Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis

References

• Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology. 2017;152(2):327–339.e4. doi:10.1053/j.gastro.2016.10.012.
   PubMed Web of Science ®Google Scholar
• Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020;578(7796):527–21. doi:10.1038/s41586-020-2025-2.
   PubMed Web of Science ®Google Scholar
• de Lange KM, Moutsianas L, Lee JC, de Lange KM, Lamb CA, Luo Y, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet. 2017;49(2):256–261. doi:10.1038/ng.3760.
   PubMed Web of Science ®Google Scholar
• Kuenzig ME, Fung SG, Marderfeld L, Mak JWY, Kaplan GG, Ng SC, Wilson DC, Cameron F, Henderson P, Kotze PG. et al. Twenty-first century trends in the global epidemiology of pediatric-onset inflammatory bowel disease: systematic review. Gastroenterology. 2022;162(4):1147–1159.e4. doi:10.1053/j.gastro.2021.12.282.
   PubMed Web of Science ®Google Scholar
• Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126(6):1620–1633. doi:10.1053/j.gastro.2004.03.024.
   PubMed Web of Science ®Google Scholar
• D’Haens GR, Geboes K, Peeters M. et al. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114:262–267. doi:10.1016/S0016-5085(98)70476-7.
   PubMed Web of Science ®Google Scholar
• Dianda L, Hanby AM, Wright NA, Sebesteny A, Hayday AC, Owen MJ. T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. Am J Pathol. 1997;150:91–97.
   PubMed Web of Science ®Google Scholar
• Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB. 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. doi:10.1128/IAI.66.11.5224-5231.1998.
   PubMed Web of Science ®Google Scholar
• Veltkamp C, Tonkonogy SL, De Jong YP, Albright C, Grenther WB, Balish E, Terhorst C, Sartor RB. Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tgϵ26 mice. Gastroenterology. 2001;120(4):900–913. doi:10.1053/gast.2001.22547.
   PubMed Web of Science ®Google Scholar
• Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 1994;180(6):2359–2364. doi:10.1084/jem.180.6.2359.
   PubMed Web of Science ®Google Scholar
• Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 2019;4(2):293–305. doi:10.1038/s41564-018-0306-4.
   PubMed Web of Science ®Google Scholar
• Nagao-Kitamoto H, Shreiner AB, Gillilland MG 3rd, Kitamoto S, Ishii C, Hirayama A, Kuffa P, El-Zaatari M, Grasberger H, Seekatz AM. et al. Functional characterization of inflammatory bowel disease–associated gut dysbiosis in gnotobiotic mice. Cell Mol Gastroenterol Hepatol. 2016;2(4):468–481. doi:10.1016/j.jcmgh.2016.02.003.
   PubMed Web of Science ®Google Scholar
• Britton GJ, Contijoch EJ, Mogno I, Vennaro OH, Llewellyn SR, Ng R, Li Z, Mortha A, Merad M, Das A. et al. Microbiotas from humans with Inflammatory Bowel disease Alter the Balance of Gut Th17 and RORγt+ regulatory T cells and exacerbate colitis in mice. Immunity. 2019;50(1):212–224.e4. doi:10.1016/j.immuni.2018.12.015.
   PubMed Web of Science ®Google Scholar
• Du Z, Hudcovic T, Mrazek J, Kozakova H, Srutkova D, Schwarzer M, Tlaskalova-Hogenova H, Kostovcik M, Kverka M. Development of gut inflammation in mice colonized with mucosa-associated bacteria from patients with ulcerative colitis. Gut Pathog. 2015;7(1):32. doi:10.1186/s13099-015-0080-2.
   PubMedGoogle Scholar
• Paik J, Meeker S, Hsu CC, Seamons A, Pershutkina O, Snyder JM, Brabb T, Maggio-Price L. Validation studies for germ-free Smad3 -/-mice as a bio-assay to test the causative role of fecal microbiomes in IBD. Gut Microbes. 2020;11(1):21–31. doi:10.1080/19490976.2019.1611151.
   PubMed Web of Science ®Google Scholar
• Burich A, Hershberg R, Waggie K, Zeng W, Brabb T, Westrich G, Viney JL, Maggio-Price L. Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2001;281(3):G764–78. doi:10.1152/ajpgi.2001.281.3.G764.
   PubMed Web of Science ®Google Scholar
• Yu S, Tong K, Zhao Y, Balasubramanian I, Yap GS, Ferraris RP, Bonder EM, Verzi MP, Gao N. Paneth cell multipotency induced by notch activation following injury. Cell Stem Cell. 2018;23(1):46–59.e5. doi:10.1016/j.stem.2018.05.002.
   PubMed Web of Science ®Google Scholar
• Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M. et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6(8):1621–1624. doi:10.1038/ismej.2012.8.
   PubMed Web of Science ®Google Scholar
• Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. doi:10.1038/nmeth.3869.
   PubMed Web of Science ®Google Scholar
• Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive bayesian Classifier for Rapid Assignment of rRNA Sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–5267. doi:10.1128/AEM.00062-07.
   PubMed Web of Science ®Google Scholar
• Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41(D1):D590–6. doi:10.1093/nar/gks1219.
   PubMed Web of Science ®Google Scholar
• Team RC. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2021.
   Google Scholar
• W H. ggplot2: Elegant Graphics for Data Analysis. 2016.
   Google Scholar
• Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi:10.1186/s13059-014-0550-8.
   PubMed Web of Science ®Google Scholar
• Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–2120. doi:10.1093/bioinformatics/btu170.
   PubMed Web of Science ®Google Scholar
• Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9(4):357–359. doi:10.1038/nmeth.1923.
   PubMed Web of Science ®Google Scholar
• Beghini F, McIver LJ, Blanco-Miguez A, Dubois L, Asnicar F, Maharjan S, Mailyan A, Manghi P, Scholz M, Thomas AM. et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife. 2021;10:10. doi:10.7554/eLife.65088.
   Web of Science ®Google Scholar
• Li D, Liu CM, Luo R, Sadakane K, Lam T-W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de bruijn graph. Bioinformatics. 2015;31(10):1674–1676. doi:10.1093/bioinformatics/btv033.
   PubMed Web of Science ®Google Scholar
• Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinf. 2010;11(1):119. doi:10.1186/1471-2105-11-119.
   PubMed Web of Science ®Google Scholar
• Aramaki T, Blanc-Mathieu R, Endo H, Ohkubo K, Kanehisa M, Goto S, Ogata H. KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold. Bioinformatics. 2020;36(7):2251–2252. doi:10.1093/bioinformatics/btz859.
   PubMed Web of Science ®Google Scholar
• Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30(14):2068–2069. doi:10.1093/bioinformatics/btu153.
   PubMed Web of Science ®Google Scholar
• Mistry J, Chuguransky S, Williams L, Qureshi M, Salazar G, Sonnhammer ELL, Tosatto SCE, Paladin L, Raj S, Richardson LJ. et al. Pfam: the protein families database in 2021. Nucleic Acids Res. 2021;49(D1):D412–D419. doi:10.1093/nar/gkaa913.
   PubMed Web of Science ®Google Scholar
• Gish W, States DJ. Identification of protein coding regions by database similarity search. Nat Genet. 1993;3(3):266–272. doi:10.1038/ng0393-266.
   PubMed Web of Science ®Google Scholar
• Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL. NCBI BLAST: a better web interface. Nucleic Acids Res. 2008;36(Web Server):W5–9. doi:10.1093/nar/gkn201.
   PubMed Web of Science ®Google Scholar
• Sayers EW, Beck J, Brister JR, Bolton EE, Canese K, Comeau DC, Funk K, Ketter A, Kim S, Kimchi A. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2020;48(D1):D9–D16. doi:10.1093/nar/gkz899.
   PubMed Web of Science ®Google Scholar
• Kubota H, Sakai T, Gawad A, Makino H, Akiyama T, Ishikawa E, Oishi K. Development of TaqMan-based quantitative PCR for sensitive and selective detection of toxigenic Clostridium difficile in human stools. PloS One. 2014;9(10):e111684. doi:10.1371/journal.pone.0111684.
   PubMed Web of Science ®Google Scholar
• Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15–21. doi:10.1093/bioinformatics/bts635.
   PubMed Web of Science ®Google Scholar
• Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–273. doi:10.1038/ng1180.
   PubMed Web of Science ®Google Scholar
• Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–15550. doi:10.1073/pnas.0506580102.
   PubMed Web of Science ®Google Scholar
• Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, Caprilli R, Colombel J-F, Gasche C, Geboes K. et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(Suppl A):5A–36A. doi:10.1155/2005/269076.
   PubMed Web of Science ®Google Scholar
• Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, Järnerot G, Tysk C, Jansson JK, Engstrand L. et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 2010;139(6):1844–1854.e1. doi:10.1053/j.gastro.2010.08.049.
   PubMed Web of Science ®Google Scholar
• Joossens M, Huys G, Cnockaert M. et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut. 2011;60:631–637. doi:10.1136/gut.2010.223263.
   PubMed Web of Science ®Google Scholar
• Hall AB, Yassour M, Sauk J, Garner A, Jiang X, Arthur T, Lagoudas GK, Vatanen T, Fornelos N, Wilson R. et al. A novel ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 2017;9(1):103. doi:10.1186/s13073-017-0490-5.
   PubMedGoogle Scholar
• Nishino K, Nishida A, Inoue R, Kawada Y, Ohno M, Sakai S, Inatomi O, Bamba S, Sugimoto M, Kawahara M. et al. Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease. J Gastroenterol. 2018;53(1):95–106. doi:10.1007/s00535-017-1384-4.
   PubMed Web of Science ®Google Scholar
• Png CW, Linden SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA, Florin THJ. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105(11):2420–2428. doi:10.1038/ajg.2010.281.
   PubMed Web of Science ®Google Scholar
• Peeters T, Vantrappen G. The paneth cell: a source of intestinal lysozyme. Gut. 1975;16(7):553–558. doi:10.1136/gut.16.7.553.
   PubMed Web of Science ®Google Scholar
• Bel S, Pendse M, Wang Y, Li Y, Ruhn KA, Hassell B, Leal T, Winter SE, Xavier RJ, Hooper LV. et al. Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine. Science. 2017;357(6355):1047–1052. doi:10.1126/science.aal4677.
   PubMed Web of Science ®Google Scholar
• Yu S, Balasubramanian I, Laubitz D, Tong K, Bandyopadhyay S, Lin X, Flores J, Singh R, Liu Y, Macazana C. et al. Paneth cell-derived lysozyme defines the composition of mucolytic microbiota and the inflammatory tone of the intestine. Immunity. 2020;53(2):398–416.e8. doi:10.1016/j.immuni.2020.07.010.
   PubMed Web of Science ®Google Scholar
• Ayabe T, Satchell DP, Pesendorfer P, Tanabe H, Wilson CL, Hagen SJ, Ouellette AJ. Activation of paneth cell α-defensins in mouse small intestine. J Biol Chem. 2002;277(7):5219–5228. doi:10.1074/jbc.M109410200.
   PubMed Web of Science ®Google Scholar
• Weeks CS, Tanabe H, Cummings JE, Crampton SP, Sheynis T, Jelinek R, Vanderlick TK, Cocco MJ, Ouellette AJ. Matrix metalloproteinase-7 activation of mouse paneth cell pro-α-defensins. J Biol Chem. 2006;281(39):28932–28942. doi:10.1074/jbc.M602041200.
   PubMed Web of Science ®Google Scholar
• Mastroianni JR, Costales JK, Zaksheske J, Selsted ME, Salzman NH, Ouellette AJ. Alternative luminal activation mechanisms for paneth cell α-defensins. J Biol Chem. 2012;287(14):11205–11212. doi:10.1074/jbc.M111.333559.
   PubMed Web of Science ®Google Scholar
• Haber AL, Biton M, Rogel N, Herbst RH, Shekhar K, Smillie C, Burgin G, Delorey TM, Howitt MR, Katz Y. et al. A single-cell survey of the small intestinal epithelium. Nature. 2017;551(7680):333–339. doi:10.1038/nature24489.
   PubMed Web of Science ®Google Scholar
• Van Kruiningen HJ, Colombel JF. The forgotten role of lymphangitis in Crohn’s disease. Gut. 2008;57:1–4. doi:10.1136/gut.2007.123166.
   PubMedGoogle Scholar
• Sura R, Colombel JF, Van Kruiningen HJ. Lymphatics, tertiary lymphoid organs and the granulomas of Crohn’s disease: an immunohistochemical study. Aliment Pharmacol Ther. 2011;33(8):930–939. doi:10.1111/j.1365-2036.2011.04605.x.
   PubMed Web of Science ®Google Scholar
• Lochner M, Ohnmacht C, Presley L, Bruhns P, Si-Tahar M, Sawa S, Eberl G. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells. J Exp Med. 2011;208(1):125–134. doi:10.1084/jem.20100052.
   PubMed Web of Science ®Google Scholar
• Parikh K, Antanaviciute A, Fawkner-Corbett D, Jagielowicz M, Aulicino A, Lagerholm C, Davis S, Kinchen J, Chen HH, Alham NK. et al. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 2019;567(7746):49–55. doi:10.1038/s41586-019-0992-y.
   PubMed Web of Science ®Google Scholar
• Lawrance IC, Fiocchi C, Chakravarti S. Ulcerative colitis and Crohn’s disease: distinctive gene expression profiles and novel susceptibility candidate genes. Human Molecular Genetics. 2001;10(5):445–456. doi:10.1093/hmg/10.5.445.
   PubMed Web of Science ®Google Scholar
• Farr L, Ghosh S, Jiang N, Watanabe K, Parlak M, Bucala R, Moonah S. CD74 signaling links inflammation to intestinal epithelial cell regeneration and promotes mucosal healing. Cell Mol Gastroenterol Hepatol. 2020;10(1):101–112. doi:10.1016/j.jcmgh.2020.01.009.
   PubMed Web of Science ®Google Scholar
• Borghese F, Clanchy FI. CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease. Expert Opin Ther Targets. 2011;15(3):237–251. doi:10.1517/14728222.2011.550879.
   PubMed Web of Science ®Google Scholar
• Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. et al. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197(11):1467–1476. doi:10.1084/jem.20030286.
   PubMed Web of Science ®Google Scholar
• Maharshak N. et al. CD74 is a survival receptor on colon epithelial cells. World J Gastroenterol. 2010;16(26):3258–3266. doi:10.3748/wjg.v16.i26.3258.
   PubMed Web of Science ®Google Scholar
• Wang Z, Hu J, Fan R, Zhou J, Zhong J. Association between CD14 gene C-260T polymorphism and inflammatory bowel disease: a meta-analysis. PloS One. 2012;7(9):e45144. doi:10.1371/journal.pone.0045144.
   PubMed Web of Science ®Google Scholar
• Buchheister S, Buettner M, Basic M, Noack A, Breves G, Buchen B, Keubler LM, Becker C, Bleich A. CD14 plays a protective role in experimental inflammatory bowel disease by enhancing intestinal barrier function. Am J Pathol. 2017;187(5):1106–1120. doi:10.1016/j.ajpath.2017.01.012.
   PubMed Web of Science ®Google Scholar
• Masaki T, Matsuoka H, Sugiyama M, Abe N, Goto A, Sakamoto A, Atomi Y. Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer. 2001;84(10):1317–1321. doi:10.1054/bjoc.2001.1790.
   PubMed Web of Science ®Google Scholar
• Sun DW, Zhang YY, Qi Y, Zhou X-T, Lv G-Y. Prognostic significance of MMP-7 expression in colorectal cancer: a meta-analysis. Cancer Epidemiol. 2015;39(2):135–142. doi:10.1016/j.canep.2015.01.009.
   PubMed Web of Science ®Google Scholar
• Rath T, Roderfeld M, Halwe JM, Tschuschner A, Roeb E, Graf J. Cellular sources of MMP-7, MMP-13 and MMP-28 in ulcerative colitis. Scand J Gastroenterol. 2010;45(10):1186–1196. doi:10.3109/00365521.2010.499961.
   PubMed Web of Science ®Google Scholar
• Almohazey D, Lo YH, Vossler CV, Simmons AJ, Hsieh JJ, Bucar EB, Schumacher MA, Hamilton KE, Lau KS, Shroyer NF. et al. The ErbB3 receptor tyrosine kinase negatively regulates paneth cells by PI3K-dependent suppression of Atoh1. Cell Death Differ. 2017;24(5):855–865. doi:10.1038/cdd.2017.27.
   PubMed Web of Science ®Google Scholar
• Gao S, Yan L, Wang R, Li J, Yong J, Zhou X, Wei Y, Wu X, Wang X, Fan X. et al. Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat Cell Biol. 2018;20(6):721–734. doi:10.1038/s41556-018-0105-4.
   PubMed Web of Science ®Google Scholar
• Franzen O, Gan LM, Bjorkegren JLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford). 2019;2019. doi:10.1093/database/baz046.
   PubMed Web of Science ®Google Scholar
• Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102(31):11070–11075. doi:10.1073/pnas.0504978102.
   PubMed Web of Science ®Google Scholar
• Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A. 2019;116(26):12672–12677. doi:10.1073/pnas.1904099116.
   PubMed Web of Science ®Google Scholar
• Togo AH, Khelaifia S, Bittar F, Maraninchi M, Raoult D, Million M. ‘Eisenbergiella massiliensis’, a new species isolated from human stool collected after bariatric surgery. New Microbes New Infect. 2016;13:15–16. doi:10.1016/j.nmni.2016.05.015.
   PubMedGoogle Scholar
• Qin N, Zheng B, Yao J, Guo L, Zuo J, Wu L, Zhou J, Liu L, Guo J, Ni S. et al. Influence of H7N9 virus infection and associated treatment on human gut microbiota. Sci Rep. 2015;5(1):14771. doi:10.1038/srep14771.
   PubMedGoogle Scholar
• Hall IOTE. Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, bacillus difficilis. Am J Dis Child. 1935;49(2):390. doi:10.1001/archpedi.1935.01970020105010.
   Google Scholar
• Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2(1):16020. doi:10.1038/nrdp.2016.20.
   PubMedGoogle Scholar
• Boeriu A, Roman A, Fofiu C, Dobru D. The Current knowledge on clostridioides difficile infection in patients with inflammatory bowel diseases. Pathogens. 2022;11(7):11. doi:10.3390/pathogens11070819.
   Web of Science ®Google Scholar
• Zhou F, Hamza T, Fleur AS, Zhang Y, Yu H, Chen K, Heath JE, Chen Y, Huang H, Feng H. et al. Mice with inflammatory bowel disease are susceptible to clostridium difficile infection with severe disease outcomes. Inflamm Bowel Dis. 2018;24(3):573–582. doi:10.1093/ibd/izx059.
   PubMed Web of Science ®Google Scholar
• Nagao-Kitamoto H, Leslie JL, Kitamoto S, Jin C, Thomsson KA, Gillilland MG, Kuffa P, Goto Y, Jenq RR, Ishii C. et al. Interleukin-22-mediated host glycosylation prevents clostridioides difficile infection by modulating the metabolic activity of the gut microbiota. Nat Med. 2020;26(4):608–617. doi:10.1038/s41591-020-0764-0.
   PubMed Web of Science ®Google Scholar
• Collins J, Auchtung JM, Schaefer L, Eaton KA, Britton RA. Humanized microbiota mice as a model of recurrent Clostridium difficile disease. Microbiome. 2015;3(1):35. doi:10.1186/s40168-015-0097-2.
   PubMed Web of Science ®Google Scholar
• Auchtung JM, Preisner EC, Collins J, Lerma AI, Britton RA. Identification of simplified microbial communities that inhibit clostridioides difficile infection through Dilution/Extinction. mSphere. 2020;5(4). doi:10.1128/mSphere.00387-20.
   PubMed Web of Science ®Google Scholar
• Liu L, Kirst ME, Zhao L, Li E, Wang GP. Microbiome resilience despite a profound loss of minority microbiota following clindamycin challenge in humanized gnotobiotic mice. Microbiol Spectr. 2022;10(1):e0196021. doi:10.1128/spectrum.01960-21.
   PubMed Web of Science ®Google Scholar
• Lesniak NA, Schubert AM, Flynn KJ, Leslie JL, Sinani H, Bergin IL, Young VB, Schloss PD. The gut bacterial community potentiates clostridioides difficile infection severity. mBio. 2022;13(4):e0118322. doi:10.1128/mbio.01183-22.
   PubMed Web of Science ®Google Scholar
• El Feghaly RE, Stauber JL, Deych E, Gonzalez C, Tarr PI, Haslam DB. Markers of intestinal inflammation, not bacterial burden, correlate with clinical outcomes in clostridium difficile infection. Clin Infect Dis. 2013;56(12):1713–1721. doi:10.1093/cid/cit147.
   PubMed Web of Science ®Google Scholar
• AbdelKhalek A, Narayanan SK. Comparison between symptomatic and asymptomatic mice after clostridioides difficile infection reveals novel inflammatory pathways and contributing microbiota. Microorganisms. 2022;10(12):10. doi:10.3390/microorganisms10122380.
   Web of Science ®Google Scholar
• Daquigan N, Seekatz AM, Greathouse KL, Young VB, White JR. High-resolution profiling of the gut microbiome reveals the extent of Clostridium difficile burden. npj Biofilms Microbiomes. 2017;3(1):35. doi:10.1038/s41522-017-0043-0.
   PubMedGoogle Scholar
• Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC. Regulation of Intestinal α-Defensin Activation by the metalloproteinase matrilysin in innate Host defense. Science. 1999;286(5437):113–117. doi:10.1126/science.286.5437.113.
   PubMed Web of Science ®Google Scholar
• Xiao Y, Lian H, Zhong XS, Krishnachaitanya SS, Cong Y, Dashwood RH, Savidge TC, Powell DW, Liu X, Li Q. et al. Matrix metalloproteinase 7 contributes to intestinal barrier dysfunction by degrading tight junction protein claudin-7. Front Immunol. 2022;13:1020902. doi:10.3389/fimmu.2022.1020902.
   PubMed Web of Science ®Google Scholar