{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T03:24:25Z","timestamp":1787369065883,"version":"build-2736575974"},"reference-count":59,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Benef. Microbes"],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Synbiotics exert various physiological effects by complementing the physiological functions of both probiotics and prebiotics. Chronic constipation is a prevalent global health concern, and despite several clinical studies utilising synbiotics, definitive conclusions regarding its efficacy remain elusive. This study aimed to investigate the effect of a synbiotic combination of\n                    <jats:italic>Lacticaseibacillus paracasei<\/jats:italic>\n                    strain Shirota (LcS: formerly known as\n                    <jats:italic>Lactobacillus casei<\/jats:italic>\n                    strain Shirota) and galactooligosaccharides (GOS), both of which independently improve defecation symptoms, on defecation frequency in constipation-prone healthy Japanese adults. This study employed a placebo-controlled, randomised, double-blind, parallel-group comparison design over a 4-week consecutive intake period. The primary objective was to evaluate the efficacy of the synbiotic intervention on bowel movement frequency in healthy adults prone to constipation. The synbiotic group exhibited a significantly increased defecation frequency at week 2 (\n                    <jats:inline-formula\/>\n                    ) but not at week 4, whereas the number of defecation days showed only a trend at week 2 (\n                    <jats:inline-formula\/>\n                    ). This represents a key limitation of this study. A significant positive correlation was observed between faecal LcS counts and defecation parameters in the synbiotic group, with no equivalent correlation observed for endogenous\n                    <jats:italic>Lactobacillaceae<\/jats:italic>\n                    in either group. This suggests a strain-specific effect of LcS beyond a general class effect of\n                    <jats:italic>Lactobacillaceae<\/jats:italic>\n                    . Additionally, increases in faecal\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    counts and a decrease in isobutyric and isovaleric acid levels were observed along with improvements in defecation-related symptoms. These findings suggest that the combination of LcS and GOS may contribute to improvements in constipation-related outcomes in healthy individuals prone to constipation.\n                  <\/jats:p>\n                  <jats:p>The study was registered by the University Hospital Medical Information Network: registration number: UMIN000039236.<\/jats:p>","DOI":"10.1163\/18762891-bja00134","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T03:04:01Z","timestamp":1787367841000},"page":"1-15","source":"Crossref","is-referenced-by-count":0,"title":["Improvement effect of synbiotics intake on stool frequency in constipation-prone healthy participants: placebo-controlled, randomised, double-blind, parallel-group comparison"],"prefix":"10.1163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2899-0339","authenticated-orcid":true,"given":"T.","family":"Shima","sequence":"first","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kaga","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3272-3070","authenticated-orcid":true,"given":"Y.","family":"Kado","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Date","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Shimamoto","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Tajima","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-8267","authenticated-orcid":true,"given":"H.","family":"Makino","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Katto","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Kato","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-6447","authenticated-orcid":true,"given":"H.","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Yakult Central Institute, 5-11 Izumi, Kunitachi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"issue":"1","key":"R000001","series-title":"Alimentary Pharmacology and Therapeutics","first-page":"104","article-title":"Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation","volume":"29","author":"Agrawal, A.","unstructured":"Agrawal, A., Houghton, L.A., Morris, J., Reilly, B., Guyonnet, D., Feuillerat, N.G., Schlumberger, A., Jakob, S. and Whorwell, P.J., 2009. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Alimentary Pharmacology and Therapeutics 29(1): 104-114. https:\/\/doi.org\/10.1111\/j.1365-2036.2008.03853.x"},{"issue":"1","key":"R000002","series-title":"Gut Microbes","article-title":"A double-blind, 377-subject randomized study identifies","volume":"13","author":"Azcarate-Peril, M.A.","unstructured":"Azcarate-Peril, M.A., Roach, J., Marsh, A., Chey, W.D., Sandborn, W.J., Ritter, A.J., Savaiano, D.A. and Klaenhammer, T.R., 2021. A double-blind, 377-subject randomized study identifies. Gut Microbes 13(1): 1957536. https:\/\/doi.org\/10.1080\/19490976.2021.1957536"},{"issue":"1","key":"R000003","series-title":"mBio","article-title":"Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers","volume":"10","author":"Baxter, N.T.","unstructured":"Baxter, N.T., Schmidt, A.W., Venkataraman, A., Kim, K.S., Waldron, C. and Schmidt, T.M., 2019. Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers. mBio 10(1): e02566-18. https:\/\/doi.org\/10.1128\/mBio.02566-18"},{"issue":"3","key":"R000004","series-title":"European Journal of Clinical Nutrition","first-page":"355","article-title":"Impact of consuming a milk drink containing a probiotic on mood and cognition","volume":"61","author":"Benton, D.","unstructured":"Benton, D., Williams, C. and Brown, A., 2007. Impact of consuming a milk drink containing a probiotic on mood and cognition. European Journal of Clinical Nutrition 61(3): 355-361. https:\/\/doi.org\/10.1038\/sj.ejcn.1602546"},{"issue":"8","key":"R000005","series-title":"Nature Biotechnology","first-page":"852","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen, E.","unstructured":"Bolyen, E., Rideout, J.R., Dillon, M.R., Bokulich, N.A., Abnet, C.C., Al-Ghalith, G.A., Alexander, H., Alm, E.J., Arumugam, M., Asnicar, F., Bai, Y., Bisanz, J.E., Bittinger, K., Brejnrod, A., Brislawn, C.J., Brown, C.T., Callahan, B.J., Caraballo-Rodr\u0131\u0301guez, A.M., Chase, J., Cope, E.K., Da Silva, R., Diener, C., Dorrestein, P.C., Douglas, G.M., Durall, D.M., Duvallet, C., Edwardson, C.F., Ernst, M., Estaki, M., Fouquier, J., Gauglitz, J.M., Gibbons, S.M., Gibson, D.L., Gonzalez, A., Gorlick, K., Guo, J., Hillmann, B., Holmes, S., Holste, H., Huttenhower, C., Huttley, G.A., Janssen, S., Jarmusch, A.K., Jiang, L., Kaehler, B.D., Kang, K.B., Keefe, C.R., Keim, P., Kelley, S.T., Knights, D., Koester, I., Kosciolek, T., Kreps, J., Langille, M.G.I., Lee, J., Ley, R., Liu, Y.X., Loftfield, E., Lozupone, C., Maher, M., Marotz, C., Martin, B.D., McDonald, D., McIver, L.J., Melnik, A.V., Metcalf, J.L., Morgan, S.C., Morton, J.T., Naimey, A.T., Navas-Molina, J.A., Nothias, L.F., Orchanian, S.B., Pearson, T., Peoples, S.L., Petras, D., Preuss, M.L., Pruesse, E., Rasmussen, L.B., Rivers, A., Robeson, M.S., Rosenthal, P., Segata, N., Shaffer, M., Shiffer, A., Sinha, R., Song, S.J., Spear, J.R., Swafford, A.D., Thompson, L.R., Torres, P.J., Trinh, P., Tripathi, A., Turnbaugh, P.J., Ul-Hasan, S., van\u00a0der Hooft, J.J.J., Vargas, F., Va\u0301zquez-Baeza, Y., Vogtmann, E., von Hippel, M., Walters, W., Wan, Y., Wang, M., Warren, J., Weber, K.C., Williamson, C.H.D., Willis, A.D., Xu, Z.Z., Zaneveld, J.R., Zhang, Y., Zhu, Q., Knight, R. and Caporaso, J.G., 2019. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology 37(8): 852-857. https:\/\/doi.org\/10.1038\/s41587-019-0209-9"},{"issue":"7","key":"R000006","series-title":"Nature Methods","first-page":"581","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan, B.J.","unstructured":"Callahan, B.J., McMurdie, P.J., Rosen, M.J., Han, A.W., Johnson, A.J.A. and Holmes, S.P., 2016. DADA2: High-resolution sample inference from Illumina amplicon data. Nature Methods 13(7): 581-583. https:\/\/doi.org\/10.1038\/nmeth.3869"},{"issue":"8","key":"R000007","series-title":"ISME Journal","first-page":"1621","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso, J.G.","unstructured":"Caporaso, J.G., Lauber, C.L., Walters, W.A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S.M., Betley, J., Fraser, L., Bauer, M., Gormley, N., Gilbert, J.A., Smith, G. and Knight, R., 2012. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. 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PLoS ONE 6(9): e25200. https:\/\/doi.org\/10.1371\/journal.pone.0025200"},{"issue":"1-2","key":"R000011","series-title":"International Journal of Microbiology","first-page":"210","article-title":"Identification and quantification of Lactobacillus casei strain Shirota in human feces with strain-specific primers derived from randomly amplified polymorphic DNA","volume":"126","author":"Fujimoto, J.","unstructured":"Fujimoto, J., Matsuki, T., Sasamoto, M., Tomii, Y. and Watanabe, K., 2008. Identification and quantification of Lactobacillus casei strain Shirota in human feces with strain-specific primers derived from randomly amplified polymorphic DNA. 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Bioscience of Microbiota, Food and Health 40(2): 105-114. https:\/\/doi.org\/10.12938\/bmfh.2020-073"},{"issue":"6","key":"R000013","series-title":"Journal of Nutrition","first-page":"1401","article-title":"Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics","volume":"125","author":"Gibson, G.R.","unstructured":"Gibson, G.R. and Roberfroid, M., 1995. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. Journal of Nutrition 125(6): 1401-1412. https:\/\/doi.org\/10.1093\/jn\/125.6.1401"},{"issue":"1","key":"R000014","series-title":"American Journal of Physiology \u2013 Gastrointestinal and Liver Physiology","first-page":"G429","article-title":"The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF","volume":"292","author":"Grider, J.R.","unstructured":"Grider, J.R. and Piland, B.E., 2007. 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Anaerobe 33: 33-41. https:\/\/doi.org\/10.1016\/j.anaerobe.2015.01.005"},{"key":"R000019","series-title":"Chromatography","first-page":"9","article-title":"Simultaneous analysis of glucuronyl- and sulpho-conjugates of intestinal putrefactive compounds in human urine by ultra-performance liquid chromatography tandem mass spectrometry","volume":"40","author":"Kawase, T.","unstructured":"Kawase, T., Kawakami, T., Harada, K. and Chonan, O., 2019. Simultaneous analysis of glucuronyl- and sulpho-conjugates of intestinal putrefactive compounds in human urine by ultra-performance liquid chromatography tandem mass spectrometry. 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Effect of Lactobacillus casei Shirota on colonic transit time in patients with chronic constipation. Coloproctology 33: 109-113."},{"issue":"1","key":"R000022","series-title":"Microbiome","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, J.A.","unstructured":"Krumbeck, J.A., Rasmussen, H.E., Hutkins, R.W., Clarke, J., Shawron, K., Keshavarzian, A. and Walter, J., 2018. Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics. Microbiome 6(1): 121. https:\/\/doi.org\/10.1186\/s40168-018-0494-4"},{"issue":"16","key":"R000023","series-title":"Applied and Environmental Microbiology","first-page":"5440","article-title":"Detection of human intestinal catalase-negative, gram-positive cocci by rRNA-targeted reverse transcription-PCR","volume":"76","author":"Kubota, H.","unstructured":"Kubota, H., Tsuji, H., Matsuda, K., Kurakawa, T., Asahara, T. and Nomoto, K., 2010. Detection of human intestinal catalase-negative, gram-positive cocci by rRNA-targeted reverse transcription-PCR. Applied and Environmental Microbiology 76(16): 5440-5451. https:\/\/doi.org\/10.1128\/AEM.03132-09"},{"issue":"1","key":"R000024","series-title":"Nutrients","article-title":"Lactobacillus reuteri DSM 17938 and magnesium oxide in children with functional chronic constipation: a double-blind and randomized clinical trial","volume":"12","author":"Kubota, M.","unstructured":"Kubota, M., Ito, K., Tomimoto, K., Kanazaki, M., Tsukiyama, K., Kubota, A., Kuroki, H., Fujita, M. and Vandenplas, Y., 2020. Lactobacillus reuteri DSM 17938 and magnesium oxide in children with functional chronic constipation: a double-blind and randomized clinical trial. Nutrients 12(1): 225 https:\/\/doi.org\/10.3390\/nu12010225"},{"issue":"12","key":"R000025","series-title":"Food and Function","first-page":"6374","article-title":"Efficacy and safety of galacto-oligosaccharide in the treatment of functional constipation: randomized clinical trial","volume":"15","author":"Lee, J.H.","unstructured":"Lee, J.H., Kim, G.B., Han, K., Jung, E.-J., Suh, H.J. and Jo, K., 2024. Efficacy and safety of galacto-oligosaccharide in the treatment of functional constipation: randomized clinical trial. Food and Function 15(12): 6374-6382. https:\/\/doi.org\/10.1039\/d4fo00999a"},{"issue":"6","key":"R000026","series-title":"Microbiology","first-page":"1647","article-title":"Protein degradation by human intestinal bacteria","volume":"132","author":"Macfarlane, G.T.","unstructured":"Macfarlane, G.T., Cummings, J.H. and Allison, C., 1986. Protein degradation by human intestinal bacteria. 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Applied and Environmental Microbiology 70(1): 167-173. https:\/\/doi.org\/10.1128\/AEM.70.1.167-173.2004"},{"issue":"4","key":"R000029","series-title":"Beneficial Microbes","first-page":"453","article-title":"Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants","volume":"7","author":"Matsuki, T.","unstructured":"Matsuki, T., Tajima, S., Hara, T., Yahagi, K., Ogawa, E. and Kodama, H., 2016. Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants. Beneficial Microbes 7(4): 453-461. https:\/\/doi.org\/10.3920\/BM2015.0168"},{"issue":"1","key":"R000030","series-title":"Journal of Intestinal Microbiology","first-page":"25","article-title":"Effects of transgalactosylated oligosaccharides mixture (N-GOS) on human intestinal microflora","volume":"18","author":"Matsumoto, K.","unstructured":"Matsumoto, K., Takada, T., Yuki, N., Kawakami, K., Sakai, T., Nomoto, K., Kimura, K., Matsumoto, K. and Iino, H., 2004. Effects of transgalactosylated oligosaccharides mixture (N-GOS) on human intestinal microflora. 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