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However, the underlying mechanisms of the microbiome heterogeneity and its regulation on epithelial function such as intestinal stem cell (ISC) fate remain unclear. Employing pigs of genetically distinct breeds (obese Meishan and lean Yorkshire), this study reveals transcriptome\u2010wide variations in microbial ecology of the jejunum, characterized by enrichment of active\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    species, notably the predominant\n                    <jats:italic>Lactobacillus amylovorus<\/jats:italic>\n                    (\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    ), and lactate metabolism network in obese breeds. The\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    \u2010dominant heterogeneity is paralleled with epithelial functionality difference as reflected by highly expressed GPR81, more proliferative ISCs and activated Wnt\/\u03b2\u2010catenin signaling. Experiments using in\u2010house developed porcine jejunal organoids prove that live\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    and its metabolite lactate promote intestinal organoid growth. Mechanistically,\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    and lactate activate Wnt\/\u03b2\u2010catenin signaling in a GPR81\u2010dependent manner to promote ISC\u2010mediated epithelial proliferation. However, heat\u2010killed\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    fail to cause these changes. These findings uncover a previously underrepresented role of\n                    <jats:italic>L. amylovorus<\/jats:italic>\n                    in regulating jejunal stem cells via\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    \u2010lactate\u2010GPR81 axis, a key mechanism bridging breed\u2010driven intestinal microbiome heterogeneity with ISC fate. Thus, results from this study provide new insights into the role of gut microbiome and stem cell interactions in maintaining intestinal homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202400058","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T01:46:45Z","timestamp":1719539205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Breed\u2010Driven Microbiome Heterogeneity Regulates Intestinal Stem Cell Proliferation via\n                    <i>Lactobacillus<\/i>\n                    \u2010Lactate\u2010GPR81 Signaling"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1279-9794","authenticated-orcid":false,"given":"Haiqin","family":"Wu","sequence":"first","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and 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