{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:48:37Z","timestamp":1791809317615,"version":"4.3.4"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lymphedema Research and Education Program"},{"name":"Snyder Institute for Chronic Diseases"},{"DOI":"10.13039\/100012866","name":"Cumming School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008459","name":"University of Calgary","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008459","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant-in-Aid from Crohn\u2019s and Colitis Canada","award":["#623941"],"award-info":[{"award-number":["#623941"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>TNF\u03b1 has long stood as a hallmark feature of both inflammatory bowel disease and arthritis with its therapeutic potential demonstrated in neutralizing monoclonal antibody treatments such as Infliximab. Due to the high global burden of latent Mycobacterium tuberculosis (TB) infections, prior to receiving anti-TNF therapy, patients testing positive for latent TB are given prophylactic treatment with anti-tuberculoid medications including the first described TB-selective antibiotic, Isoniazid. While this is common clinical practice to prevent the emergence of TB, little is known about whether Isoniazid modifies intestinal inflammation alone. The aim of this study, therefore, was to determine whether Isoniazid presents a novel TB-independent therapeutic option for the treatment of Crohn\u2019s disease (CD)-like ileitis and uncover new mechanisms predisposing the host to intestinal inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The transgenic TNF\u0394ARE mouse model of Crohn\u2019s-like terminal ileitis was used. The impact of Isoniazid administration (10\u00a0mg\/kg\/day dose in drinking water) on disease development was monitored between 8 and 12 weeks of age using a variety of behavioral and serological assays. Behavioral and motor functions were assessed using the LABORAS automated monitoring system while systemic and local tissue inflammation were determined at experimental termination using multiplex cytokine analysis. Whole-mount tissue immunofluorescence and fluorescent in situ hybridization were used to qualify changes within the host as well as the microbial compartment of the ileum and associated mesentery. Proposed cellular mechanisms of altered cytokine decay were performed on isolated primary splenocytes in vitro using selective pharmacological agents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared to age-matched wild-type littermates, TNF\u0394ARE mice display prominent progressive sickness behaviors from 8 through 12 weeks of age indicated by reduced movement, climbing, and rearing. Prophylactic administration of Isoniazid (10\u00a0mg\/kg\/day) is effectively able to protect TNF\u0394ARE mice from this loss of function during the same period. Analysis revealed that Isoniazid was able to significantly reduce both systemic and intestinal inflammation compared to untreated vehicle controls impacting the epithelial colonization of known pathobiont segmented filamentous bacteria (SFB). Reduction in terminal ileal inflammation was also associated to the diminished formation of precursor-tertiary lymphoid organs within the associated ileal mesentery which were found to be associated with endospores derived SFB itself. Finally, we reveal that due to their genetic manipulation, TNF\u0394ARE mice display accelerated posttranscriptional decay of IL-22 mRNA resulting in diminished IL-22 protein production and associated downstream antimicrobial peptide production.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Isoniazid protects against the development of intestinal and systemic inflammation in the TNF\u0394ARE model of terminal ileitis by limiting the expansion of mucosal SFB and progression of the associated microbial-driven inflammation. This work highlights a possible mycobacterial-independent function of Isoniazid in limiting CD pathophysiology through limiting the mucosal establishment of pathobionts such as SFB and the association of such microbe-derived endospores linked to the formation of ectopic tertiary lymphoid organs seen commonly in patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf032","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T04:39:03Z","timestamp":1740285543000},"source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the therapeutic potential of anti-tuberculoid agent Isoniazid in a model of microbial-driven Crohn\u2019s disease"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0571-4531","authenticated-orcid":false,"given":"Matthew","family":"Stephens","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Keane","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Roizes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Defaye","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Altier","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Yves","family":"von der Weid","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Inflammation Research Network Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary , Calgary, Alberta T2N4N1 ,","place":["Canada"]},{"name":"Snyder Institute for Chronic Diseases, University of Calgary , HS 1665, 3330 Hospital Drive NW, Calgary, Alberta T2N4N1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,23]]},"reference":[{"key":"2025031916354559100_CIT0001","doi-asserted-by":"crossref","first-page":"e065186","DOI":"10.1136\/bmjopen-2022-065186","article-title":"Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019","volume":"13","author":"Wang","year":"2023","journal-title":"BMJ Open"},{"key":"2025031916354559100_CIT0002","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1053\/j.gastro.2023.07.003","article-title":"Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States","volume":"165","author":"Lewis","year":"2023","journal-title":"Gastroenterology."},{"key":"2025031916354559100_CIT0003","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1172\/JCI39143","article-title":"Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism revealed","volume":"119","author":"Miller","year":"2009","journal-title":"J Clin Invest."},{"key":"2025031916354559100_CIT0004","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1001\/jama.2023.3954","article-title":"Screening for latent tuberculosis infection in adults: updated evidence report and systematic review for the US Preventive Services Task Force","volume":"329","author":"Jonas","year":"2023","journal-title":"JAMA."},{"key":"2025031916354559100_CIT0005","doi-asserted-by":"crossref","first-page":"e1910960","DOI":"10.1001\/jamanetworkopen.2019.10960","article-title":"Latent tuberculosis infection testing strategies for HIV-positive individuals in Hong Kong","volume":"2","author":"Wong","year":"2019","journal-title":"JAMA Network Open"},{"key":"2025031916354559100_CIT0006","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1186\/s12879-014-0667-0","article-title":"HIV patients with latent tuberculosis living in a low-endemic country do not develop active disease during a 2 year follow-up; a Norwegian prospective multicenter study","volume":"14","author":"Pullar","year":"2014","journal-title":"BMC Infect Dis."},{"key":"2025031916354559100_CIT0007","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/apt.16952","article-title":"Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management","volume":"56","author":"Fehily","year":"2022","journal-title":"Aliment Pharmacol Ther."},{"key":"2025031916354559100_CIT0008","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.3389\/fimmu.2020.02006","article-title":"Diagnosis for latent tuberculosis infection: new alternatives","volume":"11","author":"Carranza","year":"2020","journal-title":"Front Immunol."},{"key":"2025031916354559100_CIT0009","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1056\/NEJMoa011110","article-title":"Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent","volume":"345","author":"Keane","year":"2001","journal-title":"N Engl J Med."},{"key":"2025031916354559100_CIT0010","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/art.20009","article-title":"Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy","volume":"50","author":"Wolfe","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2025031916354559100_CIT0011","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1128\/AAC.39.11.2472","article-title":"Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis","volume":"39","author":"Rouse","year":"1995","journal-title":"Antimicrob Agents Chemother."},{"key":"2025031916354559100_CIT0012","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1128\/AAC.01691-09","article-title":"Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis","volume":"54","author":"Ando","year":"2010","journal-title":"Antimicrob Agents Chemother."},{"key":"2025031916354559100_CIT0013","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1099\/00221287-63-1-41","article-title":"Inhibition by isoniazid of synthesis of mycolic acids in Mycobacterium tuberculosis","volume":"63","author":"Winder","year":"1970","journal-title":"J Gen Microbiol."},{"key":"2025031916354559100_CIT0014","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/AAC.37.10.2251","article-title":"Susceptibilities of oxyR regulon mutants of Escherichia coli and Salmonella typhimurium to isoniazid","volume":"37","author":"Rosner","year":"1993","journal-title":"Antimicrob Agents Chemother."},{"key":"2025031916354559100_CIT0015","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","article-title":"Impaired on\/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity."},{"key":"2025031916354559100_CIT0016","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12865-019-0292-1","article-title":"Tristetraprolin specifically regulates the expression and alternative splicing of immune response genes in HeLa cells","volume":"20","author":"Tu","year":"2019","journal-title":"BMC Immunol."},{"key":"2025031916354559100_CIT0017","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molimm.2007.05.017","article-title":"Tristetraprolin regulates TNF TNF-alpha mRNA stability via a proteasome dependent mechanism involving the combined action of the ERK and p38 pathways","volume":"45","author":"Deleault","year":"2008","journal-title":"Mol Immunol."},{"key":"2025031916354559100_CIT0018","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/ecco-jcc\/jjab222","article-title":"Selective targeting of tumour necrosis factor receptor 1 induces stable protection from Crohn\u2019s-like ileitis in TNF\u0394ARE mice","volume":"16","author":"Chakraborty","year":"2022","journal-title":"J Crohns Colitis."},{"key":"2025031916354559100_CIT0019","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.ajpath.2016.12.007","article-title":"TNFDeltaARE mice display abnormal lymphatics and develop tertiary lymphoid organs in the mesentery","volume":"187","author":"Rehal","year":"2017","journal-title":"Am J Pathol."},{"key":"2025031916354559100_CIT0020","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1016\/j.immuni.2021.10.003","article-title":"Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor","volume":"54","author":"Czepielewski","year":"2021","journal-title":"Immunity."},{"key":"2025031916354559100_CIT0021","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00018-022-04388-x","article-title":"Role of tertiary lymphoid organs in the regulation of immune responses in the periphery","volume":"79","author":"Bery","year":"2022","journal-title":"Cell Mol Life Sci."},{"key":"2025031916354559100_CIT0022","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/mi.2015.102","article-title":"Host and microbiota interactions are critical for development of murine Crohn\u2019s-like ileitis","volume":"9","author":"Roulis","year":"2016","journal-title":"Mucosal Immunol"},{"key":"2025031916354559100_CIT0023","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1136\/gutjnl-2015-309333","article-title":"Dysbiotic gut microbiota causes transmissible Crohn\u2019s disease-like ileitis independent of failure in antimicrobial defence","volume":"65","author":"Schaubeck","year":"2016","journal-title":"Gut."},{"key":"2025031916354559100_CIT0024","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40168-023-01508-y","article-title":"Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn\u2019s disease","volume":"11","author":"Metwaly","year":"2023","journal-title":"Microbiome"},{"key":"2025031916354559100_CIT0025","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1016\/j.cell.2021.07.001","article-title":"The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock","volume":"184","author":"BrooksBehrendt","year":"2021","journal-title":"Cell."},{"key":"2025031916354559100_CIT0026","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0165-0270(03)00227-9","article-title":"LABORAS: initial pharmacological validation of a system allowing continuous monitoring of laboratory rodent behaviour","volume":"130","author":"Quinn","year":"2003","journal-title":"J Neurosci Methods."},{"key":"2025031916354559100_CIT0027","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3389\/fimmu.2019.00557","article-title":"Mesenteric lymphatic alterations observed during DSS induced intestinal inflammation are driven in a TLR4-PAMP\/DAMP discriminative manner","volume":"10","author":"Stephens","year":"2019","journal-title":"Front Immunol."},{"key":"2025031916354559100_CIT0028","doi-asserted-by":"crossref","first-page":"G408","DOI":"10.1152\/ajpgi.00340.2017","article-title":"Acute small intestinal inflammation results in persistent lymphatic alterations","volume":"314","author":"Rehal","year":"2017","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2025031916354559100_CIT0029","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.chom.2011.08.007","article-title":"Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of Th17 cell differentiation","volume":"10","author":"Prakash","year":"2011","journal-title":"Cell Host Microbe."},{"key":"2025031916354559100_CIT0030","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/ismej.2012.128","article-title":"Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens","volume":"7","author":"Yin","year":"2013","journal-title":"ISME J."},{"key":"2025031916354559100_CIT0031","doi-asserted-by":"crossref","first-page":"G87","DOI":"10.1152\/ajpgi.00421.2014","article-title":"TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis","volume":"309","author":"Lapointe","year":"2015","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2025031916354559100_CIT0032","doi-asserted-by":"crossref","first-page":"G1002","DOI":"10.1152\/ajpgi.00005.2013","article-title":"Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice","volume":"304","author":"Cattaruzza","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2025031916354559100_CIT0033","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1523\/JNEUROSCI.1806-12.2013","article-title":"TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic inflammation and pain in chronic pancreatitis","volume":"33","author":"Schwartz","year":"2013","journal-title":"J Neurosci."},{"key":"2025031916354559100_CIT0034","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1007\/s10620-020-06759-5","article-title":"Growth delay in inflammatory bowel diseases: significance, causes, and management","volume":"66","author":"Wong","year":"2021","journal-title":"Dig Dis Sci."},{"key":"2025031916354559100_CIT0035","first-page":"327","article-title":"Management of arthritis in patients with inflammatory bowel disease","volume":"8","author":"Orchard","year":"2012","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"2025031916354559100_CIT0036","doi-asserted-by":"crossref","first-page":"126","DOI":"10.31138\/mjr.33.1.126","article-title":"Inflammatory bowel disease-related spondyloarthritis: the last unexplored territory of rheumatology","volume":"33","author":"Zioga","year":"2022","journal-title":"Mediterr J Rheumatol"},{"key":"2025031916354559100_CIT0037","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.omtn.2022.05.026","article-title":"Mincle-binding DNA aptamer demonstrates therapeutic potential in a model of inflammatory bowel disease","volume":"28","author":"Stephens","year":"2022","journal-title":"Mol Ther Nucleic Acids."},{"key":"2025031916354559100_CIT0038","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.15739","article-title":"The dietary fibre rhamnogalacturonan improves intestinal epithelial barrier function in a microbiota-independent manner","volume":"179","author":"Baggio","year":"2022","journal-title":"Br J Pharmacol."},{"key":"2025031916354559100_CIT0039","doi-asserted-by":"crossref","first-page":"G280","DOI":"10.1152\/ajpgi.00338.2019","article-title":"Nr4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts","volume":"321","author":"Pulakazhi Venu","year":"2021","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2025031916354559100_CIT0040","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of intestinal Th17 cells by segmented filamentous bacteria","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell."},{"key":"2025031916354559100_CIT0041","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1016\/j.ajpath.2016.07.026","article-title":"Lymphoid aggregates remodel lymphatic collecting vessels that serve mesenteric lymph nodes in Crohn\u2019s disease","volume":"186","author":"Randolph","year":"2016","journal-title":"Am J Pathol."},{"key":"2025031916354559100_CIT0042","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.immuni.2014.03.009","article-title":"Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses","volume":"40","author":"L\u00e9cuyer","year":"2014","journal-title":"Immunity."},{"key":"2025031916354559100_CIT0043","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ni.1825","article-title":"Enteric defensins are essential regulators of intestinal microbial ecology","volume":"11","author":"Salzman","year":"2010","journal-title":"Nat Immunol."},{"key":"2025031916354559100_CIT0044","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4161\/19490976.2014.990790","article-title":"Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice","volume":"6","author":"Aguilera","year":"2015","journal-title":"Gut Microbes"},{"key":"2025031916354559100_CIT0045","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/mi.2015.102","article-title":"Host and microbiota interactions are critical for development of murine Crohn\u2019s-like ileitis","volume":"9","author":"Roulis","year":"2016","journal-title":"Mucosal Immunol"},{"key":"2025031916354559100_CIT0046","doi-asserted-by":"crossref","first-page":"1968258","DOI":"10.1080\/19490976.2021.1968258","article-title":"IL-27 induces LL-37\/CRAMP expression from intestinal epithelial cells: implications for immunotherapy of Clostridioides difficile infection","volume":"13","author":"Xu","year":"2021","journal-title":"Gut Microbes"},{"key":"2025031916354559100_CIT0047","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.bbagrm.2013.02.003","article-title":"Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action","volume":"1829","author":"Brooks","year":"2013","journal-title":"Biochim Biophys Acta."},{"key":"2025031916354559100_CIT0048","doi-asserted-by":"crossref","first-page":"15112","DOI":"10.1038\/srep15112","article-title":"Tristetraprolin regulation of interleukin-22 production","volume":"5","author":"H\u00e4rdle","year":"2015","journal-title":"Sci Rep."},{"key":"2025031916354559100_CIT0049","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1261\/rna.5180304","article-title":"Characterization of deadenylation in trypanosome extracts and its inhibition by poly(A)-binding protein Pab1p","volume":"10","author":"Milone","year":"2004","journal-title":"RNA."},{"key":"2025031916354559100_CIT0050","doi-asserted-by":"crossref","first-page":"G421","DOI":"10.1152\/ajpgi.00508.2007","article-title":"Inhibition of tristetraprolin deadenylation by poly(A) binding protein","volume":"295","author":"Rowlett","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol."},{"key":"2025031916354559100_CIT0051","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41577-024-01008-6","article-title":"Strategies for targeting cytokines in inflammatory bowel disease","volume":"24","author":"Neurath","year":"2024","journal-title":"Nat Rev Immunol."},{"key":"2025031916354559100_CIT0052","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1146\/annurev-med-042320-021020","article-title":"The gut microbiome and inflammatory bowel diseases","volume":"73","author":"Shan","year":"2022","journal-title":"Annu Rev Med."},{"key":"2025031916354559100_CIT0053","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41430-021-00991-6","article-title":"Role of the gut microbiome in chronic diseases: a narrative review","volume":"76","author":"Vijay","year":"2022","journal-title":"Eur J Clin Nutr."},{"key":"2025031916354559100_CIT0054","doi-asserted-by":"crossref","first-page":"139127","DOI":"10.1155\/2012\/139127","article-title":"The tuberculous granuloma: an unsuccessful host defence mechanism providing a safety shelter for the bacteria","volume":"2012","author":"Silva Miranda","year":"2012","journal-title":"Clin Dev Immunol."},{"key":"2025031916354559100_CIT0055","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.crohns.2010.02.006","article-title":"Granulomas in Crohn\u2019s disease: are newly discovered genetic variants involved","volume":"4","author":"Mazor","year":"2010","journal-title":"J Crohns Colitis."},{"key":"2025031916354559100_CIT0056","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1093\/ibd\/izae020.126","article-title":"Non-caseating granulomas are associated with stricturing Crohn\u2019s disease and their number and size are increased in the muscularis propria of strictured compared to non-strictured intestingal segments","volume":"30","author":"Massey","year":"2024","journal-title":"Inflamm Bowel Dis."},{"key":"2025031916354559100_CIT0057","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6901a1","article-title":"Guidelines for the treatment of latent tuberculosis infection: recommendations from the national tuberculosis controllers association and CDC, 2020","volume":"69","author":"Sterling","year":"2020","journal-title":"MMWR Recomm Rep."},{"key":"2025031916354559100_CIT0058","first-page":"523","article-title":"A study of the effects of isoniazid on the emotions of tuberculous patients","volume":"68","author":"Lorenz","year":"1953","journal-title":"Am Rev Tuberc"},{"key":"2025031916354559100_CIT0059","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/archneurpsyc.1953.02320330042005","article-title":"Anxiety and depressive states treated with isonicotinyl hydrazide (isoniazid)","volume":"70","author":"Salzer","year":"1953","journal-title":"AMA Arch Neurol Psychiatry"},{"key":"2025031916354559100_CIT0060","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bcp.2016.02.003","article-title":"Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD+ adduct formation: a comparison of the reactivity of isoniazid with its known human metabolites","volume":"106","author":"Khan","year":"2016","journal-title":"Biochem Pharmacol."},{"key":"2025031916354559100_CIT0061","doi-asserted-by":"crossref","first-page":"e4758","DOI":"10.21769\/BioProtoc.4758","article-title":"Measuring myeloperoxidase activity as a marker of inflammation in gut tissue samples of mice and rat","volume":"13","author":"Hanning","year":"2023","journal-title":"Bio Protoc"},{"key":"2025031916354559100_CIT0062","doi-asserted-by":"crossref","first-page":"30190","DOI":"10.1074\/jbc.C114.598946","article-title":"Isoniazid induces apoptosis of activated CD4+ T cells: implications for post-therapy tuberculosis reactivation and reinfection","volume":"289","author":"Tousif","year":"2014","journal-title":"J Biol Chem."},{"key":"2025031916354559100_CIT0063","doi-asserted-by":"crossref","first-page":"107577","DOI":"10.1016\/j.intimp.2021.107577","article-title":"Therapeutic effect of an anti-tuberculosis agent, isoniazid, and its nano-isoform in ulcerative colitis","volume":"96","author":"Yaghoubi","year":"2021","journal-title":"Int Immunopharmacol."},{"key":"2025031916354559100_CIT0064","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3748\/wjg.v22.i3.1078","article-title":"Role of antibiotics for treatment of inflammatory bowel disease","volume":"22","author":"Nitzan","year":"2016","journal-title":"World J Gastroenterol."},{"key":"2025031916354559100_CIT0065","first-page":"1","article-title":"Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin","volume":"74","author":"Buret","year":"2010","journal-title":"Can J Vet Res."},{"key":"2025031916354559100_CIT0066","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/IJGM.S56957","article-title":"Antibiotics for the treatment of rheumatoid arthritis","volume":"7","author":"Ogrendik","year":"2013","journal-title":"Int J Gen Med"},{"key":"2025031916354559100_CIT0067","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3810\/pgm.2014.07.2779","article-title":"Gut microbiota and inflammatory bowel disease: the role of antibiotics in disease management","volume":"126","author":"Kerman","year":"2014","journal-title":"Postgrad Med."},{"key":"2025031916354559100_CIT0068","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/1751-2980.12216","article-title":"Use of antibiotics in patients with Crohn\u2019s disease: a systematic review and meta-analysis","volume":"16","author":"Su","year":"2015","journal-title":"J Dig Dis."},{"key":"2025031916354559100_CIT0069","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.gastro.2023.09.019","article-title":"Pathobionts in inflammatory bowel disease: origins, underlying mechanisms, and implications for clinical care","volume":"166","author":"Gilliland","year":"2024","journal-title":"Gastroenterology."},{"key":"2025031916354559100_CIT0070","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41564-019-0608-1","article-title":"Intracellular offspring released from SFB filaments are flagellated","volume":"5","author":"Nkamba","year":"2020","journal-title":"Nat Microbiol."},{"key":"2025031916354559100_CIT0071","doi-asserted-by":"publisher","first-page":"e00128","DOI":"10.1128\/jb.00128-18","article-title":"Reduce, induce, thrive: bacterial redox sensing during pathogenesis","volume":"200","author":"Reniere Michelle","year":"2018","journal-title":"J Bacteriol."},{"key":"2025031916354559100_CIT0072","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1038\/s41396-018-0192-z","article-title":"Endospores and other lysis-resistant bacteria comprise a widely shared core community within the human microbiota","volume":"12","author":"Kearney","year":"2018","journal-title":"ISME J."},{"key":"2025031916354559100_CIT0073","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1128\/MMBR.64.3.548-572.2000","article-title":"Resistance of Bacillus endospores to extreme terrestrial and extraterrestrial environments","volume":"64","author":"Nicholson","year":"2000","journal-title":"Microbiol Mol Biol Rev."},{"key":"2025031916354559100_CIT0074","doi-asserted-by":"crossref","first-page":"e163591","DOI":"10.1172\/JCI163591","article-title":"Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis","volume":"133","author":"Reyes","year":"2023","journal-title":"J Clin Invest."},{"key":"2025031916354559100_CIT0075","doi-asserted-by":"crossref","first-page":"e72594","DOI":"10.1371\/journal.pone.0072594","article-title":"Intestinal-specific TNF\u03b1 overexpression induces Crohn\u2019s-like ileitis in mice","volume":"8","author":"Bamias","year":"2013","journal-title":"PLoS One."},{"key":"2025031916354559100_CIT0076","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature14027","article-title":"Growth and host interaction of mouse segmented filamentous bacteria in vitro","volume":"520","author":"Schnupf","year":"2015","journal-title":"Nature."},{"key":"2025031916354559100_CIT0077","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1124\/mol.114.095984","article-title":"Tristetraprolin and its role in regulation of airway inflammation","volume":"87","author":"Prabhala","year":"2015","journal-title":"Mol Pharmacol."},{"key":"2025031916354559100_CIT0078","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/ar1441","article-title":"The tandem CCCH zinc finger protein tristetraprolin and its relevance to cytokine mRNA turnover and arthritis","volume":"6","author":"Carrick","year":"2004","journal-title":"Arthritis Res Ther."},{"key":"2025031916354559100_CIT0079","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.tips.2016.07.002","article-title":"Tristetraprolin as a therapeutic target in inflammatory disease","volume":"37","author":"Patial","year":"2016","journal-title":"Trends Pharmacol Sci."},{"key":"2025031916354559100_CIT0080","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.7150\/thno.30972","article-title":"A novel TNF-\u03b1-targeting aptamer for TNF-\u03b1-mediated acute lung injury and acute liver failure","volume":"9","author":"Lai","year":"2019","journal-title":"Theranostics"},{"key":"2025031916354559100_CIT0081","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1699-0463.1997.tb00567.x","article-title":"TNF blockade in rheumatoid arthritis: implications for therapy and pathogenesis","volume":"105","author":"Maini","year":"1997","journal-title":"APMIS."},{"key":"2025031916354559100_CIT0082","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/S0140-6736(89)90430-3","article-title":"Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis","volume":"2","author":"Brennan","year":"1989","journal-title":"Lancet."},{"key":"2025031916354559100_CIT0083","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00535-017-1401-7","article-title":"Clinical importance of IL-22 cascade in IBD","volume":"53","author":"Mizoguchi","year":"2018","journal-title":"J Gastroenterol."},{"key":"2025031916354559100_CIT0084","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.3390\/ijms222111756","article-title":"Off-target effect of lovastatin disrupts dietary lipid uptake and dissemination through pro-drug inhibition of the mesenteric lymphatic smooth muscle cell contractile apparatus","volume":"22","author":"Stephens","year":"2021","journal-title":"Int J Mol Sci ."},{"key":"2025031916354559100_CIT0085","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaw8412","article-title":"Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials","volume":"11","author":"Lin","year":"2019","journal-title":"Sci Transl Med."}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaf032\/62054705\/jjaf032.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/19\/3\/jjaf032\/62054705\/jjaf032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/19\/3\/jjaf032\/62054705\/jjaf032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T18:41:11Z","timestamp":1742409671000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/doi\/10.1093\/ecco-jcc\/jjaf032\/8030556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,23]]},"references-count":85,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaf032","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,2,23]]},"article-number":"jjaf032"}}