{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:35:59Z","timestamp":1781624159272,"version":"3.54.5"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized,\u00a0placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sixty-four children (3\u201317 years of age) were randomized to receive a synbiotic (<jats:italic>n<\/jats:italic>\u2009=\u200933) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (<jats:italic>n<\/jats:italic>\u2009=\u200931) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Treatment increased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (<jats:italic>p<\/jats:italic>\u2009=\u20090.00074).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Impact<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Intervention induced an increased abundance of bifidobacteria in children, compared to placebo.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41390-022-02289-0","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:02:28Z","timestamp":1667347348000},"page":"2005-2013","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial"],"prefix":"10.1038","volume":"93","author":[{"given":"Braden T.","family":"Tierney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Versalovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Petrosino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P.","family":"Chumpitazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeran A.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Boetes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Smits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanthi G.","family":"Parkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Voreades","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ece","family":"Kartal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Al-Ghalith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Bron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Dhir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"2289_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18871-1","volume":"11","author":"O Manor","year":"2020","unstructured":"Manor, O. et al. 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R.D. is a co-founder and CEO of Seed Health (SH) and Luca Biologics.\u00a0J.V., A.F., E.A.M., C.E.M., and J.F.P. are members of the SH\u00a0 Scientific board. SH Scientific board members and employees hold equity positions in SH\u00a0unless otherwise stated.\u00a0B.T.T., G.S., N.V., P.A.B., G.R., and E.K. are consultants for SH and were not involved in the microbial synbiotic or clinical trial design. B.T.T. additionally consults for Enzymetrics Bioscience and holds an equity position in SH.\u00a0S.G.P. and G.A.G.\u00a0are employed by SH and were\u00a0not involved in microbial synbiotic or clinical trial design.\u00a0B.P.C. receives potential royalties from the Rome Foundation for the usage of the modified Bristol Stool Form Scale for Children, which is not used in this study. A.F. is additionally a cofounder and stockholder of Alba Therapeutics, a company developing treatments complementary to the gluten-free diet by exploiting gut permeability. E.A.M. is additionally on the Scientific Advisory Board of Axial Biotherapeutics, Pendulum Therapeutics, Bloom Science, Mahana Therapeutics, APC Ireland, Danone, and Amare. J.F.P. is the Founder and Chief Scientific Officer of Diversigen, Inc. and is on the Scientific Advisory Board for 4D Pharma, PLC. C.E.M. is cofounder of Biotia and Onegevity Health.\u00a0J.V. is\u00a0on the scientific advisory boards for Biomica and Plexus Worldwide.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Patient consent was required and received for this clinical trial and publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}