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dc.contributor.authorMa, Bing
dc.contributor.authorSundararajan, Sripriya
dc.contributor.authorNadimpalli, Gita
dc.contributor.authorFrance, Michael
dc.contributor.authorMcComb, Elias
dc.contributor.authorRutt, Lindsay
dc.contributor.authorLemme-Dumit, Jose M
dc.contributor.authorJanofsky, Elise
dc.contributor.authorRoskes, Lisa S
dc.contributor.authorGajer, Pawel
dc.contributor.authorFu, Li
dc.contributor.authorYang, Hongqiu
dc.contributor.authorHumphrys, Mike
dc.contributor.authorTallon, Luke J
dc.contributor.authorSadzewicz, Lisa
dc.contributor.authorPasetti, Marcela F
dc.contributor.authorRavel, Jacques
dc.contributor.authorViscardi, Rose M
dc.date.accessioned2022-06-16T13:39:07Z
dc.date.available2022-06-16T13:39:07Z
dc.date.issued2022-06-13
dc.identifier.urihttp://hdl.handle.net/10713/19187
dc.description.abstract"Leaky gut," or high intestinal barrier permeability, is common in preterm newborns. The role of the microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7 and 326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found that a significantly increased abundance of Bifidobacterium breve and a diet rich in mother's breastmilk were associated with intestinal barrier maturation during the first week of life. We combined these factors using genome-resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposes mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical toward advancing therapeutics to prevent and treat hyperpermeable gut-associated conditions, including necrotizing enterocolitis (NEC). IMPORTANCE Despite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. "Leaky gut," or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in "at-risk" preterm neonates are critical for decreasing the risk of potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function remain largely uncharacterized. In this study, we reveal the critical role of a sufficient breastmilk feeding volume and the specialized carbohydrate metabolism capability of Bifidobacterium in the coordinated postnatal improvement of the intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation and prevent NEC and other adverse health conditions in preterm infants.en_US
dc.description.urihttps://doi.org/10.1128/mbio.01299-22en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofmBioen_US
dc.subjectBifidobacteriumen_US
dc.subjectgut microbiomeen_US
dc.subjecthuman milk oligosaccharidesen_US
dc.subjectintestinal barrier maturationen_US
dc.subjectleaky guten_US
dc.subjectpreterm infanten_US
dc.titleHighly Specialized Carbohydrate Metabolism Capability in Strains Associated with Intestinal Barrier Maturation in Early Preterm Infants.en_US
dc.typeArticleen_US
dc.identifier.doi10.1128/mbio.01299-22
dc.identifier.pmid35695455
dc.source.journaltitlemBio
dc.source.beginpagee0129922
dc.source.endpage
dc.source.countryUnited States


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