{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:23:06Z","timestamp":1790878986846,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Science and Technology Special Projects in Henan Province","award":["231100310200"],"award-info":[{"award-number":["231100310200"]}]},{"name":"Major Science and Technology Special Projects in Henan Province","award":["241111314200"],"award-info":[{"award-number":["241111314200"]}]},{"name":"Major Science and Technology Special Projects in Henan Province","award":["221111111400"],"award-info":[{"award-number":["221111111400"]}]},{"name":"Key R&amp;D Projects in Henan Province","award":["231100310200"],"award-info":[{"award-number":["231100310200"]}]},{"name":"Key R&amp;D Projects in Henan Province","award":["241111314200"],"award-info":[{"award-number":["241111314200"]}]},{"name":"Key R&amp;D Projects in Henan Province","award":["221111111400"],"award-info":[{"award-number":["221111111400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Probiotics have attracted increasing attention due to their benefits in terms of relieving gastrointestinal ailments, including constipation. This study evaluated the potential of Weizmannia coagulans BC99 for clinical remission of constipation in adults. In this randomized, double-blind, and placebo-controlled trial, 90 individuals with constipation were divided between a BC99 and a placebo group for an 8-week intervention duration. The spontaneous bowel movement (SBM) frequency, patient assessment of constipation symptoms (PAC-SYM), patient assessment of constipation quality of life (PAC-QOL), inflammatory cytokines, neurotransmitters, and serum metabolites were investigated before and after the intervention. The results showed that BC99 intervention significantly improved constipation symptoms and quality of life in adults with constipation, as evidenced by an increased SBM score and decreased PAC-SYM and PAC-QOL scores. Additionally, BC99 supplementation increased the levels of neurotransmitters (5-HT, MTL, AChE, and BDNF) associated with intestinal motility and alleviated inflammation in participants with constipation, as supported by higher levels of anti-inflammatory factors (IL-4, IL-10) and lower levels of pro-inflammatory factors (IL-6, IFN-\u03b3) in the BC99 group. Furthermore, BC99 altered the abundance of 93 metabolites and affected biological pathways correlated with gastrointestinal motility, including sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism. This study demonstrates the effectiveness of the W. coagulans BC99 strain in relieving constipation in adults, and reveals its potential mechanism of action. These findings provide a scientific basis for BC99 as an effective and safe probiotic for constipation treatment.<\/jats:p>","DOI":"10.3390\/foods14040654","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T11:31:17Z","timestamp":1739791877000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Weizmannia coagulans BC99 Relieves Constipation Symptoms by Regulating Inflammatory, Neurotransmitter, and Lipid Metabolic Pathways: A Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"14","author":[{"given":"Qiuxia","family":"Fan","sequence":"first","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"},{"name":"Henan Engineering Research Center of Food Material, Henan University of Science and Technology, Luoyang 471023, China"},{"name":"Henan Engineering Research Center of Food Microbiology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyin","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Wecare Probiotics Co., Ltd., Suzhou 215200, China"},{"name":"Germline Stem Cells and Microenvironment Lab, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghui","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Wecare Probiotics Co., Ltd., Suzhou 215200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"},{"name":"Henan Engineering Research Center of Food Material, Henan University of Science and Technology, Luoyang 471023, China"},{"name":"Henan Engineering Research Center of Food Microbiology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Wecare Probiotics Co., Ltd., Suzhou 215200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-0318","authenticated-orcid":false,"given":"Shaobin","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471000, China"},{"name":"Henan Engineering Research Center of Food Material, Henan University of Science and Technology, Luoyang 471023, China"},{"name":"Henan Engineering Research Center of Food Microbiology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Feng, C., Gao, G., Wu, K., and Weng, X. (2024). Causal relationship between gut microbiota and constipation: A bidirectional Mendelian randomization study. Front. Microbiol., 192.","DOI":"10.3389\/fmicb.2024.1438778"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"106755","DOI":"10.1016\/j.phrs.2023.106755","article-title":"Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study","volume":"191","author":"Ma","year":"2023","journal-title":"Pharmacol. Res."},{"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":"12","DOI":"10.1016\/j.jocn.2024.05.030","article-title":"Association between sleep disorders and constipation Risk: A systematic review and Meta-Analysis","volume":"126","author":"Tian","year":"2024","journal-title":"J. Clin. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/jch.13489","article-title":"Constipation-induced pressor effects as triggers for cardiovascular events","volume":"21","author":"Ishiyama","year":"2019","journal-title":"J. Clin. Hyperten."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/BF01308169","article-title":"Association of constipation with neurologic diseases","volume":"37","author":"Johanson","year":"1992","journal-title":"Digest. Dis. Sci."},{"key":"ref_8","first-page":"43","article-title":"Step on the accelerator: Modern treatment of constipation","volume":"40","author":"Staursky","year":"2024","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, Y., Shi, J., Luo, X., Luo, S., Peter, C.K., Cheung, H.C., Yang, Q., and Zhang, B. (2024). How do probiotics alleviate constipation? A narrative review of mechanisms. Crit. Rev. Biotechnol., 45.","DOI":"10.1080\/07388551.2024.2336531"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, P., Kong, L., Huang, H., Pan, Y., Zhang, D., Jiang, J., Shen, Y., Xi, C., Lai, J., and Ng, C.H. (2022). Gut Microbiota\u2014A Potential Contributor in the Pathogenesis of Bipolar Disorder. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.830748"},{"key":"ref_12","first-page":"218","article-title":"American Gastroenterological Association Technical Review on Constipation","volume":"144","author":"Bharucha","year":"2013","journal-title":"Gas. Troenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2197837","DOI":"10.1080\/19490976.2023.2197837","article-title":"Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: A double-blinded randomized placebo trial","volume":"15","author":"Lai","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"A\u011fag\u00fcnd\u00fcz, D., Cocozza, E., and Cemali, \u00d6. (2023). Understanding the role of the gut microbiome in gastrointestinal cancer: A review. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1130562"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Makizaki, Y., Uemoto, T., and Yokota, H. (2022). Improvement of loperamide-induced slow transit constipation by Biffdobacterium biffdum G9-1 is mediated by the correction of butyrate production and neurotransmitter proffle due to improvement in dysbiosis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267927"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Konuray, G., and Erginkaya, Z. (2018). Potential use of Bacillus coagulans in the food industry. Foods, 7.","DOI":"10.3390\/foods7060092"},{"key":"ref_17","first-page":"e00449-23","article-title":"Complete genome sequence of Heyndrickxia (Bacillus) coagulans BC99 isolated from a fecal sample of a healthy infant","volume":"13","author":"Zhu","year":"2024","journal-title":"Microbiol. Resour."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zeng, Z., Xu, Y., Ying, J., Wang, B., and Majeed, M. (2020). Application of Bacillus coagulans in animal husbandry and its underlying mechanisms. Animals, 10.","DOI":"10.3390\/ani10030454"},{"key":"ref_19","first-page":"16","article-title":"Weizmannia coagulans: An ideal probiotic for gut health","volume":"13","author":"Zhang","year":"2023","journal-title":"Food Sci. Hum. Well."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s12602-019-09542-9","article-title":"Bacillus coagulans Unique IS2 in Constipation: A Double-Blind, Placebo-Controlled Study","volume":"12","author":"Madempudi","year":"2020","journal-title":"Probiotics Antimicro."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, Y., Bai, Z., Jin, Y., Zhu, H., Dong, Y., Gu, S., and Jin, Y. (2024). A randomized, double-blind, placebo-controlled clinical study to evaluate the efffcacy and safety of Weizmannia coagulans BC99 in the treatment of chronic constipation in adults. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1395083"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luo, M., Xie, P., Deng, X., Fan, J., and Xiong, L. (2023). Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites. Nutrients, 15.","DOI":"10.3390\/nu15214502"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1038\/s41430-022-01189-0","article-title":"The effect of multistrain probiotics on functional constipation in the elderly: A randomized controlled trial","volume":"76","author":"Mucalo","year":"2022","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"skab137","DOI":"10.1093\/jas\/skab137","article-title":"Evaluation of graded levels of Bacillus coagulans GBI-30, 6086 on apparent nutrient digestibility, stool quality, and intestinal health indicators in healthy adult dogs","volume":"99","author":"Acuff","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110569","DOI":"10.1016\/j.foodres.2021.110569","article-title":"Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function","volume":"147","author":"Yang","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_26","first-page":"585","article-title":"Clinical assessment and cytokines level in constipation-predominant irritable bowel syndrome participants treated with Lactobacillus-containing cultured milk drink","volume":"84","author":"Mokhtar","year":"2021","journal-title":"Acta Gastroenterol. Belg."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Choi, Y.J., Song, H.J., Kim, J.E., Lee, S.J., Jin, Y.J., Roh, Y.J., Seol, A., Kim, H.S., and Hwang, D.Y. (2022). Dysregulation of the Enteric Nervous System in the Mid Colon of Complement Component 3 Knockout Mice with Constipation Phenotypes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126862"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"111882","DOI":"10.1016\/j.exger.2022.111882","article-title":"Comprehensive 16S rRNA sequencing based microbiomes and H NMR based metabolomics reveal the relationships of aging and constipation","volume":"166","author":"Liu","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.18632\/aging.202526","article-title":"The impact of visceral obesity on chronic constipation, inflammation, immune function and cognitive function in patients with inflammatory bowel disease","volume":"13","author":"Wan","year":"2021","journal-title":"Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11025","DOI":"10.3168\/jds.2020-18639","article-title":"Fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis ssp. lactis V9 alleviated constipation symptoms through regulation of intestinal microbiota, inflammation, and metabolic pathways","volume":"103","author":"Wang","year":"2020","journal-title":"J. Dairy. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Park, S.-A., Lee, G.-H., Hoang, T.-H., Lee, H.-Y., Kang, I.-Y., Chung, M.-J., Jin, J.-S., and Chae, H.-J. (2021). Heat-inactivated Lactobacillus plantarum nF1 promotes intestinal health in Loperamide-induced constipation rats. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250354"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, T., Lu, J., Qin, J., Chen, Y., Shi, Z., Wei, W., Xiong, P., Ma, D., and Song, X. (2023). Altered intestinal barrier contributes to cognitive impairment in old mice with constipation after sevoflurane anesthesia. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1117028"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/mp.2011.85","article-title":"Genome-wide association studies establish that human intelligence is highly heritable and polygenic","volume":"16","author":"Davies","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.3748\/wjg.v26.i14.1564","article-title":"Intestinal epithelial barrier and neuromuscular compartment in health and disease","volume":"26","author":"Pellegrini","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xiao, L., Liu, Q., Luo, M., and Xiong, L. (2021). Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.729346"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3892\/etm.2023.11898","article-title":"Arctiin alleviates functional constipation by enhancing intestinal motility in mice","volume":"25","author":"Wang","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"ref_38","first-page":"2165","article-title":"Enteric glia mediate neuronal outgrowth through release of neurotrophic factors","volume":"7","author":"Hansebout","year":"2012","journal-title":"Neural. Regen. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"McGowan, E.M., Lin, Y., and Chen, S. (2022). Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway. Cancers, 14.","DOI":"10.3390\/cancers14030535"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2147\/CEG.S43453","article-title":"S1pping fire: Sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer","volume":"7","author":"Saba","year":"2014","journal-title":"Clin. Exp. Gastroenter."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, C.Z., Wu, L.M., Zhu, C.X., Du, H.Y., Chen, G.X., and Yang, F. (2024). The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1363077"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kato, S., Takahashi, A., Shindo, M., Yoshida, A., Kawamura, T., Matsumoto, K., and Matsuura, B. (2019). Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0205939"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhao, X., Wang, L., and Quan, L. (2023). Association between dietary phosphorus intake and chronic constipation in adults: Evidence from the National Health and Nutrition Examination Survey. BMC Gastroenterol., 23.","DOI":"10.1186\/s12876-022-02629-8"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/4\/654\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:34:59Z","timestamp":1760027699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/4\/654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,15]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["foods14040654"],"URL":"https:\/\/doi.org\/10.3390\/foods14040654","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,15]]}}}