Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response

Simple item page
dc.contributor.authorRosa, Fernandaen
dc.contributor.authorSharma, Ashok K.en
dc.contributor.authorGurung, Manojen
dc.contributor.authorCasero, Daviden
dc.contributor.authorMatazel, Katelinen
dc.contributor.authorBode, Larsen
dc.contributor.authorSimecka, Christyen
dc.contributor.authorElolimy, Ahmed A.en
dc.contributor.authorTripp, Patriciaen
dc.contributor.authorRandolph, Christopheren
dc.contributor.authorHand, Timothy W.en
dc.contributor.authorWilliams, Keith D.en
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorYeruva, Laxmien
dc.date.accessioned2022-11-10T15:05:59Zen
dc.date.available2022-11-10T15:05:59Zen
dc.date.issued2022-06-29en
dc.description.abstractHuman milk harbors complex carbohydrates, including human milk oligosaccharides (HMOs), the third most abundant component after lactose and lipids. HMOs have been shown to impact intestinal microbiota, modulate the intestinal immune response, and prevent pathogenic bacterial binding by serving as decoy receptors. However, the direct effect of HMOs on intestinal function and immunity remains to be elucidated. To address this knowledge gap, 21-day-old germ-free mice (C57BI/6) were orally gavaged with 15 mg/day of pooled HMOs for 7 or 14 days and euthanized at day 28 or 35. A set of mice was maintained until day 50 to determine the persistent effects of HMOs. Control groups were maintained in the isolators for 28, 35, or 50 days of age. At the respective endpoints, intestinal tissues were subjected to histomorphometric and transcriptomic analyses, while the spleen and mesenteric lymph nodes (MLNs) were subjected to flow cytometric analysis. The small intestine (SI) crypt was reduced after HMO treatment relative to control at days 28 and 35, while the SI villus height and large intestine (LI) gland depth were decreased in the HMO-treated mice relative to the control at day 35. We report significant HMO-induced and location-specific gene expression changes in host intestinal tissues. HMO treatment significantly upregulated genes involved in extracellular matrix, protein ubiquitination, nuclear transport, and mononuclear cell differentiation. CD4+ T cells were increased in both MLNs and the spleen, while CD8+ T cells were increased in the spleen at day 50 in the HMO group in comparison to controls. In MLNs, plasma cells were increased in HMO group at days 28 and 35, while in the spleen, only at day 28 relative to controls. Macrophages/monocytes and neutrophils were lower in the spleen of the HMO group at days 28, 35, and 50, while in MLNs, only neutrophils were lower at day 50 in the 14-day HMO group. In addition, diphtheria toxoid and tetanus toxoid antibody-secreting cells were higher in HMO-supplemented group compared to controls. Our data suggest that HMOs have a direct effect on gastrointestinal tract metabolism and the immune system even in the absence of host microbiota.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fimmu.2022.907529en
dc.identifier.issn1664-3224en
dc.identifier.other907529en
dc.identifier.pmid35844612en
dc.identifier.urihttp://hdl.handle.net/10919/112554en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjecthuman milk oligosaccharidesen
dc.subjectHMOen
dc.subjectimmunityen
dc.subjectgastrointestinal tracten
dc.subjectneonatalen
dc.titleHuman Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Responseen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fimmu-13-907529.pdf
Size:
11.12 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Scholarly Works, Biomedical Sciences and Pathobiology