{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:23:48Z","timestamp":1788996228357,"version":"build-2803163510"},"posted":{"date-parts":[[2025,9,8]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Saccharomyces boulardii<\/jats:italic>\n                  is a widely used probiotic yeast with clinical efficacy against certain gastrointestinal disorders. Although genomically related to\n                  <jats:italic>S. cerevisiae<\/jats:italic>\n                  , the extent to which\n                  <jats:italic>S. boulardii<\/jats:italic>\n                  harbors distinct probiotic-relevant traits remains incompletely defined, particularly across commercially distributed strains. Here, we performed comparative genomic, physiological, and functional analyses of five\n                  <jats:italic>S. boulardii<\/jats:italic>\n                  strains and three\n                  <jats:italic>S. cerevisiae<\/jats:italic>\n                  strains, including baker\u2019s and laboratory variants.\n                  <jats:italic>S. boulardii<\/jats:italic>\n                  strains shared conserved genetic features and exhibited a conserved chromosomal inversion on chromosome XVI, lower copy numbers of CAZyme genes, and lineage-specific amino acid substitutions in central and tryptophan catabolism pathways\u2014potentially underlying elevated production of immunomodulatory metabolites.\n                  <jats:italic>S. boulardii<\/jats:italic>\n                  strains also exhibited enhanced acid tolerance, elevated acetate and succinate production, and robust immunomodulatory activity, including suppression of IL-8 secretion and NF-\u03baB, and consistent activation of the aryl hydrocarbon receptor (AhR) compared to\n                  <jats:italic>S. cerevisiae<\/jats:italic>\n                  . In contrast\n                  <jats:italic>, S. cerevisiae<\/jats:italic>\n                  strains displayed greater bile salt tolerance and faster growth under aerobic and anaerobic conditions at both 30\u00b0C and 37\u00b0C but lacked consistent anti-inflammatory effects or AhR agonism. Metabolic and immunological phenotypes varied with oxygen availability and strain background. Despite high genomic similarity,\n                  <jats:italic>S. cerevisiae<\/jats:italic>\n                  and\n                  <jats:italic>S. boulardii<\/jats:italic>\n                  exhibit distinct functional capacities relevant to probiotic efficacy. These findings help define species- and strain-specific features that inform the development and regulatory evaluation of next-generation yeast probiotics.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    The yeast\n                    <jats:italic>Saccharomyces boulardii<\/jats:italic>\n                    is widely used as a probiotic to support human gut health, yet the reasons behind its beneficial effects remain unclear. This study compares\n                    <jats:italic>S. boulardii<\/jats:italic>\n                    with its close relative,\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    , which is commonly used in baking and research but does not show consistent health benefits. By examining multiple strains, we found that\n                    <jats:italic>S. boulardii<\/jats:italic>\n                    possesses unique features that may explain its ability to survive harsh gut conditions and influence the body\u2019s immune responses. In contrast,\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    grows faster and withstands bile better but lacks the same protective effects. These findings highlight how small genetic and physiological differences between related organisms can lead to distinct impacts on health. Understanding these differences provides a foundation for developing next-generation probiotics and for setting standards in their evaluation and use.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.08.674931","type":"posted-content","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T04:10:26Z","timestamp":1757391026000},"source":"Crossref","is-referenced-by-count":10,"title":["Genomic and phenotypic comparison of\n                  <i>Saccharomyces cerevisiae<\/i>\n                  and\n                  <i>Saccharomyces boulardii<\/i>"],"prefix":"10.64898","author":[{"given":"Hannah Elena","family":"Duffey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0829-2496","authenticated-orcid":false,"given":"Karl Alex","family":"Hedin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitesh P.","family":"Gelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troels Holger","family":"Vaaben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Otto Alexander Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091202001161000_2025.09.08.674931v1.1","doi-asserted-by":"crossref","first-page":"1800421","DOI":"10.1002\/biot.201800421","article-title":"Yeast Systems Biology: Model Organism and Cell Factory","volume":"14","year":"2019","journal-title":"Biotechnol J"},{"key":"2025091202001161000_2025.09.08.674931v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5287.546"},{"key":"2025091202001161000_2025.09.08.674931v1.3","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00025-07"},{"key":"2025091202001161000_2025.09.08.674931v1.4","doi-asserted-by":"publisher","DOI":"10.4161\/bioe.22856"},{"key":"2025091202001161000_2025.09.08.674931v1.5","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.tibtech.2022.03.007","article-title":"Innovation trends in industrial biotechnology","volume":"40","year":"2022","journal-title":"Trends Biotechnol"},{"key":"2025091202001161000_2025.09.08.674931v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2021.10.010"},{"key":"2025091202001161000_2025.09.08.674931v1.7","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.3748\/wjg.v16.i18.2202","article-title":"Systematic review and meta-analysis of Saccharomyces boulardii in adult patients","volume":"16","year":"2010","journal-title":"World Journal of Gastroenterology : WJG"},{"key":"2025091202001161000_2025.09.08.674931v1.8","doi-asserted-by":"publisher","DOI":"10.1139\/w04-050"},{"key":"2025091202001161000_2025.09.08.674931v1.9","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02201-06"},{"key":"2025091202001161000_2025.09.08.674931v1.10","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.ygeno.2020.11.034","article-title":"Transcriptome-wide differences between Saccharomyces cerevisiae and Saccharomyces cerevisiae var. boulardii: Clues on host survival and probiotic activity based on promoter sequence variability","volume":"113","year":"2021","journal-title":"Genomics"},{"key":"2025091202001161000_2025.09.08.674931v1.11","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X11428502"},{"issue":"12","key":"2025091202001161000_2025.09.08.674931v1.12","first-page":"1","article-title":"Effects of broad-spectrum antibiotics on the colonisation of probiotic yeast Saccharomyces boulardii in the murine gastrointestinal tract","volume":"2022","year":"2022","journal-title":"Scientific Reports"},{"key":"2025091202001161000_2025.09.08.674931v1.13","doi-asserted-by":"crossref","unstructured":"McFarland L V . 2017. 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