{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:39Z","timestamp":1785409839736,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014786","name":"Northern Border University","doi-asserted-by":"publisher","award":["NBU-FFR-2026-52-00"],"award-info":[{"award-number":["NBU-FFR-2026-52-00"]}],"id":[{"id":"10.13039\/501100014786","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NBU-FFR-2026-52-00"],"award-info":[{"award-number":["NBU-FFR-2026-52-00"]}],"id":[{"id":"https:\/\/ror.org\/03j9tzj20","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019217","name":"Almaarefa University","doi-asserted-by":"crossref","award":["MHIRSP-005"],"award-info":[{"award-number":["MHIRSP-005"]}],"id":[{"id":"10.13039\/100019217","id-type":"DOI","asserted-by":"crossref"}]},{"award":["MHIRSP-005"],"award-info":[{"award-number":["MHIRSP-005"]}],"id":[{"id":"https:\/\/ror.org\/00s3s5518","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Differentiating inflammatory bowel disease (IBD) from diarrhea-predominant irritable bowel syndrome (IBS-D) remains a major clinical challenge due to overlapping symptoms and the limited specificity of single biomarkers. A reliable, non-invasive multimarker approach is needed to improve diagnostic accuracy and reduce unnecessary endoscopic procedures. To evaluate the diagnostic performance of serum interleukin-17A (IL-17A), neutrophil-to-albumin ratio (NAR), and fecal calprotectin (FCP), individually and in combination, for discriminating IBD from IBS-D and healthy controls in Egyptian patients. In this case\u2013control study, 300 participants (100 with IBD, 100 with IBS-D, and 100 healthy controls) were enrolled. Serum IL-17A, NAR, and FCP were measured, and subgroup analysis was performed for infected and non-infected IBS-D patients. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cutoffs determined by the Youden index. A combined biomarker model was constructed using logistic regression. All biomarkers demonstrated a significant stepwise increase from healthy controls to IBS-D and IBD (p &lt; 0.001). IL-17A, NAR, and FCP were elevated in IBS-D compared with controls, indicating low-grade inflammation, but were highest in IBD. No significant differences were observed between infected and non-infected IBS-D patients. Among individual markers, NAR showed the highest diagnostic accuracy (AUC = 0.923), followed by FCP (AUC = 0.884) and IL-17A (AUC = 0.859). The combined model significantly improved performance (AUC = 0.973), achieving 89% sensitivity and 96% specificity. IBS-D is associated with measurable systemic and intestinal inflammation independent of infection status. The combined biomarker model integrating IL-17A, neutrophil\u2013albumin ratio, and fecal calprotectin demonstrated promising discriminatory performance for differentiating IBD from IBS-D. These findings suggest the potential applicability of combined non-invasive biomarkers in future diagnostic stratification approaches. However, the model was developed and evaluated within a single cohort, and external validation in independent populations is required before future potential clinical application. A multimarker diagnostic panel integrating IL-17A, neutrophil\u2013albumin ratio, and fecal calprotectin demonstrated promising diagnostic performance for differentiating inflammatory bowel disease from IBS-D. The combined model may contribute to future diagnostic stratification strategies in patients with chronic diarrhea. However, these findings were derived from a single cohort and require validation in independent populations before broader clinical application.<\/jats:p>","DOI":"10.3390\/ijms27125450","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:27:21Z","timestamp":1781666841000},"page":"5450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Invasive Multimarker Strategy Combining IL-17A, Neutrophil\u2013Albumin Ratio, and Fecal Calprotectin for Accurate Discrimination of IBD from IBS-D"],"prefix":"10.3390","volume":"27","author":[{"given":"Gamal","family":"Othman","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 24341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-0248","authenticated-orcid":false,"given":"Maysaa","family":"El Sayed Zaki","sequence":"additional","affiliation":[{"name":"Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 24341, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Elmalki Elmalki","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura 24341, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelnaser A.","family":"Badawy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar City 35516, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir A.","family":"Afifi","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig 41233, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1053\/j.gastro.2022.12.007","article-title":"AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis","volume":"164","author":"Singh","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/00365521.2016.1235224","article-title":"Neutrophils in ulcerative colitis: A review of selected biomarkers and their potential therapeutic implications","volume":"52","author":"Muthas","year":"2017","journal-title":"Scand. 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