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However, the interaction of the TLR4 with colonizing bacteria in intestinal development is incompletely understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>An established human immature small intestinal cell line, human fetal intestinal organoids, and wild-type (WT) and TLR4 gene knockout (TLR4 <jats:sup>\u2212\/\u2212<\/jats:sup>) neonatal mice were used to test the synergism between the innate immune receptor TLR4 and postbiotics from <jats:italic>Bifidobacteria longum<\/jats:italic> subsp. <jats:italic>infantis<\/jats:italic> (<jats:italic>B. infantis<\/jats:italic>) in development of the premature intestine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>TLR4-mediated postbiotics induced immature enterocyte proliferation and filamentous actin (F-actin) maturation both at the mRNA and protein levels. Proliferation of mRNA levels increased in wild-type mice but not in TLR4 <jats:sup>\u2212\/\u2212<\/jats:sup> mice fed by postbiotics, both in the ileum and colon. Postbiotics can also change tight junction distribution in WT neonatal colon but not in TLR4 <jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data suggest a novel regulation of intestinal development by a synergistic role of the innate immune receptor TLR4 and early life colonizing bacteria, such as <jats:italic>B. infantis<\/jats:italic>. This study should provide new insights into the mechanisms of intestinal maturation as well as opportunities to target novel approaches to NEC prevention and treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Impact<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>The innate immune system and postbiotics affect immature intestinal development.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>The innate immune receptor TLR4 prevention of NEC.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Mechanism of prevention of NEC.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>This is the first time this has been demonstrated in human fetal intestine.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>In vitro process for future clinical studies for prevention of NEC.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41390-024-03676-5","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:12:06Z","timestamp":1739355126000},"page":"268-277","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Synergism between TLR4 and B. infantis in the development of the premature intestine"],"prefix":"10.1038","volume":"98","author":[{"given":"Wuyang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Djebali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ky Young","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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