Dataset Information

Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection.

ABSTRACT: Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.

SUBMITTER: Ramani S

PROVIDER: S-EPMC6258677 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection.

Ramani Sasirekha S Stewart Christopher J CJ Laucirica Daniel R DR Ajami Nadim J NJ Robertson Bianca B Autran Chloe A CA Shinge Dhairyasheel D Rani Sandya S Anandan Sasirekha S Hu Liya L Ferreon Josephine C JC Kuruvilla Kurien A KA Petrosino Joseph F JF Venkataram Prasad B V BV Bode Lars L Kang Gagandeep G Estes Mary K MK

Nature communications 20181127 1

Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neona ...[more]

PMID: 30479342

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Project description:BackgroundInfant gut microbiota composition is influenced by various factors early in life. Here, we investigate associations between infant gut microbiome development, infant age, breastfeeding duration, and human milk oligosaccharides (HMO) composition in breastmilk.MethodsA total of 94 mother-infant pairs were recruited as part of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) (Cambridge, UK). Infant stool samples (n = 337) were collected at 2 week, 6 week, 3 month, and 6 month of age. The 16S rRNA V3-V4 rRNA region was sequenced using MiSeq Illumina to determine microbiota composition and diversity. Mother's hindmilk samples were collected at birth, 2 week, 6 week, 3 month, and 6 month postpartum. Concentrations of five neutral [2'FL, 3'FL, lacto-N-fucopentaose 1 (LNFP1), LNnT, LNT] and two acidic (3'SL, and 6'SL) HMOs were measured in all milk samples using High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD). We explored the associations between infant gut microbiome parameters and age, duration of exclusive breastfeeding (EBF), and levels of individual HMOs.ResultsBifidobacterium was the most abundant genus in infant stool at all-time points, irrespective of breastfeeding duration, with an overall mean relative abundance of 70%. The relative abundance of B. bifidum in stool from infants who were breastfed for longer than 6 months was significantly higher compared to the infant breastfed up to 3 months (p = 0.0285). Alpha-diversity (both Shannon and ASV-level Richness) of infant gut microbiota showed a biphasic change with infant age, decreasing from 2 weeks until 3 months and then increasing until 6 months of age. Bifidobacterium relative abundance was associated with higher concentrations of 2'FL and LNFP1 in breastmilk across all time-points (p = 0.049 and 0.017, respectively), with trends toward a higher abundance of B. longum species. No significant association with Bifidobacterium was found for breastmilk LNnT, 3'SL, and 6'SL levels.ConclusionOur study is in line with previous data demonstrating that EBF duration in the first months of life impacts infant gut microbiota composition. The observed links between specific HMOs in breastmilk and bacteria in infant stool provide evidence of how mother's milk affects infant microbiome development.

Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Dataset Information

Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection.

Publications

Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection.

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