Gene–environment interactions shape the host–microbial interface in inflammatory bowel disease

Deal Score0
Deal Score0


  • Rudbaek, J. J. et al. Deciphering the different phases of preclinical inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 21, 86–100 (2023).

  • Ramanan, D. & Cadwell, K. Intrinsic defense mechanisms of the intestinal epithelium. Cell Host Microbe 19, 434–441 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chikina, A. & Matic Vignjevic, D. At the right time in the right place: how do luminal gradients position the microbiota along the gut? Cells Dev. 168, 203712 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gu, Y. et al. Immune microniches shape intestinal Treg function. Nature 628, 854–862 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoytema van Konijnenburg, D. P. et al. Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection. Cell 171, 783–794 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Edelblum, K. L. et al. γδ intraepithelial lymphocyte migration limits transepithelial pathogen invasion and systemic disease in mice. Gastroenterology 148, 1417–1426 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Koch, M. A. et al. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Cell 165, 827–841 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bunker, J. J. et al. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A. Immunity 43, 541–553 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vujkovic-Cvijin, I. et al. The systemic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces. Sci. Transl. Med. 14, eabl3927 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Palm, N. W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nagashima, K. et al. Mapping the T cell repertoire to a complex gut bacterial community. Nature 621, 162–170 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sefik, E. et al. Mucosal immunology. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 349, 993–997 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Atarashi, K. et al. TH17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163, 367–380 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sano, T. et al. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector TH17 responses. Cell 164, 324 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xu, M. et al. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554, 373–377 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chai, J. N. et al. Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation. Sci. Immunol. 2, eaal5068 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brodin, P. & Davis, M. M. Human immune system variation. Nat. Rev. Immunol. 17, 21–29 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bakker, O. B. et al. Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses. Nat. Immunol. 19, 776–786 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brodin, P. et al. Variation in the human immune system is largely driven by non-heritable influences. Cell 160, 37–47 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lin, J. D. et al. Rewilding Nod2 and Atg16l1 mutant mice uncovers genetic and environmental contributions to microbial responses and immune cell composition. Cell Host Microbe 27, 830–840 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yeung, F. et al. Altered immunity of laboratory mice in the natural environment is associated with fungal colonization. Cell Host Microbe 27, 809–822 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carr, E. J. et al. The cellular composition of the human immune system is shaped by age and cohabitation. Nat. Immunol. 17, 461–468 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Patin, E. et al. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nat. Immunol. 19, 302–314 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Saint-Andre, V. et al. Smoking changes adaptive immunity with persistent effects. Nature 626, 827–835 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cader, M. Z. et al. FAMIN is a multifunctional purine enzyme enabling the purine nucleotide cycle. Cell 180, 278–295 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Oyesola, O. et al. Genetic and environmental interactions contribute to immune variation in rewilded mice. Nat. Immunol. 25, 1270–1282 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, H. B., de la Morena, M. T. & Suskind, D. L. The growing need to understand very early onset inflammatory bowel disease. Front Immunol. 12, 675186 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bolton, C. et al. An integrated taxonomy for monogenic inflammatory bowel disease. Gastroenterology 162, 859–876 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sazonovs, A. et al. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility. Nat. Genet. 54, 1275–1283 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stankey, C. T. et al. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature 630, 447–456 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Keestra-Gounder, A. M. et al. NOD1 and NOD2 signalling links ER stress with inflammation. Nature 532, 394–397 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lupfer, C. et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat. Immunol. 14, 480–488 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl Acad. Sci. USA 106, 15813–15818 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Couturier-Maillard, A. et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Invest. 123, 700–711 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Caruso, R. et al. A specific gene–microbe interaction drives the development of Crohn’s disease-like colitis in mice. Sci. Immunol. 4, eaaw4341 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goethel, A. et al. Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure. Mucosal Immunol. 12, 720–732 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ramanan, D., Tang, M. S., Bowcutt, R., Loke, P. & Cadwell, K. Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus. Immunity 41, 311–324 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nayar, S. et al. A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease. Nature 593, 275–281 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, Y. G. et al. The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes. Immunity 34, 769–780 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramanan, D. et al. Helminth infection promotes colonization resistance via type 2 immunity. Science 352, 608–612 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hugot, J. P. et al. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am. J. Gastroenterol. 102, 1259–1267 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jang, K. K. et al. Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization. Cell Host Microbe 31, 1450–1468 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, L. et al. Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2. Nature 568, 405–409 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, J. et al. Gut microbial DL-endopeptidase alleviates Crohn’s disease via the NOD2 pathway. Cell Host Microbe 30, 1435–1449 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Travassos, L. H. et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11, 55–62 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cooney, R. et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16, 90–97 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matsuzawa-Ishimoto, Y., Hwang, S. & Cadwell, K. Autophagy and inflammation. Annu. Rev. Immunol. 36, 73–101 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chu, H. et al. Gene–microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352, 1116–1120 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marchiando, A. M. et al. A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection. Cell Host Microbe 14, 216–224 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Martin, P. K. et al. Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota. Nat. Microbiol. 3, 1131–1141 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saitoh, T. et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 456, 264–268 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lahiri, A., Hedl, M. & Abraham, C. MTMR3 risk allele enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation. Proc. Natl Acad. Sci. USA 112, 10461–10466 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cadwell, K. et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259–263 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsuzawa-Ishimoto, Y. et al. Autophagy protein ATG16L1 prevents necroptosis in the intestinal epithelium. J. Exp. Med. 214, 3687–3705 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsuzawa-Ishimoto, Y. et al. An intestinal organoid-based platform that recreates susceptibility to T cell-mediated tissue injury. Blood 135, 2388–2401 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cadwell, K. et al. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141, 1135–1145 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bel, S. et al. Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine. Science 357, 1047–1052 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Burger, E. et al. Loss of Paneth cell autophagy causes acute susceptibility to Toxoplasma gondii-mediated inflammation. Cell Host Microbe 23, 177–190 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Adolph, T. E. et al. Paneth cells as a site of origin for intestinal inflammation. Nature 503, 272–276 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaser, A. et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743–756 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, T. C. et al. Interaction between smoking and ATG16L1T300A triggers Paneth cell defects in Crohn’s disease. J. Clin. Invest. 128, 5110–5122 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Neil, J. A. et al. IFN-I and IL-22 mediate protective effects of intestinal viral infection. Nat. Microbiol. 4, 1737–1749 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kernbauer, E., Ding, Y. & Cadwell, K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 516, 94–98 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsuzawa-Ishimoto, Y. et al. The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death. Nature 610, 547–554 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, W. et al. Dysregulation of gammadelta intraepithelial lymphocytes precedes Crohn’s disease-like ileitis. Sci. Immunol. 10, eadk7429 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dart, R. J. et al. Conserved gammadelta T cell selection by BTNL proteins limits progression of human inflammatory bowel disease. Science 381, eadh0301 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jaeger, N. et al. Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions. Nat. Commun. 12, 1921 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, L. et al. Type I interferons link viral infection to enhanced epithelial turnover and repair. Cell Host Microbe 17, 85–97 (2014).

  • Mehto, S. et al. The Crohn’s disease risk factor IRGM limits NLRP3 inflammasome activation by impeding its assembly and by mediating its selective autophagy. Mol. Cell 73, 429–445 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Doron, I. et al. Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies. Cell 184, 1017–1031 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lamas, B. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22, 598–605 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Q. et al. Commensal bacteria direct selective cargo sorting to promote symbiosis. Nat. Immunol. 16, 918–926 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun, S. et al. Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction. Sci. Immunol. 9, eadi7907 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tasegian, A. et al. LRRK2 is not required for lysozyme expression in Paneth cells. Nat. Immunol. 25, 2037–2039 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hedl, M., Zheng, S. & Abraham, C. The IL18RAP region disease polymorphism decreases IL-18RAP/IL-18R1/IL-1R1 expression and signaling through innate receptor-initiated pathways. J. Immunol. 192, 5924–5932 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Taylor, G. A. et al. Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium. PLoS Pathog. 16, e1008553 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jarret, A. et al. Enteric nervous system-derived IL-18 orchestrates mucosal barrier immunity. Cell 180, 50–63 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shouval, D. S. et al. Interleukin 1beta mediates intestinal inflammation in mice and patients with interleukin 10 receptor deficiency. Gastroenterology 151, 1100–1104 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shouval, D. S. et al. Enhanced TH17 responses in patients with IL10 receptor deficiency and infantile-onset IBD. Inflamm. Bowel Dis. 23, 1950–1961 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Mohanan, V. et al. C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science 359, 1161–1166 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luong, P. et al. INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling. eLife 7, e38539 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rutgeerts, P. et al. Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 338, 771–774 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Britton, G. J. 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 50, 212–224 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ananthakrishnan, A. N., Whelan, K., Allegretti, J. R. & Sokol, H. Diet and microbiome-directed therapy 2.0 for IBD. Clin. Gastroenterol. Hepatol. 23, 406–418 (2024).

  • Peery, A. F. et al. AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases. Gastroenterology 166, 409–434 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aschard, H. et al. Genetic effects on the commensal microbiota in inflammatory bowel disease patients. PLoS Genet. 15, e1008018 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kelly, C. J. et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17, 662–671 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Byndloss, M. X. et al. Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357, 570–575 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Atarashi, K. et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science 358, 359–365 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rojas-Tapias, D. F. et al. Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine. Nat. Microbiol. 7, 1673–1685 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumbhari, A. et al. Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases. Cell Host Microbe 32, 1147–1162 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cao, Y. et al. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 378, eabm3233 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lopez, C. A. et al. Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration. Science 353, 1249–1253 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winter, S. E. et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ladinsky, M. S. et al. Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. Science 363, eaat4042 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lin, X. et al. IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment. Immunity 55, 237–253 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. S. et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity 43, 727–738 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Maxwell, J. R. et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity 43, 739–750 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Song, X. et al. Growth factor FGF2 cooperates with interleukin-17 to repair intestinal epithelial damage. Immunity 43, 488–501 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kumar, P. et al. Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44, 659–671 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693–1700 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Diehl, G. E. et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature 494, 116–120 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, M. et al. Critical role for the microbiota in CX3CR1+ intestinal mononuclear phagocyte regulation of intestinal T cell responses. Immunity 49, 151–163 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ha, C. W. Y. et al. Translocation of viable gut microbiota to mesenteric adipose drives formation of creeping fat in humans. Cell 183, 666–683 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, J. et al. Microbiota-induced alteration of kynurenine metabolism in macrophages drives formation of creeping fat in Crohn’s disease. Cell Host Microbe 32, 1927–1943 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yu, S. et al. Paneth cell-derived lysozyme defines the composition of mucolytic microbiota and the inflammatory tone of the intestine. Immunity 53, 398–416 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Limon, J. J. et al. Malassezia is associated with Crohn’s disease and exacerbates colitis in mouse models. Cell Host Microbe 25, 377–388 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jain, U. et al. Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice. Science 371, 1154–1159 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, X. V. et al. Immune regulation by fungal strain diversity in inflammatory bowel disease. Nature 603, 672–678 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ost, K. S. et al. Adaptive immunity induces mutualism between commensal eukaryotes. Nature 596, 114–118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savage, H. P. et al. Epithelial hypoxia maintains colonization resistance against Candida albicans. Cell Host Microbe 32, 1103–1113 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Howitt, M. R. et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351, 1329–1333 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gerrick, E. R. et al. Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition. Cell 187, 62–78 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chudnovskiy, A. et al. Host–protozoan interactions protect from mucosal infections through activation of the inflammasome. Cell 167, 444–456 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dallari, S. et al. Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome. Cell Host Microbe 29, 1014–1029 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, J. Y. et al. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-beta production. Immunity 44, 889–900 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Boland, B. S. et al. Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses. Sci. Immunol. 5, eabb4432 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uzzan, M. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Nat. Med. 28, 766–779 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hand, T. W. et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science 337, 1553–1556 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alexander, K. L. et al. Human microbiota flagellins drive adaptive immune responses in Crohn’s disease. Gastroenterology 161, 522–535 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pedersen, T. K. et al. The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn’s disease. Immunity 55, 1909–1923 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Martini, G. R. et al. Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease. Nat. Med. 29, 2602–2614 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fonseca, D. M. et al. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell 163, 354–366 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Czepielewski, R. S. et al. Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor. Immunity 54, 2795–2811 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carmody, R. N., Varady, K. & Turnbaugh, P. J. Digesting the complex metabolic effects of diet on the host and microbiome. Cell 187, 3857–3876 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Link, V. M. et al. Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans. Nat. Med. 30, 560–572 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hashash, J. G., Elkins, J., Lewis, J. D. & Binion, D. G. AGA clinical practice update on diet and nutritional therapies in patients with inflammatory bowel disease: expert review. Gastroenterology 166, 521–532 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pereira, G. V. et al. Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host. Cell Host Microbe 32, 527–542 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 92–96 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wegorzewska, M. M. et al. Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen. Sci. Immunol. 4, eaau9079 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lei, C. et al. Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice. Nat. Microbiol. 10, 126–143 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rausch, P. et al. Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc. Natl Acad. Sci. USA 108, 19030–19035 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kamioka, M. et al. Intestinal commensal microbiota and cytokines regulate Fut2+ Paneth cells for gut defense. Proc. Natl Acad. Sci. USA 119, e2115230119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104–108 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, T. C. et al. Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation. Cell Host Microbe 29, 988–1001 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hang, S. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576, 143–148 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paik, D. et al. Human gut bacteria produce TH17-modulating bile acid metabolites. Nature 603, 907–912 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Song, X. et al. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature 577, 410–415 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, J. Y. et al. High-fat diet and antibiotics cooperatively impair mitochondrial bioenergetics to trigger dysbiosis that exacerbates pre-inflammatory bowel disease. Cell Host Microbe 28, 273–284 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Culp, E. J., Nelson, N. T., Verdegaal, A. A. & Goodman, A. L. Microbial transformation of dietary xenobiotics shapes gut microbiome composition. Cell 187, 6327–6345 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sanmarco, L. M. et al. Identification of environmental factors that promote intestinal inflammation. Nature 611, 801–809 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barnes, E. L., Loftus, E. V. Jr. & Kappelman, M. D. Effects of race and ethnicity on diagnosis and management of inflammatory bowel diseases. Gastroenterology 160, 677–689 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Khalessi, A. et al. Differential manifestations of inflammatory bowel disease based on race and immigration status. Gastro Hep. Adv. 3, 326–332 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Liu, Z. et al. Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. Nat. Genet. 55, 796–806 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gettler, K. et al. Common and rare variant prediction and penetrance of IBD in a large, multi-ethnic, health system-based biobank cohort. Gastroenterology 160, 1546–1557 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Astore, C. et al. The role of admixture in the rare variant contribution to inflammatory bowel disease. Genome Med. 15, 97 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Misra, R., Faiz, O., Munkholm, P., Burisch, J. & Arebi, N. Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups. World J. Gastroenterol. 24, 424–437 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Damas, O. M. et al. Inflammatory bowel disease is presenting sooner after immigration in more recent US immigrants from Cuba. Aliment. Pharm. Ther. 46, 303–309 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Ip, W. K. E., Hoshi, N., Shouval, D. S., Snapper, S. & Medzhitov, R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356, 513–519 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torres, J. et al. Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis. Gastroenterology 159, 96–104 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Axelrad, J. E., Cadwell, K. H., Colombel, J. F. & Shah, S. C. Systematic review: gastrointestinal infection and incident inflammatory bowel disease. Aliment. Pharm. Ther. 51, 1222–1232 (2020).

    Article 

    Google Scholar
     

  • Axelrad, J. E. et al. Gastrointestinal infection increases odds of inflammatory bowel disease in a nationwide case–control study. Clin. Gastroenterol. Hepatol. 17, 1311–1322 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Galipeau, H. J. et al. Novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis. Gastroenterology 160, 1532–1545 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nandy, A. et al. Epstein–Barr Virus (EBV) exposure precedes cCrohn’s disease development. Gastroenterology (2025).

  • Lee, J. C. et al. Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn’s disease. Nat. Genet. 49, 262–268 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kugathasan, S. et al. Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet 389, 1710–1718 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schett, G., McInnes, I. B. & Neurath, M. F. Reframing immune-mediated inflammatory diseases through signature cytokine hubs. N. Engl. J. Med. 385, 628–639 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Canales-Herrerias, P. et al. Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis. Sci. Immunol. 9, eadg7549 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Canale, V. et al. PTPN2 is a critical regulator of ileal paneth cell viability and function in mice. Cell Mol. Gastroenterol. Hepatol. 16, 39–62 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bamias, G., Menghini, P., Pizarro, T. T. & Cominelli, F. Targeting TL1A and DR3: the new frontier of anti-cytokine therapy in IBD. Gut 74, 652–668 (2024).

  • Castellanos, J. G. et al. Microbiota-induced TNF-like ligand 1A drives group 3 innate lymphoid cell-mediated barrier protection and intestinal T cell activation during colitis. Immunity 49, 1077–1089 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jacob, N. et al. Inflammation-independent TL1A-mediated intestinal fibrosis is dependent on the gut microbiome. Mucosal Immunol. 11, 1466–1476 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jang, K. K. et al. Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness. Gastroenterology 167, 1453–1456 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Khan, M. T. et al. Synergy and oxygen adaptation for development of next-generation probiotics. Nature 620, 381–385 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Broadhurst, M. J. et al. IL-22+ CD4+ T cells are associated with therapeutic Trichuris trichiura infection in an ulcerative colitis patient. Sci. Transl. Med. 2, 60ra88 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maizels, R. M. Regulation of immunity and allergy by helminth parasites. Allergy 75, 524–534 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Federici, S. et al. Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell 185, 2879–2898 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Furuichi, M. et al. Commensal consortia decolonize Enterobacteriaceae via ecological control. Nature 633, 878–886 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Talbot, J. et al. Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier. Nature 579, 575–580 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Friedrich, M. et al. IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat. Med. 27, 1970–1981 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     



  • Source link

    We will be happy to hear your thoughts

    Leave a reply

    Dupuytren Solutions
    Logo
    Shopping cart