{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:04:45Z","timestamp":1782972285818,"version":"3.54.5"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"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>Background\/Objectives: Functional constipation (FC) commonly affects middle-aged and older adults, but current pharmacological treatments have limitations. Postbiotics may offer safety advantages, but clinical evidence is limited. This randomized controlled trial evaluated the efficacy and safety of a heat-inactivated two-strain Lacticaseibacillus paracasei fermented milk in adults with FC. Methods: One hundred adults aged 45\u201375 years with Rome IV-defined FC received the fermented milk or placebo for 4 weeks. The primary outcome was the change in weekly spontaneous bowel movement (SBM) frequency from baseline to week 4. Secondary outcomes included complete spontaneous bowel movement (CSBM) frequency, whole-gut transit time (WGTT), constipation symptom scores, quality of life, serum biomarkers, and adverse events. Primary analysis was per-protocol (n = 96); intention-to-treat analysis was applied to primary and key secondary outcomes. Results: Dropout was 4% (n = 4, 2 per group), and adherence was &gt;80% in both groups. The intervention showed no significant benefit over placebo for the primary outcome or for most secondary clinical outcomes. Although both groups improved within-group, no significant between-group differences were observed at week 4 for changes in SBM (MD = \u22120.14, 95% CI: \u22120.85, 0.57; p = 0.683), CSBM (MD = 0.27, 95% CI: \u22120.61, 1.15; p = 0.543), or WGTT (MD = \u22121.55 h, 95% CI: \u22127.65, 4.55; p = 0.614). Symptom and quality-of-life scores also did not differ between groups. Exploratory biomarker analyses showed significantly greater increases in serum VIP and ACh in the intervention group (VIP: MD = 105.23 ng\/L, p &lt; 0.001; ACh: MD = 42.95 ng\/L, p = 0.035). No adverse events were reported. Conclusions: Four weeks of this postbiotic was safe but did not significantly improve bowel function or symptoms in the overall FC population. The increases in serum VIP and ACh suggest engagement of neurotransmitter-related pathways; however, these exploratory findings do not imply causation or clinical efficacy and warrant confirmation in longer-duration trials (Clinical Trial Registry: ChiCTR2500111771).<\/jats:p>","DOI":"10.3390\/nu18132114","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Heat-Inactivated Two-Strain Lacticaseibacillus paracasei Fermented Milk as a Postbiotic for Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6893-8456","authenticated-orcid":false,"given":"Xinyi","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanglian","family":"Lan","sequence":"additional","affiliation":[{"name":"National Technology Innovation Center for Dairy, Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langrun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0094-711X","authenticated-orcid":false,"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Technology Innovation Center for Dairy, Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"He","sequence":"additional","affiliation":[{"name":"National Technology Innovation Center for Dairy, Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixu","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Probiotics, China Agricultural University, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2427-9064","authenticated-orcid":false,"given":"Jingjing","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1053\/j.gastro.2016.03.035","article-title":"Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction","volume":"150","author":"Drossman","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S2468-1253(21)00111-4","article-title":"Global prevalence of functional constipation according to the Rome criteria: A systematic review and meta-analysis","volume":"6","author":"Barberio","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Du, X., Liu, S., Jia, P., Wang, X., Gan, J., Hu, W., Zhu, H., Song, Y., Niu, J., and Ji, Y. (2022). Epidemiology of Constipation in Elderly People in Parts of China: A Multicenter Study. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.823987"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nrgastro.2016.53","article-title":"Diagnosis and management of chronic constipation in adults","volume":"13","author":"Rao","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/j.1365-2036.2011.04809.x","article-title":"Epidemiology of functional constipation and comparison with constipation-predominant irritable bowel syndrome: The Systematic Investigation of Gastrointestinal Diseases in China (SILC)","volume":"34","author":"Zhao","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1053\/j.gastro.2019.12.034","article-title":"Mechanisms, Evaluation, and Management of Chronic Constipation","volume":"158","author":"Bharucha","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2165\/11898640-000000000-00000","article-title":"Laxative abuse: Epidemiology, diagnosis and management","volume":"70","author":"Roerig","year":"2010","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ohkusa, T., Koido, S., Nishikawa, Y., and Sato, N. (2019). Gut Microbiota and Chronic Constipation: A Review and Update. Front. Med., 6.","DOI":"10.3389\/fmed.2019.00019"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/gastro\/goab035","article-title":"Role of gut microbiota in functional constipation","volume":"9","author":"Zhang","year":"2021","journal-title":"Gastroenterol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3945\/an.116.014407","article-title":"Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation","volume":"8","author":"Dimidi","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The Microbiota-Gut-Brain Axis: From Motility to Mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1053\/j.gastro.2016.07.044","article-title":"The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System","volume":"151","author":"Obata","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3945\/ajcn.114.089151","article-title":"The effect of probiotics on functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials","volume":"100","author":"Dimidi","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/19490976.2017.1412908","article-title":"Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: A double-blind, randomized, placebo-controlled, and dose-ranging trial","volume":"9","author":"Ibarra","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1475-2891-13-75","article-title":"Effect of yogurt containing polydextrose, Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019: A randomized, double-blind, controlled study in chronic constipation","volume":"13","author":"Magro","year":"2014","journal-title":"Nutr. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tifs.2018.03.009","article-title":"Postbiotics: An evolving term within the functional foods field","volume":"75","author":"Garcia","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00057-16","DOI":"10.1128\/mSphere.00057-16","article-title":"Culture-Independent Metagenomic Surveillance of Commercially Available Probiotics with High-Throughput Next-Generation Sequencing","volume":"1","author":"Patro","year":"2016","journal-title":"mSphere"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106872","DOI":"10.1016\/j.foodcont.2019.106872","article-title":"Comprehensive approaches for assessing the safety of probiotic bacteria","volume":"108","author":"Pradhan","year":"2020","journal-title":"Food Control"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1128\/AEM.03566-12","article-title":"Genome instability in Lactobacillus rhamnosus GG","volume":"79","author":"Sybesma","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1016\/j.clnu.2022.10.015","article-title":"Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials","volume":"41","author":"Helander","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e074557","DOI":"10.1136\/bmjopen-2023-074557","article-title":"Efficacy in bowel movement and change of gut microbiota on adult functional constipation patients treated with probiotics-containing products: A systematic review and meta-analysis","volume":"14","author":"Ding","year":"2024","journal-title":"BMJ Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/jgh.12168","article-title":"Effects of a probiotic fermented milk on functional constipation: A randomized, double-blind, placebo-controlled study","volume":"28","author":"Mazlyn","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2436888","DOI":"10.1001\/jamanetworkopen.2024.36888","article-title":"Eight-Week Supplementation with Bifidobacterium lactis HN019 and Functional Constipation: A Randomized Clinical Trial","volume":"7","author":"Cheng","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zolkiewicz, J., Marzec, A., Ruszczynski, M., and Feleszko, W. (2020). Postbiotics-A Step Beyond Pre- and Probiotics. Nutrients, 12.","DOI":"10.3390\/nu12082189"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.12938\/bmfh.2022-066","article-title":"Effects of Bifidobacterium longum CLA8013 on bowel movement improvement: A placebo-controlled, randomized, double-blind study","volume":"42","author":"Okada","year":"2023","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.12938\/bmfh.17-025","article-title":"Effects of heat-killed Lactobacillus casei subsp. casei 327 intake on defecation in healthy volunteers: A randomized, double-blind, placebo-controlled, parallel-group study","volume":"37","author":"Saito","year":"2018","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.coph.2019.08.004","article-title":"Focus on the essentials: Tryptophan metabolism and the microbiome-gut-brain axis","volume":"48","author":"Gheorghe","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lin, M.Y., de Zoete, M.R., van Putten, J.P., and Strijbis, K. (2015). Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00554"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.12938\/bmfh.2023-084","article-title":"Activation of chloride channels and promotion of bowel movements by heat-killed Bifidobacterium longum CLA8013","volume":"43","author":"Makizaki","year":"2024","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_31","first-page":"767","article-title":"Heat-Killed Lactobacillus brevis SBC8803 Induces Serotonin Release from Intestinal Cells","volume":"4","author":"Nakaita","year":"2013","journal-title":"Food Nutr. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19376","DOI":"10.1073\/pnas.2000047117","article-title":"Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor","volume":"117","author":"Scott","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12986-023-00739-y","article-title":"Effect of different doses of Lacticaseibacillus paracasei K56 on body fat and metabolic parameters in adult individuals with obesity: A pilot study","volume":"20","author":"Kadeer","year":"2023","journal-title":"Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1007\/s12602-022-09911-x","article-title":"Lacticaseibacillus paracasei K56 Attenuates High-Fat Diet-Induced Obesity by Modulating the Gut Microbiota in Mice","volume":"15","author":"Miao","year":"2023","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_35","first-page":"279","article-title":"Study on Lactobacillus paracasei K56 in regulating intestinal microbiota and promoting laxative function","volume":"41","author":"Liu","year":"2020","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17095","DOI":"10.1038\/nrdp.2017.95","article-title":"Chronic constipation","volume":"3","author":"Camilleri","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1136\/gutjnl-2020-323877","article-title":"Blue poo: Impact of gut transit time on the gut microbiome using a novel marker","volume":"70","author":"Asnicar","year":"2021","journal-title":"Gut"},{"key":"ref_39","first-page":"73","article-title":"Reliability and validity of the Chinese version of the Patient Assessment of Constipation Symptoms questionnaire","volume":"27","author":"Song","year":"2012","journal-title":"J. Nurs. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/BF02056950","article-title":"A constipation scoring system to simplify evaluation and management of constipated patients","volume":"39","author":"Agachan","year":"1996","journal-title":"Dis. Colon Rectum"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1038\/s41598-022-11312-7","article-title":"Evaluation of the Chinese version of the constipation scoring system in Chinese women with pelvic organ prolapse","volume":"12","author":"Liu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_42","first-page":"209","article-title":"Reliability, validity and responsiveness of the Chinese version of the Patient Assessment of Constipation Quality of Life questionnaire","volume":"19","author":"Jin","year":"2011","journal-title":"World Chin. J. Digestol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1016\/j.clnu.2020.01.005","article-title":"Meta-analysis of randomized controlled trials of the effects of probiotics on functional constipation in adults","volume":"39","author":"Zhang","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1038\/ajg.2014.202","article-title":"Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: Systematic review and meta-analysis","volume":"109","author":"Ford","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00255","DOI":"10.14309\/ctg.0000000000000255","article-title":"Impact of Clinical Outcome Measures on Placebo Response Rates in Clinical Trials for Chronic Constipation: A Systematic Review and Meta-analysis","volume":"11","author":"Chen","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1093\/ajcn\/nqac184","article-title":"The Effect of Fiber Supplementation on Chronic Constipation in Adults: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"116","author":"Drysdale","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.sjbs.2015.06.005","article-title":"Milk derived bioactive peptides and their impact on human health-A review","volume":"23","author":"Mohanty","year":"2016","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1034\/j.1600-0773.2003.920601.x","article-title":"The enteric nervous system II: Gastrointestinal functions","volume":"92","author":"Hansen","year":"2003","journal-title":"Pharmacol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Chen, Y.Y., Xu, D.Q., Yue, S.J., Fu, R.J., Yang, J., Xing, L.M., and Tang, Y.P. (2021). Action Mode of Gut Motility, Fluid and Electrolyte Transport in Chronic Constipation. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.630249"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Park, J.W., Kang, M.J., Choi, H.J., Bae, S.J., Choi, Y., Lee, Y.J., Seo, S., Hong, J.T., and Hwang, D.Y. (2019). Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model. Molecules, 24.","DOI":"10.3390\/molecules24050896"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12466","DOI":"10.1590\/1414-431x2023e12466","article-title":"Luteolin ameliorates loperamide-induced functional constipation in mice","volume":"56","author":"Wang","year":"2023","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"883-e234","DOI":"10.1111\/j.1365-2982.2010.01524.x","article-title":"Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow-transit constipation","volume":"22","author":"King","year":"2010","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.copbio.2017.10.007","article-title":"Identification of probiotic effector molecules: Present state and future perspectives","volume":"49","author":"Lebeer","year":"2018","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41538-023-00197-z","article-title":"Untargeted mass spectrometry-based metabolomics approach unveils biochemical changes in compound probiotic fermented milk during fermentation","volume":"7","author":"Sun","year":"2023","journal-title":"npj Sci. Food"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Arslan, B.N., D\u00f6nda\u015f, N.Y., Ko\u00e7han, S., Bulut, S.D., Tamer, M.A., \u00c7elebio\u011flu, H.U., Bodur, M., A\u011fag\u00fcnd\u00fcz, D., Tabanelli, G., and Barbieri, F. (2026). Functional fermented dairy products: A review of mechanisms, health potential, and technological challenges. Front. Nutr., 13.","DOI":"10.3389\/fnut.2026.1779688"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:44:47Z","timestamp":1782967487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":56,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18132114"],"URL":"https:\/\/doi.org\/10.3390\/nu18132114","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}