{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T18:21:28Z","timestamp":1768760488514,"version":"3.49.0"},"reference-count":83,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5P20GM134973"],"award-info":[{"award-number":["5P20GM134973"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 days in mouse pups leads to increased villus length and crypt depth, and increased goblet and Paneth cells, compared to controls. We also show that HA 35 KDa leads to an increased predominance of Clostridiales Ruminococcaceae, Lactobacillales Lactobacillaceae, and Clostridiales Lachnospiraceae. In seeking the mechanisms involved in the changes, bulk RNA seq was performed on samples from the terminal ileum and identified upregulation in several genes essential for cellular growth, proliferation, and survival. Taken together, this study shows that HA 35 KDa supplemented to mouse pups promotes intestinal epithelial cell proliferation, as well as the development of Paneth cells and goblet cell subsets. HA 35 KDa also impacted the intestinal microbiota; the implications of these responses need to be determined.<\/jats:p>","DOI":"10.3390\/nu13062030","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:25:46Z","timestamp":1623709546000},"page":"2030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Acceleration of Small Intestine Development and Remodeling of the Microbiome Following Hyaluronan 35 kDa Treatment in Neonatal Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-564X","authenticated-orcid":false,"given":"Hala","family":"Chaaban","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-5383","authenticated-orcid":false,"given":"Kathryn","family":"Burge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-8198","authenticated-orcid":false,"given":"Jeffrey","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MaJoi","family":"Trammell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi S.","family":"Keshari","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-6160","authenticated-orcid":false,"given":"Robert","family":"Silasi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girija","family":"Regmi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-0893","authenticated-orcid":false,"given":"Cristina","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0264-5721","authenticated-orcid":false,"given":"Misty","family":"Good","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-723X","authenticated-orcid":false,"given":"Steven J.","family":"McElroy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-9278","authenticated-orcid":false,"given":"Florea","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1651-2227.1994.tb13236.x","article-title":"Necrotizing enterocolitis\u2014Multisystem organ failure of the newborn?","volume":"396","author":"Morecroft","year":"1994","journal-title":"Acta Paediatr. 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