{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:04:14Z","timestamp":1784754254822,"version":"3.55.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"7","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01A115845"],"award-info":[{"award-number":["R01A115845"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Affairs MERIT Review","award":["I01BX004630"],"award-info":[{"award-number":["I01BX004630"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea in the United States. Gut dysbiosis and chronic inflammation are key contributors to CDI susceptibility and severity. Metabolic syndrome (MetS)\u2014defined by central obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and type 2 diabetes mellitus (T2DM)\u2014is increasingly prevalent worldwide and is characterized by chronic immune dysregulation and alterations in gut microbiota. These pathophysiologic features may overlap with mechanisms that predispose individuals to CDI and its complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Using a large electronic health record database encompassing 102 health care organizations, we examined the association between metabolic conditions (MetS, obesity, and T2DM) and the risk of CDI diagnosis and severe clinical outcomes. Individuals with a diagnosis of each metabolic condition were compared with matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 3 metabolic conditions were associated with an increased risk of CDI. The strongest association was observed in patients with MetS (odds ratio [OR], 1.94), followed by obesity (OR, 1.14) and T2DM (OR, 1.11). The impact of metabolic disorders on CDI severity varied based on the specific condition. Patients with MetS and obesity were more likely to develop sepsis, leukocytosis, and neutrophilia and to require ICU admission; however, they had lower risk of hypoalbuminemia, recurrent CDI, and all-cause mortality. In contrast, patients with T2DM had greater odds of developing all of the CDI-associated complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MetS, obesity, and T2DM were all associated with an increased likelihood of CDI diagnosis. However, their effects on CDI severity varied among the 3 conditions examined\u2014patients with T2DM had the greatest risk of adverse outcomes, including sepsis, ICU admission, recurrent CDI, and mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag419","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:39:11Z","timestamp":1784374751000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Syndrome Is Associated With Increased Risk of\n                    <i>Clostridioides difficile<\/i>\n                    Infection Diagnosis and Severe Outcomes"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6758-4113","authenticated-orcid":false,"given":"Stella O","family":"Oyewole","sequence":"first","affiliation":[{"name":"Pathobiology and Molecular Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio ,","place":["USA"]},{"name":"Infectious Disease Division, Department of Internal Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9821-1257","authenticated-orcid":false,"given":"Rajat","family":"Madan","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Department of Internal Medicine, University of Arizona , Tucson, Arizona ,","place":["USA"]},{"name":"Veterans Affairs Medical Center , Tucson, Arizona ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"2026072216160905800_ofag419-B1","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa1408913","article-title":"Burden of Clostridium difficile infection in the United States","volume":"372","author":"Lessa","year":"2015","journal-title":"N Engl J Med"},{"key":"2026072216160905800_ofag419-B2","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1056\/NEJMoa1910215","article-title":"Trends in U.S. burden of Clostridioides difficile infection and outcomes","volume":"382","author":"Guh","year":"2020","journal-title":"N Engl J Med"},{"key":"2026072216160905800_ofag419-B3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12879-023-08096-0","article-title":"The burden of CDI in the United States: a multifactorial challenge","volume":"23","author":"Feuerstadt","year":"2023","journal-title":"BMC Infect Dis"},{"key":"2026072216160905800_ofag419-B4","volume-title":"Clostridioides difficile Infection.","author":"Mada","year":"2025"},{"key":"2026072216160905800_ofag419-B5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/s-0040-1701229","article-title":"Clostridium difficile infection: an epidemiology update","volume":"33","author":"De Roo","year":"2020","journal-title":"Clin Colon Rectal Surg"},{"key":"2026072216160905800_ofag419-B6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/apt.13832","article-title":"Body mass index greater than 35 is associated with severe Clostridium difficile infection","volume":"45","author":"Mulki","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"2026072216160905800_ofag419-B7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.molimm.2014.09.005","article-title":"The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection","volume":"63","author":"Sun","year":"2015","journal-title":"Mol Immunol"},{"key":"2026072216160905800_ofag419-B8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3390\/antibiotics14020133","article-title":"Risk factors for Clostridium difficile infection in inpatients: a four-year (2017\u20132020) retrospective study","volume":"14","author":"Hsia","year":"2025","journal-title":"Antibiotics (Basel)"},{"key":"2026072216160905800_ofag419-B9","doi-asserted-by":"crossref","first-page":"e00180-20","DOI":"10.1128\/mBio.00180-20","article-title":"Systemic inflammatory mediators are effective biomarkers for predicting adverse outcomes in Clostridioides difficile infection","volume":"11","author":"Dieterle","year":"2020","journal-title":"mBio"},{"key":"2026072216160905800_ofag419-B10","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3390\/microorganisms7100435","article-title":"Characterization of the immune response during infection caused by Clostridioides difficile","volume":"7","author":"Hamo","year":"2019","journal-title":"Microorganisms"},{"key":"2026072216160905800_ofag419-B11","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1464-5491.2006.01858.x","article-title":"Metabolic syndrome\u2014a new world-wide definition. 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