{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T21:54:43Z","timestamp":1777240483308,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The hypothesis is that inflammatory\/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and\/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a \u201cpositive\u201d intestinal inflammation marker and its correlation with lactose tolerance\/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive\/negative results (maldigester\/digester) and the presence\/absence of symptoms reported during LHBT (intolerant\/tolerant), patients were divided into: \u2018lactose tolerants\u2019 (n. 104), \u2018maldigesters\/intolerants\u2019 (n. 187), \u2018digesters\/intolerants\u2019 (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (&gt;15%), extraintestinal symptoms (&gt;30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (&gt;50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters\/intolerants had higher positivity frequencies (p &lt; 0.0001, for both) and absolute values (p = 0.04, for maldigesters\/intolerants) of FCP compared to digesters\/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic\/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients.<\/jats:p>","DOI":"10.3390\/nu15041048","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T03:29:06Z","timestamp":1676863746000},"page":"1048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fecal Calprotectin in Self-Reported Milk Intolerance: Not Only Lactose Intolerance"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4080-2641","authenticated-orcid":false,"given":"Aurelio","family":"Seidita","sequence":"first","affiliation":[{"name":"Unit of Internal Medicine, \u201cV. Cervello\u201d Hospital, Ospedali Riuniti \u201cVilla Sofia-Cervello\u201d, 90120 Palermo, Italy"},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0406-0583","authenticated-orcid":false,"given":"Pasquale","family":"Mansueto","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-5462","authenticated-orcid":false,"given":"Alessandra","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, \u201cV. Cervello\u201d Hospital, Ospedali Riuniti \u201cVilla Sofia-Cervello\u201d, 90120 Palermo, Italy"},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-153X","authenticated-orcid":false,"given":"Marta","family":"Chiavetta","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, \u201cV. Cervello\u201d Hospital, Ospedali Riuniti \u201cVilla Sofia-Cervello\u201d, 90120 Palermo, Italy"},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-555X","authenticated-orcid":false,"given":"Maurizio","family":"Soresi","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-7916","authenticated-orcid":false,"given":"Antonio","family":"Carroccio","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, \u201cV. Cervello\u201d Hospital, Ospedali Riuniti \u201cVilla Sofia-Cervello\u201d, 90120 Palermo, Italy"},{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Internal Medicine Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.nutres.2021.02.003","article-title":"Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment","volume":"89","author":"Catanzaro","year":"2021","journal-title":"Nutr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1136\/pgmj.2004.025551","article-title":"Systemic lactose intolerance: A new perspective on an old problem","volume":"81","author":"Matthews","year":"2005","journal-title":"Postgrad. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1039\/C8FO00555A","article-title":"Lactose malabsorption and intolerance: A review","volume":"9","year":"2018","journal-title":"Food Funct."},{"key":"ref_4","first-page":"36","article-title":"Intolleranza al lattosio nella pratica clinica","volume":"3","year":"2010","journal-title":"Riv. Della Soc. Ital. Med. Gen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF01535754","article-title":"Prediction of lactose malabsorption in referral patients","volume":"33","author":"DiPalma","year":"1988","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/cea.12302","article-title":"BSACI guideline for the diagnosis and management of cow\u2019s milk allergy","volume":"44","author":"Luyt","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1177\/0009922816664512","article-title":"Cow\u2019s Milk Protein Allergy","volume":"55","author":"Mousan","year":"2016","journal-title":"Clin. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Carroccio, A., Soresi, M., Mantia, B., Fayer, F., La Blasca, F., Seidita, A., D\u2019Alcamo, A., Florena, A.M., Tin\u00e8, C., and Garlisi, C. (2021). Whole Cow\u2019s Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow\u2019s Milk Sensitivity in Adults. Nutrients, 13.","DOI":"10.3390\/nu13113833"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.dld.2004.02.009","article-title":"Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice","volume":"36","author":"Rapacciuolo","year":"2004","journal-title":"Dig. Liver Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1373\/49.6.861","article-title":"Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: A prospective study in adults and children","volume":"49","author":"Carroccio","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/2045-7022-4-8","article-title":"Markers of gut mucosal inflammation and cow\u2019s milk specific immunoglobulins in non-IgE cow\u2019s milk allergy","volume":"4","author":"Kolho","year":"2014","journal-title":"Clin. Transl. Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/0016-5085(92)91819-P","article-title":"Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (\u2018celiac sprue\u2019)","volume":"102","author":"Marsh","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/00042737-199910000-00019","article-title":"The histopathology of coeliac disease: Time for a standardized report scheme for pathologists","volume":"11","author":"Oberhuber","year":"1999","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1136\/gutjnl-2019-318404","article-title":"Update on lactose malabsorption and intolerance: Pathogenesis, diagnosis and clinical management","volume":"68","author":"Misselwitz","year":"2019","journal-title":"Gut"},{"key":"ref_15","first-page":"738","article-title":"Country, regional, and global estimates for lactose malabsorption in adults: A systematic review and meta-analysis","volume":"2","author":"Storhaug","year":"2017","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1111\/nmo.12602","article-title":"Self-reported lactose intolerance in clinic patients with functional gastrointestinal symptoms: Prevalence, risk factors, and impact on food choices","volume":"27","author":"Zheng","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/BF01299809","article-title":"Lactose malabsorption and intolerance in Italians. Clinical implications","volume":"31","author":"Bozzani","year":"1986","journal-title":"Dig. Dis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/00365520410005405","article-title":"Lactose malabsorption in a population with irritable bowel syndrome: Prevalence and symptoms. A case-control study","volume":"39","author":"Farup","year":"2004","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_19","first-page":"254","article-title":"Lactose intolerance in adults with chronic unspecific abdominal complaints","volume":"30","author":"Parente","year":"1983","journal-title":"Hepatogastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1111\/j.1440-1746.2007.04986.x","article-title":"Lactose intolerance in patients with irritable bowel syndrome from northern India: A case-control study","volume":"22","author":"Gupta","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/BF01317083","article-title":"Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis","volume":"29","author":"Sciarretta","year":"1984","journal-title":"Dig. Dis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/qjmed\/hcq082","article-title":"Lactose malabsorption and intolerance: A systematic review on the diagnostic value of gastrointestinal symptoms and self-reported milk intolerance","volume":"103","author":"Jellema","year":"2010","journal-title":"QJM"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1097\/MCG.0b013e3181cadbc0","article-title":"Fecal calprotectin concentration in celiac disease","volume":"44","author":"Ertekin","year":"2010","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3109\/00365529209011186","article-title":"Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study","volume":"27","author":"Fagerhol","year":"1992","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/S1590-8658(03)00381-5","article-title":"Role of faecal calprotectin as non-invasive marker of intestinal inflammation","volume":"35","author":"Costa","year":"2003","journal-title":"Dig. Liver Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1097\/MEG.0000000000001731","article-title":"Fecal calprotectin: Current and future perspectives for inflammatory bowel disease treatment","volume":"32","author":"Bertani","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1053\/j.gastro.2016.02.032","article-title":"Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV","volume":"150","author":"Drossman","year":"2016","journal-title":"Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/ecco-jcc\/jjy113","article-title":"European Crohn\u2019s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications","volume":"1","author":"Maaser","year":"2019","journal-title":"J. Crohns Colitis"},{"key":"ref_29","first-page":"425","article-title":"Clinical utility of fecal calprotectin: Potential applications beyond inflammatory bowel disease for the primary care physician","volume":"32","author":"Mari","year":"2019","journal-title":"Ann. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/MEG.0b013e328058ed76","article-title":"Metabolic and inflammatory faecal markers in collagenous colitis","volume":"19","author":"Wildt","year":"2007","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_31","first-page":"97","article-title":"Fecal calprotectin: A marker for clinical differentiation of microscopic colitis and irritable bowel syndrome","volume":"9","author":"Wex","year":"2016","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"287","DOI":"10.18176\/jiaci.0249","article-title":"Testing for Fecal Calprotectin in Food Protein-Induced Enterocolitis Syndrome","volume":"28","author":"Khan","year":"2018","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4168\/aair.2014.6.1.33","article-title":"Can Fecal Calprotectin Level Be Used as a Markers of Inflammation in the Diagnosis and Follow-Up of Cow\u2019s Milk Protein Allergy?","volume":"6","author":"Sancak","year":"2014","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13223-021-00636-0","article-title":"Can fecal calprotectin levels be used to monitor infant milk protein allergies?","volume":"17","author":"Qiu","year":"2021","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"945212","DOI":"10.3389\/fped.2022.945212","article-title":"Fecal calprotectin levels in pediatric cow\u2019s milk protein allergy","volume":"9","author":"Emmert","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1159\/000525961","article-title":"Fecal Calprotectin in Children with Cow\u2019s Milk Protein Allergy: A Systematic Review and Meta-Analysis","volume":"183","author":"Zhang","year":"2022","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1136\/bmj.287.6405.1593","article-title":"Allergy to cows\u2019 milk presenting as chronic constipation","volume":"287","author":"Chin","year":"1983","journal-title":"Br. Med. J. (Clin. Res. Ed.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1056\/NEJM199810153391602","article-title":"Intolerance of cow\u2019s milk and chronic constipation in children","volume":"339","author":"Iacono","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0022-3476(95)70496-5","article-title":"Chronic constipation as a symptom of cow milk allergy","volume":"126","author":"Iacono","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1056\/NEJM199903183401114","article-title":"Cow\u2019s milk and chronic constipation in children","volume":"340","author":"Shah","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/j.1365-2036.2006.03125.x","article-title":"Review article: Chronic constipation and food hypersensitivity--an intriguing relationship","volume":"24","author":"Carroccio","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1080\/00365520500367400","article-title":"Multiple food hypersensitivity as a cause of refractory chronic constipation in adults","volume":"41","author":"Carroccio","year":"2006","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.dld.2022.06.023","article-title":"Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis","volume":"54","author":"Zingone","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1038\/ajg.2013.353","article-title":"Non-celiac wheat sensitivity as an allergic condition: Personal experience and narrative review","volume":"108","author":"Carroccio","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1053\/j.gastro.2019.03.046","article-title":"Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E","volume":"157","author":"Pflaum","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cgh.2009.11.010","article-title":"A cytologic assay for diagnosis of food hypersensitivity in patients with irritable bowel syndrome","volume":"8","author":"Carroccio","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/ajg.2012.236","article-title":"Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity","volume":"107","author":"Carroccio","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.gastro.2014.07.046","article-title":"Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome","volume":"147","author":"Schuppan","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lapides, R.A., and Savaiano, D.A. (2018). Gender, Age, Race and Lactose Intolerance: Is There Evidence to Support a Differential Symptom Response? A Scoping Review. Nutrients, 11.","DOI":"10.3390\/nu10121956"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1007\/s10620-020-06743-z","article-title":"Differential Cytokine Expression in the Duodenum and Rectum of Children with Non-Immunoglobulin E-Mediated Cow\u2019s Milk Protein Allergy","volume":"66","year":"2021","journal-title":"Dig. Dis. Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/4\/1048\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:00Z","timestamp":1760121420000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/4\/1048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,20]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["nu15041048"],"URL":"https:\/\/doi.org\/10.3390\/nu15041048","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,20]]}}}