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Several markers have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, none is sufficiently reliable to enable accurate diagnosis. We characterized a broad panel of serum proteins to assess disease-specific biomarker profiles and associate these findings with faecal microbiota composition in newly diagnosed IBD and IBS patients and healthy individuals. The study cohort consisted of 49 newly diagnosed treatment-na\u00efve adult patients (13 Crohn\u2019s disease (CD), 13 ulcerative colitis (UC), and 23 IBS) and 12 healthy individuals. Inflammatory and metabolism-related serum proteins were assessed using PEA multiplex panels, while gut microbiota composition was determined by 16\u00a0s rRNA gene amplicon sequencing. Serum proteins AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK were identified as markers with the most promising specificity\/sensitivity and predictivity between healthy and disease groups, while IL-17A and TNFRSF9 enabled differentiation between IBD and IBS patients. Increased abundance of <jats:italic>Enterobacteriaceae<\/jats:italic> was associated with protein markers significantly elevated in IBD\/IBS. In contrast, depletion of beneficial taxa like <jats:italic>Ruminococcaceae<\/jats:italic> and <jats:italic>Verucomicrobiaceae<\/jats:italic> (i.e. <jats:italic>Akkermansia muciniphila<\/jats:italic>) was associated with decrease of a set of markers in diseased groups. Differences in the abundance of <jats:italic>Turicibacteriaceae<\/jats:italic> were more predictive to discern CD from UC than any of the serum proteins investigated. By using a broad panel of inflammation and metabolism-related proteins, we determined serum markers with significantly different levels in treatment-na\u00efve IBD and IBS patients compared to healthy individuals, as well as between IBD and IBS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:bold>Key messages<\/jats:bold>\n            <\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Significant changes in the levels of several serum proteins and abundances of faecal bacterial taxa between study groups were found.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Increased levels of AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK characterize both IBD and IBS, while IL-17A and TNFRSF9 differentiate IBD from IBS.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Increase of <jats:italic>Enterobacteriaceae<\/jats:italic> and depletion of beneficial taxa <jats:italic>Ruminococcaceae<\/jats:italic> and <jats:italic>Verucomicrobiaceae<\/jats:italic> (i.e. <jats:italic>Akkermansia muciniphila<\/jats:italic>) was found in IBD and IBS. Differences in <jats:italic>Turicibacteriaceae<\/jats:italic> were more predictive to discern CD from UC than any of the serum proteins investigated.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00109-025-02558-5","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T03:59:33Z","timestamp":1749268773000},"page":"963-974","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Serum proteins and faecal microbiota as potential biomarkers in newly diagnosed, treatment-na\u00efve inflammatory bowel disease and irritable bowel syndrome patients"],"prefix":"10.1007","volume":"103","author":[{"given":"Mario","family":"Matija\u0161i\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1303-3031","authenticated-orcid":false,"given":"Anja","family":"Bare\u0161i\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-3156","authenticated-orcid":false,"given":"Hana","family":"\u010cip\u010di\u0107 Paljetak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Peri\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Panek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Kunovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ljubas Kele\u010di\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darija","family":"Vrane\u0161i\u0107 Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Grubeli\u0107 Ravi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Rogi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Antolic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Horvat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Kraljevi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Bani\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Krznari\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Verbanac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"2558_CR1","doi-asserted-by":"publisher","unstructured":"Matija\u0161i\u0107 M, Me\u0161trovi\u0107 T, Peri\u0107 M, \u010cip\u010di\u0107Paljetak H, Panek M, Vrane\u0161i\u0107 Bender D, LjubasKele\u010di\u0107 D, Krznari\u0107 \u017d, Verbanac D (2016) Modulating composition and metabolic activity of the gut microbiota in IBD patients. 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