{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:46:28Z","timestamp":1790833588048,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Allergy Therapeutics Italia","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Milk is a fundamental component of the diet of every mammal; nevertheless, not every individual can tolerate this kind of food, especially in adulthood. However, lactose intolerance has only been recognized in the last 50 years, and currently, lactose intolerance is defined as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhoea that occur after lactose consumption. Lactose is currently a common disaccharide in human nutrition, both in breastfed infants and in adults, but its digestion requires a specialized enzyme called lactase. The genetically programmed reduction in lactase activity during adulthood affects most of the world\u2019s adult population and can cause troublesome digestive symptoms, which may also vary depending on the amount of residual lactase activity; the small bowel transit time; and, especially, the amount of ingested lactose. Several diagnostic tests are currently available for lactose intolerance, but the diagnosis remains challenging. The treatment for lactose intolerance mainly consists of reducing or eliminating the dietetic amount of lactose until the symptoms disappear, but this is hard to achieve, as lactose is present in dairy products and is even commonly used as a food additive. In addition to dietetic restriction of lactose-containing foods, lactase can be administered as an enzymatic food supplement, but its efficacy is still controversial. Recently, probiotics have been proposed for the management of lactose intolerance; certain probiotic strains have shown specific \u03b2-galactosidase activity, thus aiding in the digestion of lactose. The aim of this paper was to review the current knowledge about lactose intolerance and to discuss the potential for the use of specific probiotic strains such as dietary supplements in lactose-intolerant patients.<\/jats:p>","DOI":"10.3390\/nu10111599","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T11:31:47Z","timestamp":1541071907000},"page":"1599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review with a Focus on Current Management and Future Perspectives"],"prefix":"10.3390","volume":"10","author":[{"given":"Filippo","family":"Fassio","sequence":"first","affiliation":[{"name":"Allergy and Clinical Immunology Unit, Azienda Usl Toscana Centro, Ospedale San Giovanni di Dio, 50143 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sole","family":"Facioni","sequence":"additional","affiliation":[{"name":"AILI\u2014Associazione Italiana Latto-Intolleranti Onlus, 55100 Lucca, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Guagnini","sequence":"additional","affiliation":[{"name":"Allergy Therapeutics Italia, via IV Novembre 76, 20190 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"ref_1","first-page":"36","article-title":"Intolleranza al lattosio nella pratica clinica","volume":"3","year":"2010","journal-title":"Rivista della Societ\u00e0 Italiana di Medicina Generale"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1111\/j.1742-1241.2008.01834.x","article-title":"A re-appraisal of lactose intolerance","volume":"62","author":"Harrington","year":"2008","journal-title":"Int. J. Clin. Pract."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1111\/1462-2920.12117","article-title":"Nutrition, population growth and disease: A short history of lactose","volume":"15","year":"2013","journal-title":"Environ. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1365-2036.2007.03557.x","article-title":"Review article: Lactose intolerance in clinical practice\u2014And realities","volume":"27","author":"Lomer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8020","DOI":"10.3390\/nu7095380","article-title":"Lactose intolerance in adults: Biological mechanism and dietary management","volume":"7","author":"Deng","year":"2015","journal-title":"Nutrients"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3184\/003685009X12547510332240","article-title":"The molecular basis of lactose intolerance","volume":"92","author":"Campbell","year":"2009","journal-title":"Sci. Prog."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1017\/S1751731111001935","article-title":"The evolution of milk secretion and its ancient origins","volume":"6","author":"Oftedal","year":"2012","journal-title":"Animal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng826","article-title":"Identification of a variant associated with adult-type hypolactasia","volume":"30","author":"Enattah","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Itan, Y., Jones, B.L., Ingram, C.J., Swallow, D.M., and Thomas, M.G. (2010). A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol. Biol., 10.","DOI":"10.1186\/1471-2148-10-36"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.clinbiochem.2008.01.006","article-title":"Single nucleotide polymorphism c\/t-13910, located upstream of the lactase gene, associated with adult-type hypolactasia: Validation for clinical practice","volume":"41","author":"Mattar","year":"2008","journal-title":"Clin. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bbagen.2005.02.003","article-title":"Adult-type hypolactasia and regulation of lactase expression","volume":"1723","author":"Troelsen","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/ng1946","article-title":"Convergent adaptation of human lactase persistence in Africa and Europe","volume":"39","author":"Tishkoff","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/2050640613484463","article-title":"Lactose malabsorption and intolerance: Pathogenesis, diagnosis and treatment","volume":"1","author":"Misselwitz","year":"2013","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1542\/peds.2006-1721","article-title":"Committee on Nutrition. Lactose intolerance in infants, children, and adolescents","volume":"118","author":"Heyman","year":"2006","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev.nu.09.070189.002355","article-title":"Current concepts in lactose malabsorption and intolerance","volume":"9","author":"Saavedra","year":"1989","journal-title":"Annu. Rev. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.genet.37.110801.143820","article-title":"Genetics of lactase persistence and lactose intolerance","volume":"37","author":"Swallow","year":"2003","journal-title":"Annu. Rev. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (EFSA) (2010). Scientific opinion on lactose thresholds in lactose intolerance and galactosaemia. EFSA J., 8, 1777.","DOI":"10.2903\/j.efsa.2010.1777"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/MEG.0000000000000089","article-title":"Perception of lactose intolerance in irritable bowel syndrome patients","volume":"26","author":"Dainese","year":"2014","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"797","DOI":"10.7326\/0003-4819-152-12-201006150-00241","article-title":"Systematic review: Effective management strategies for lactose intolerance","volume":"152","author":"Shaukat","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/MCG.0b013e31824e9132","article-title":"A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance","volume":"47","author":"Furnari","year":"2013","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/ajg.2010.146","article-title":"Lactose intolerance and the role of the lactose breath test","volume":"105","author":"Law","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/ajg.2017.46","article-title":"Hydrogen and methane-based breath testing in gastrointestinal disorders: The North American consensus","volume":"112","author":"Rezaie","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/apt.12306","article-title":"Fructose and lactose intolerance and malabsorption testing: The relationship with symptoms in functional gastrointestinal disorders","volume":"37","author":"Materna","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_25","first-page":"900","article-title":"Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment","volume":"104","author":"Pohl","year":"2010","journal-title":"Columbia J. Nutr."},{"key":"ref_26","unstructured":"(2018, May 01). The European Parliament and the Council of the European Union: Regulation (EU) No 1169\/2011 of the European Parliament and of the Council of 25 October 2011 on the provision of food information to Consumers, Amending Regulations (EC) No 1924\/2006 and (EC) No 1925\/2006 of the European Parliament and of the Council. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2011\/1169\/oj."},{"key":"ref_27","first-page":"163","article-title":"The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: Randomized trial","volume":"14","author":"Ojetti","year":"2010","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/sj.ejcn.1602098","article-title":"Effect of exogenous \u03b2-galactosidase in patients with lactose malabsorption and intolerance: A crossover double-blind placebo-controlled study","volume":"59","author":"Montalto","year":"2005","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/ajcn\/64.2.232","article-title":"Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance","volume":"64","author":"Hertzler","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1136\/gut.41.5.632","article-title":"Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: A placebo effect?","volume":"41","author":"Briet","year":"1997","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.dld.2004.12.007","article-title":"Rifaximin in patients with lactose intolerance","volume":"37","author":"Cappello","year":"2005","journal-title":"Dig. Liver Dis."},{"key":"ref_32","unstructured":"Joint FAO\/WHO Expert Consultation (2001). Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria, FAO\/WHO."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0002-8223(21)11695-5","article-title":"Lactose intolerance and fermented dairy products","volume":"65","author":"Gallagher","year":"1974","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1251S","DOI":"10.3945\/ajcn.113.073023","article-title":"Lactose digestion from yogurt: Mechanism and relevance","volume":"99","author":"Savaiano","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/0884533612440289","article-title":"Beneficial effects of long-term consumption of a probiotic combination of lactobacillus casei shirota and bifidobacterium breve yakult may persist after suspension of therapy in lactose-intolerant patients","volume":"27","author":"Almeida","year":"2012","journal-title":"Nutr. Clical Pr."},{"key":"ref_36","first-page":"595","article-title":"Effects of yogurt and bifidobacteria supplementation on the colonic microbiota in lactose-intolerant subjects","volume":"104","author":"He","year":"2007","journal-title":"J. Appl. Microbiol."},{"key":"ref_37","unstructured":"FAO\/WHO (2002). Guidelines for the Evaluation of Probiotics in Food, FAO\/WHO. Joint FAO\/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document: The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.3748\/wjg.v18.i30.4012","article-title":"Clinical trial: Lactobacillus plantarum 299v (dsm 9843) improves symptoms of irritable bowel syndrome","volume":"18","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1007\/s10620-007-0196-4","article-title":"Therapeutic effect of lactobacillus acidophilus-sdc 2012, 2013 in patients with irritable bowel syndrome","volume":"53","author":"Sinn","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rossi, R., Rossi, L., and Fassio, F. (2015). Clinical follow-up of 96 patients affected by irritable bowel syndrome treated with a novel multi-strain symbiotic. J. Contemp. Immunol.","DOI":"10.7726\/jci.2015.1003"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00253-012-3977-4","article-title":"Lactococcus lactis expressing food-grade \u03b2-galactosidase alleviates lactose intolerance symptoms in post-weaning Balb\/c mice","volume":"96","author":"Li","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/ajcn\/69.1.140","article-title":"A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance","volume":"69","author":"Saltzman","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/1040841X.2010.536522","article-title":"Beneficial effects of lactic acid bacteria on human beings","volume":"37","author":"Masood","year":"2011","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/gutjnl-2012-302504","article-title":"An update on the use and investigation of probiotics in health and disease","volume":"62","author":"Sanders","year":"2013","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3920\/BM2015.0051","article-title":"In vitro evidence for efficacy in food intolerance for the multispecies probiotic formulation ecologic\u00ae tolerance (syngutTM)","volume":"7","author":"Heath","year":"2016","journal-title":"Benef. Microbes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0019-2791(72)90087-0","article-title":"Glycopeptides of human immunoglobulins. 3. The use and preparation of specific glycosidases","volume":"9","author":"Miller","year":"1972","journal-title":"Immunochemistry"},{"key":"ref_48","first-page":"1","article-title":"The effects of probiotics in lactose intolerance: A systematic review","volume":"8398","author":"Oak","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/11\/1599\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:27:16Z","timestamp":1760196436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/11\/1599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["nu10111599"],"URL":"https:\/\/doi.org\/10.3390\/nu10111599","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,1]]}}}