P. 2016. Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integr Med Res. 5:250–258.
  • Peppelenbosch MP, Deventer SJH. 2004. T cell apoptosis and inflammatory bowel disease. Gut. 53:1556–1558.
  • Pérez S, Taléns-Visconti R, Rius-Pérez S, Finamor I, Sastre J. 2016. Redox signaling in the gastrointestinal tract. Free Radic Biol Med. 104:75–103.
  • Pérez-Brocal V, García-López R, Vázquez-Castellanos JF, Nos P, Beltrán B, Latorre A, Moya A. 2013. Study of the viral and microbial communities associated with Crohn’s disease: a metagenomic approach. Clin Transl Gastroenterol. 4:e36.
  • Petrey AC, Motte CA. 2017. The extracellular matrix in IBD: a dynamic mediator of inflammation. Curr Opin Gastroenterol. 33:234–238.
  • Philpott HL, Nandurkar S, Lubel J, Gibson PR. 2014. Drug-induced gastrointestinal disorders. Frontline Gastroenterol. 5:49–57.
  • Piechota-Polanczyk A, Fichna J. 2014. Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases. Naunyn Schmiedebergs Arch Pharmacol. 387:605–620.
  • Poljsak B, Šuput D, Milisav I. 2013. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev. 2013:956792.
  • Ray G, Longworth MS. 2018. Epigenetics, DNA organization, and inflammatory bowel disease. Inflamm Bowel Dis. 25:235–247.
  • Redondo-Useros N, Nova E, González-Zancada N, Díaz LE, Gómez-Martínez S, Marcos A. 2020. Microbiota and lifestyle: a special focus on diet. Nutrients. 12:1776.
  • Rezaie A, Parker RD, Abdollahi M. 2007. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci. 52:2015–2021.
  • Rigottier-Gois L. 2013. Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis. Isme J. 7:1256–1261.
  • Rukmangadachar LA, Makharia GK, Mishra A, Das P, Hariprasad G, Srinivasan A, Gupta SD, Ahuja V, Acharya SK. 2016. Proteome analysis of the macroscopically affected colonic mucosa of Crohn’s disease and intestinal tuberculosis. Sci Rep. 6:23162.
  • Rutgeerts P, Vermeire S, Assche GV. 2009. Reviews in basic and clinical gastroenterology. Gastroenterol. 136:1182–1197.
  • Ryan FJ, Ahern AM, Fitzgerald RS, Laserna-Mendieta EJ, Power EM, Clooney AG, ODonoghue W, McMurdie PJ, Iwai S, Crits-Christoph A, et al. 2020. Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease. Nat. Commun. 11:1–12.
  • Saito S, Kato J, Hiraoka S, Horii J, Suzuki H, Higashi R, Kaji E, Kondo Y, Yamamoto K. 2011. DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status. Inflamm Bowel Dis. 17:1955–1965.
  • Salem M, Ammitzboell M, Nys K, Seidelin JB, Nielsen OH. 2015. ATG16L1: a multifunctional susceptibility factor in Crohn disease. Autophagy. 11:585–594.
  • Sales-Campos H, Basso PJ, Alves VBF, Fonseca MTC, Bonfá G, Nardini V, Cardoso CRB. 2015. Classical and recent advances in the treatment of inflammatory bowel diseases. Braz J Med Biol Res. 48:96–107.
  • Sarbagili-Shabat C, Sigall-Boneh R, Levine A. 2015. Nutritional therapy in inflammatory bowel disease. Curr Opin Gastroenterol. 31:303–308.
  • Sartor RB, Wu GD. 2016. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 152:327–339.e4.
  • Saxena A, Kaur K, Hegde S, Kalekhan FM, Baliga MS, Fayad R. 2014. Dietary agents and phytochemicals in the prevention and treatment of experimental ulcerative colitis. J Tradit Complement Med. 4:203–217.
  • Sbahi H, Palma JAD. 2016. Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders. BMJ Open Gastroenterol. 3:e000087.
  • Scarpignato C. 2008. NSAID-induced intestinal damage: are luminal bacteria the therapeutic target? Gut. 57:145–148.
  • Schirmer M, Garner A, Vlamakis H, Xavier RJ. 2019. Microbial genes and pathways in inflammatory bowel disease. Nat Rev Microbiol. 17:497–511.
  • Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, Ananthakrishnan AN, Andrews E, Barron G, Lake K, et al. 2018. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol. 3:337–346.
  • Schmid M, Fellermann K, Fritz P, Wiedow O, Stange EF, Wehkamp J. 2007. Attenuated induction of epithelial and leukocyte serine antiproteases elafin and secretory leukocyte protease inhibitor in Crohn’s disease. J Leukoc Biol. 81:907–915.
  • Scoville EA, Allaman MM, Brown CT, Motley AK, Horst SN, Williams CS, Koyama T, Zhao Z, Adams DW, Beaulieu DB, et al. 2018. Alterations in lipid, amino acid, and energy metabolism distinguish Crohn’s Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling. Metabolomics. 14:17.
  • Segal JP, Mullish BH, Quraishi MN, Acharjee A, Williams HRT, Iqbal T, Hart AL, Marchesi JR. 2019. The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease. Therap Adv Gastroenterol. 12:1756284818822250.
  • Seifert HS. 2019. Location, location, location-commensalism, damage and evolution of the pathogenic Neisseria. J Mol Biol. 431:3010–3014.
  • Sender R, Fuchs S, Milo R. 2016. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14:e1002533.
  • Shadnoush M, Hosseini RS, Mehrabi Y, Delpisheh A, Alipoor E, Faghfoori Z, Mohammadpour N, Moghadam JZ. 2013. Probiotic yogurt affects pro- and anti-inflammatory factors in patients with inflammatory bowel disease. Iran J Pharm Res. 12:929–936.
  • Shapiro H, Singer P, Halpern Z, Bruck R. 2006. Polyphenols in the treatment of inflammatory bowel disease and acute pancreatitis: the missing ingredient in enteral and parenteral nutrition formulas? Gut..
  • Shastry RP, Rekha PD. 2020. Bacterial cross talk with gut microbiome and its implications: a short review. Folia Microbiol (Praha)..
  • Sidhu M, Poorten D. 2017. The gut microbiome. Aust Fam Physician. 46:206–211.
  • Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, et al. 2017. Fungal microbiota dysbiosis in IBD. Gut. 66:1039–1048.
  • Stappenbeck TS, McGovern DPB. 2016. Paneth cell alterations in the development and phenotype of Crohn’s disease. Gastroenterology. 152:322–326.
  • Starr AE, Deeke SA, Ning Z, Chiang CK, Zhang X, Mottawea W, Singleton R, Benchimol EI, Wen M, Mack DR, et al. 2017. Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn’s disease from UC. Gut. 66:1573–1583.
  • Stasi LCD, Costa C ARA, Witaicenis A. 2015. Products for the treatment of inflammatory bowel disease: a patent review (2013-2014). Expert Opin Ther Pat. 25:629–642.
  • Sturm A, de Souza HSP, Fiocchi C. 2008. Mucosal T cell proliferation and apoptosis in inflammatory bowel disease. Curr Drug Targets. 9:381–387.
  • Stylianou E. 2018. Recent advances in the etiopathogenesis of inflammatory bowel disease: the role of omics. Mol Diagn Ther. 22:11–23.
  • Summers RW, Elliott DE, Urban JF, Thompson RA, Weinstock JV Jr. 2005. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 128:825–832.
  • Sun M, He C, Cong Y, Liu Z. 2015. Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal Immunol. 8:969–978.
  • Taman H, Fenton CG, Hensel IV, Anderssen E, Florholmen J, Paulssen RH. 2018. Genome-wide DNA methylation in treatment-naïve ulcerative colitis. J Crohns Colitis. 12:1338–1347.
  • Theiss AL, Vijay-Kumar M, Obertone TS, Jones DP, Hansen JM, Gewirtz AT, Merlin D, Sitaraman SV. 2009. Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. Gastroenterology. 137:199–208.
  • Tian T, Wang Z, Zhang J. 2017. Pathomechanisms of oxidative stress in inflammatory bowel disease and potential antioxidant therapies. Oxid Med Cell Longev. 2017:4535194.
  • Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. 2015. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives. World J Gastroenterol. 21:21–46.
  • Torres J, Danese S, Colombel JF. 2013. New therapeutic avenues in ulcerative colitis: thinking out of the box. Gut. 62:1642–1652.
  • Torres J, Burisch J, Riddle M, Dubinsky M, Colombel JF. 2016. Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities. Gut. 65:1061–1069.
  • Turer E, McAlpine W, Wang KW, Lu T, Li X, Tang M, Zhan X, Wang T, Zhan X, Bu CH, et al. 2017. Creatine maintains intestinal homeostasis and protects against colitis. Proc Natl Acad Sci U S A. 114:E1273–E1281.
  • Uhlig HH, Muise AM. 2017. Clinical genomics in inflammatory bowel disease. Trends Genet. 33:629–641.
  • Vatn MH, Sandvik AK. 2015. Inflammatory bowel disease. Scand J Gastroenterol. 50:748–762.
  • Ventura M, O'Flaherty S, Claesson MJ, Turroni F, Klaenhammer TR, van Sinderen D, O'Toole PW. 2009. Genome-scale analyses of health-promoting bacteria: probiogenomics. Nat Rev Microbiol. 7:61–71.
  • Wallace JL. 2008. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev. 88:1547–1565.
  • Wallace KL, Zheng LB, Kanazawa Y, Shih DQ. 2014. Immunopathology of inflammatory bowel disease. World J Gastroenterol. 20:6–21.
  • Wang Y, Tang H, Holmes E, Lindon JC, Turini ME, Sprenger N, Bergonzelli G, Fay LB, Kochhar S, Nicholson JK. 2005. Biochemical characterization of rat intestine development using high-resolution magic-angle-spinning 1H NMR spectroscopy and multivariate data analysis. J Proteome Res. 4:1324–1329.
  • Wang ZK, Yang YS, Chen Y, Yuan J, Sun G, Peng LH. 2014. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease. World J Gastroenterol. 20:14805–14820.
  • Weinstock JV, Elliott DE. 2013. Translatability of helminth therapy in inflammatory bowel diseases. Int J Parasitol. 43:245–251.
  • Yadav DP, Kedia S, Madhusudhan KS, Bopanna S, Goyal S, Jain S, Vikram NK, Sharma R, Makharia GK, Ahuja V. 2017. Body composition in Crohn’s disease and ulcerative colitis: correlation with disease severity and duration. Can J Gastroenterol Hepatol. 2017:1215035.
  • Yoo JY, Groer M, Dutra SVO, Sarkar A, McSkimming DI. 2020. Gut microbiota and immune system interactions. Microorganisms. 8:1587.
  • Zeng MY, Cisalpino D, Varadarajan S, Hellman J, Warren HS, Cascalho M, Inohara N, Núñez G. 2016. Gut microbiota-induced immunoglobulin G controls systemic infection by symbiotic bacteria and pathogens. Immunity. 44:647–658.
  • Zhang X, Chen W, Ning Z, Mayne J, Mack D, Stintzi A, Tian R, Figeys D. 2017. Deep metaproteomics approach for the study of human microbiomes. Anal Chem. 89:9407–9415.
  • Zhang X, Deeke SA, Ning Z, Starr AE, Butcher J, Li J, Mayne J, Cheng K, Liao B, Li L, et al. 2018. Metaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease. Nat Commun. 9:2873.
  • Zhao M, Burisch J. 2019. Impact of genes and the environment on the pathogenesis and disease course of inflammatory bowel disease. Dig Dis Sci. 64:1759–1769.
  • Zoetendal EG, Akkermans ADL, Vliet WMA, de Visser AGM, de Vos WM. 2001. The host genotype affects the bacterial community in the human gastrointestinal tract. Microb Ecol Health Dis. 13:129–134.

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