{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:12:57Z","timestamp":1791918777060,"version":"4.3.4"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seed Health, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Bloating, gas, and abdominal discomfort are common in healthy individuals but lack effective interventions. Probiotics can alleviate some gastrointestinal (GI) symptoms; however, evidence for their impact on bloating, gas and abdominal discomfort in otherwise healthy populations remains limited. Mechanistic studies suggest that synbiotics may influence the underlying mechanisms of bloating, including increased gas production, impaired gut motility, and visceral hypersensitivity, but there is a paucity of data from large trials evaluating clinical outcomes. Accordingly, we evaluated the effects of a multi-species synbiotic on GI symptoms. Methods: In a randomized, double-blind, placebo-controlled, decentralized trial, participants (n = 350) with self-reported bloating\/indigestion received either a multi-species synbiotic (53.6 billion AFU multi-species probiotic and 400 mg pomegranate extract; DS-01) or placebo daily for 6 weeks. Outcomes included GI quality-of-life (DQLQ), bloating and gas (PROMIS-GI 13a), abdominal discomfort (PROMIS-GI 5a), constipation, regularity, mood-related symptoms, and safety. Results: The multi-species synbiotic improved GI quality-of-life compared to placebo (0.80 vs. 1.20; p &lt; 0.05) at Week 6. Bloating and gas were reduced in the synbiotic arm compared to placebo (16.0 vs. 21.0; p &lt; 0.01), with more participants reporting never\/rarely bloating (72.3% vs. 55.9%; p &lt; 0.001). Abdominal discomfort also decreased (8.0 vs. 10.0; p &lt; 0.01). Additionally, there was a statistically significant improvement in constipation symptoms and regularity in the synbiotic arm relative to placebo. Conclusions: Daily supplementation with this multi-species synbiotic significantly improved GI quality-of-life, bloating, gas, abdominal discomfort, and bowel habits. This is the first synbiotic to demonstrate meaningful improvements in bloating and gas in a generally healthy, diverse, real-world population.<\/jats:p>","DOI":"10.3390\/nu18020255","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:03:10Z","timestamp":1768381390000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Randomized, Placebo-Controlled Trial Evaluating Multi-Species Synbiotic Supplementation for Bloating, Gas, and Abdominal Discomfort"],"prefix":"10.3390","volume":"18","author":[{"given":"Jessica R.","family":"Allegretti","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain","family":"Kassam","sequence":"additional","affiliation":[{"name":"Seed Health, Inc., Venice, CA 90291, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen R.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Grinspan","sequence":"additional","affiliation":[{"name":"The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najwa","family":"El-Nachef","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of California, San Francisco, CA 94143, USA"},{"name":"Division of Gastroenterology, Henry Ford Health System, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Van Den Elzen","sequence":"additional","affiliation":[{"name":"Seed Health, Inc., Venice, CA 90291, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7345-9635","authenticated-orcid":false,"given":"Ralf","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Increnovo LLC, Whitefish Bay, WI 53217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Feuerstadt","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Gastroenterology, PACT Gastroenterology Center, Hamden, CT 06518, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1053\/j.gastro.2023.05.049","article-title":"Prevalence and Associated Factors of Bloating: Results from the Rome Foundation Global Epidemiology Study","volume":"165","author":"Ballou","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/j.cgh.2022.10.031","article-title":"Abdominal Bloating in the United States: Results of a Survey of 88,795 Americans Examining Prevalence and Healthcare Seeking","volume":"21","author":"Oh","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e70076","DOI":"10.1111\/nmo.70076","article-title":"Gas-Related Symptoms in the General Population: Prevalence, Impact and Associated Factors in a Survey of the United States, the United Kingdom, and Mexico","volume":"20","author":"Palsson","year":"2025","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mej\u00eda-Caballero, A., and Marco, M.L. (2025). Lactobacilli biology, applications and host interactions. Nat. Rev. Microbiol., Online ahead of print.","DOI":"10.1038\/s41579-025-01205-7"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"O\u2019Callaghan, A., and van Sinderen, D. (2016). Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00925"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1017\/gmb.2023.18","article-title":"Megasphaera elsdenii, a commensal member of the gut microbiota, is associated with elevated gas production during in vitro fermentation","volume":"5","author":"Mutuyemungu","year":"2023","journal-title":"Gut Microbiome"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1053\/j.gastro.2010.01.053","article-title":"Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats","volume":"138","author":"Soret","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zheng, Z., Tang, J., Hu, Y., and Zhang, W. (2022). Role of gut microbiota-derived signals in the regulation of gastrointestinal motility. Front. Med., 9.","DOI":"10.3389\/fmed.2022.961703"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pain.2009.06.017","article-title":"Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome","volume":"146","author":"Zhou","year":"2009","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15706","DOI":"10.1038\/s41598-024-65791-x","article-title":"Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis","volume":"14","author":"Yasuda","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1053\/j.gastro.2023.07.018","article-title":"Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis","volume":"165","author":"Goodoory","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/ajg.2016.511","article-title":"Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Benefit of the Probiotic Bifidobacterium infantis 35624 in Non-Patients with Symptoms of Abdominal Discomfort and Bloating","volume":"112","author":"McRorie","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2007.10.001","article-title":"Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: A double-blind, placebo-controlled, randomized trial","volume":"28","author":"Diop","year":"2008","journal-title":"Nutr. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s40168-018-0494-4","article-title":"Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics","volume":"6","author":"Krumbeck","year":"2018","journal-title":"Microbiome"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Napier, B.A., Allegretti, J.R., Feuerstadt, P., Kelly, C.R., Van Hise, N.W., J\u00e4ger, R., Kassam, Z., and Reid, G. (2025). Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial. Nutrients, 17.","DOI":"10.3390\/nu17172734"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e0188022","DOI":"10.1128\/aem.01880-22","article-title":"Capacity of a Microbial Synbiotic To Rescue the In Vitro Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics","volume":"89","author":"Tierney","year":"2023","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.amepre.2010.10.009","article-title":"Starting the conversation performance of a brief dietary assessment and intervention tool for health professionals","volume":"40","author":"Paxton","year":"2011","journal-title":"Am. J. Prev. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1097\/MCG.0b013e3181ee31c3","article-title":"The use of probiotics in healthy volunteers with evacuation disorders and hard stools: A double-blind, randomized, placebo-controlled study","volume":"44","author":"Carmagnola","year":"2010","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12955-022-01956-4","article-title":"Validation of a novel quality of life questionnaire: The Digestion-associated Quality of Life Questionnaire (DQLQ)","volume":"20","author":"Beke","year":"2022","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1038\/ajg.2014.237","article-title":"Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) gastrointestinal symptom scales","volume":"109","author":"Spiegel","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1111\/j.1572-0241.2006.00734.x","article-title":"Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome","volume":"101","author":"Whorwell","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2409682","DOI":"10.1080\/15502783.2024.2409682","article-title":"The effects of AG1\u00ae supplementation on the gut microbiome of healthy adults: A randomized, double-blind, placebo-controlled clinical trial","volume":"21","author":"Raub","year":"2024","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"de Wouters d\u2019Oplinter, A., Huwart, S.J.P., Cani, P.D., and Everard, A. (2022). Gut microbes and food reward: From the gut to the brain. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.947240"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kalman, D.S., Schwartz, H.I., Alvarez, P., Feldman, S., Pezzullo, J.C., and Krieger, D.R. (2009). A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms. BMC Gastroenterol., 9.","DOI":"10.1186\/1471-230X-9-85"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"952-e76","DOI":"10.1111\/j.1365-2982.2009.01324.x","article-title":"The effects of butyrate enemas on visceral perception in healthy volunteers","volume":"21","author":"Vanhoutvin","year":"2009","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"387","DOI":"10.15403\/jgld.2014.1121.234.elr","article-title":"The effect of Lactobacillus reuteri supplementation in adults with chronic functional constipation: A randomized, double-blind, placebo-controlled trial","volume":"23","author":"Ojetti","year":"2014","journal-title":"J. Gastrointestin Liver Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41598-019-48554-x","article-title":"Randomized clinical trial: The effect of probiotic Bacillus coagulans Unique IS2 vs. placebo on the symptoms management of irritable bowel syndrome in adults","volume":"9","author":"Madempudi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s12944-024-02203-z","article-title":"Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: A double-blind randomized controlled trial","volume":"23","author":"Firoozi","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e081123","DOI":"10.1136\/bmj-2024-081123","article-title":"CONSORT 2025 Statement: Updated guideline for reporting randomised trials","volume":"388","author":"Hopewell","year":"2025","journal-title":"BMJ"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:15:15Z","timestamp":1768382115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18020255"],"URL":"https:\/\/doi.org\/10.3390\/nu18020255","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}