{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:34:01Z","timestamp":1764678841318,"version":"3.46.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gut Pathog"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fecal calprotectin is widely used as a non-invasive biomarker for intestinal inflammation, particularly in inflammatory bowel disease (IBD), the most common clinical context for its use, where misinterpretation can lead to unnecessary invasive procedures or inappropriate therapy escalation. However, its specificity has been questioned due to elevated levels observed in non-intestinal conditions. Here, we investigated whether nasopharyngeal viral infections contribute to elevated fecal calprotectin, thereby confounding its diagnostic interpretation. Bioinformatic analysis revealed high constitutive expression of calprotectin subunits (S100A8\/A9) in squamous epithelia of the upper aerodigestive tract compared with distal gut mucosa. To assess gastrointestinal stability of epithelial-derived calprotectin, healthy volunteers ingested porcine calprotectin, which was subsequently detected in feces, demonstrating resistance to intestinal degradation. In a retrospective cohort, patients with non-SARS-CoV-2 respiratory viral infections displayed significantly higher fecal calprotectin levels than SARS-CoV-2 patients (447\u00a0\u00b5g\/g vs. 82\u00a0\u00b5g\/g,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), despite limited gastrointestinal involvement. Nasopharyngeal calprotectin levels did not differ significantly between viral etiologies, but in COVID-19 patients, fecal calprotectin positively correlated with nasopharyngeal calprotectin (\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.43,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008) and viral load (\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.13,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.026). These findings suggest that calprotectin released from proximal epithelial tissues during viral infection can persist through the gastrointestinal tract and influence fecal calprotectin levels, underscoring the importance of contextual interpretation of this biomarker and the value of incorporating virological assessment into diagnostic workflows.\n                  <\/jats:p>","DOI":"10.1186\/s13099-025-00780-7","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:30:48Z","timestamp":1764678648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nasopharyngeal viral infection as a source of elevated fecal calprotectin: a diagnostic pitfall in intestinal inflammation"],"prefix":"10.1186","volume":"17","author":[{"given":"Chun-Ting","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-5536","authenticated-orcid":false,"given":"Annemiek A.","family":"van der Eijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-7395","authenticated-orcid":false,"given":"Jolanda J.C.","family":"Voermans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanneke J.","family":"van Vuuren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-6028","authenticated-orcid":false,"given":"Maikel P.","family":"Peppelenbosch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-1816","authenticated-orcid":false,"given":"Vincent T.","family":"Janmaat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"780_CR1","doi-asserted-by":"crossref","unstructured":"Aharoni-Frutkoff Y et al. Whole Food Diet Induces Remission in Children and Young Adults With Mild to Moderate Crohn\u2019s Disease and Is More Tolerable Than Exclusive Enteral Nutrition: A Randomized Controlled Trial. Gastroenterology, 2025.","DOI":"10.1053\/j.gastro.2025.06.011"},{"issue":"5","key":"780_CR2","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1053\/j.gastro.2024.12.024","volume":"168","author":"RP Hirten","year":"2025","unstructured":"Hirten RP, et al. Physiological data collected from wearable devices identify and predict inflammatory bowel disease flares. Gastroenterology. 2025;168(5):939\u2013e9515.","journal-title":"Gastroenterology"},{"issue":"1","key":"780_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1053\/j.gastro.2020.03.065","volume":"159","author":"KS Cheung","year":"2020","unstructured":"Cheung KS, et al. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong cohort: systematic review and Meta-analysis. Gastroenterology. 2020;159(1):81\u201395.","journal-title":"Gastroenterology"},{"issue":"4","key":"780_CR4","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/jpn3.12464","volume":"80","author":"P Villalba-Davila","year":"2025","unstructured":"Villalba-Davila P, et al. Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers. J Pediatr Gastroenterol Nutr. 2025;80(4):617\u201322.","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"6","key":"780_CR5","doi-asserted-by":"publisher","first-page":"986","DOI":"10.24953\/turkjped.2020.06.010","volume":"62","author":"OY Aksoy","year":"2020","unstructured":"Aksoy OY, et al. Fecal calprotectin levels in Helicobacter pylori gastritis in children. Turk J Pediatr. 2020;62(6):986\u201393.","journal-title":"Turk J Pediatr"},{"key":"780_CR6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4103\/ijpvm.IJPVM_507_20","volume":"13","author":"M Rafeey","year":"2022","unstructured":"Rafeey M, Nikmanesh P, Javadzadeh F. Diagnostic value of fecal calprotectin in children with Gastritis, duodenitis and Helicobacter pylori. Int J Prev Med. 2022;13:107.","journal-title":"Int J Prev Med"},{"key":"780_CR7","doi-asserted-by":"crossref","unstructured":"Sejersen K, Eriksson MB, Larsson AO. Calprotectin as a biomarker for infectious diseases: A comparative review with conventional inflammatory markers. Int J Mol Sci, 2025. 26(13):6476.","DOI":"10.3390\/ijms26136476"},{"issue":"4","key":"780_CR8","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1053\/j.gastro.2025.03.016","volume":"169","author":"RE Prentice","year":"2025","unstructured":"Prentice RE, et al. Active inflammatory bowel disease on intestinal ultrasound during pregnancy is associated with an increased risk of adverse pregnancy and neonatal outcomes independent of clinical and biochemical disease activity. Gastroenterology. 2025;169(4):647\u201362.","journal-title":"Gastroenterology"},{"issue":"1","key":"780_CR9","doi-asserted-by":"publisher","first-page":"3354","DOI":"10.1038\/s41467-021-23641-8","volume":"12","author":"VT Janmaat","year":"2021","unstructured":"Janmaat VT, et al. HOXA13 in etiology and oncogenic potential of barrett\u2019s esophagus. Nat Commun. 2021;12(1):3354.","journal-title":"Nat Commun"},{"issue":"7","key":"780_CR10","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1093\/ecco-jcc\/jjad034","volume":"17","author":"T Winogrodzki","year":"2023","unstructured":"Winogrodzki T, et al. TNF deltaare pigs: A translational crohn\u2019s disease model. J Crohns Colitis. 2023;17(7):1128\u201338.","journal-title":"J Crohns Colitis"},{"issue":"5","key":"780_CR11","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1370\/afm.1949","volume":"14","author":"GA Holtman","year":"2016","unstructured":"Holtman GA, et al. Diagnostic accuracy of fecal calprotectin for pediatric inflammatory bowel disease in primary care: A prospective cohort study. Ann Fam Med. 2016;14(5):437\u201345.","journal-title":"Ann Fam Med"},{"issue":"1","key":"780_CR12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1053\/j.gastro.2024.08.031","volume":"168","author":"PA Olivera","year":"2025","unstructured":"Olivera PA, et al. Healthy First-Degree relatives from multiplex families vs simplex families have higher subclinical intestinal Inflammation, a distinct fecal microbial Signature, and harbor a higher risk of developing crohn\u2019s disease. Gastroenterology. 2025;168(1):99\u2013110. e2.","journal-title":"Gastroenterology"},{"issue":"7","key":"780_CR13","first-page":"699","volume":"69","author":"J Murray","year":"2023","unstructured":"Murray J, Kok KB, Ayling RM. Fecal Calprotectin Gastrointest Disease Clin Chem. 2023;69(7):699\u2013710.","journal-title":"Fecal Calprotectin Gastrointest Disease Clin Chem"},{"issue":"8","key":"780_CR14","doi-asserted-by":"publisher","first-page":"e15158","DOI":"10.1111\/exd.15158","volume":"33","author":"W Abdi","year":"2024","unstructured":"Abdi W, et al. An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies. Exp Dermatol. 2024;33(8):e15158.","journal-title":"Exp Dermatol"}],"container-title":["Gut Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13099-025-00780-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13099-025-00780-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13099-025-00780-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:30:50Z","timestamp":1764678650000},"score":1,"resource":{"primary":{"URL":"https:\/\/gutpathogens.biomedcentral.com\/articles\/10.1186\/s13099-025-00780-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["780"],"URL":"https:\/\/doi.org\/10.1186\/s13099-025-00780-7","relation":{},"ISSN":["1757-4749"],"issn-type":[{"value":"1757-4749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"25 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was reviewed by the Medical Ethics Review Committee (METC) of Erasmus MC, Rotterdam, The Netherlands. The Committee concluded that the study does not fall under the scope of the Dutch Medical Research Involving Human Subjects Act (WMO) (reference number: MEC-2021-0626) and is therefore not subject to formal ethics approval. Written informed consent was not required in accordance with this decision.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"95"}}