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Research Project: Impact of Maternal Influence and Early Dietary Factors on Child Growth, Development, and Metabolic Health

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Title: Maternal immune cell gene expression during gestation associates with infant gut microbiota composition

Author
item Gurung, Manoj
item MULAKALA, BHARATH - Texas A&M Agrilife
item SCHLEGEL, BRENT - University Of Pittsburgh
item RAJASUNDARAM, DHIVYAA - University Of Pittsburgh
item ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS)
item Yeruva, Laxmi

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/13/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Objectives: To investigate the associations between peripheral blood mononuclear cell (PBMC) gene expression and maternal overweight and obesity status as well as infant gut microbiota. Methods: Women with normal weight (NW, BMI 18.5-24.9 kg/m2) or overweight (OW, BMI 25-29.9 kg/m2) with blood samples at 12 (n=9, NW, n=9, OW), 24 (n=10, NW, n=9, OW), and 36 (n = 10, NW, n = 9, OW) weeks of gestation and matching infant microbiome at 1 month postpartum (previously published) were included in this analysis. PBMC gene expression was determined using bulk mRNA sequencing and differentially expressed genes were analyzed using DESeq2 followed by pathway analysis using DAVID. Integrative multi-omics and pairwise cross-omics analyses, with sparse partial least square regression-based modeling was used for association analyses. Results: At 12 weeks of gestation, genes and pathways related to inflammation and immune response were upregulated in OW subjects, though no such changes were observed at 24 and 36-week gestation. Infant microbial genera Sutterella was positively associated with the expression of 33 genes in PBMC (e.g. CYP2E1, SLC29A2, SFXN2) (r>0.7) at 12 weeks gestation. The 13 other genera (eg. Akkermansia) were positively associated with the expression of 25 genes in PBMC (eg. CPS1). Among these genes, the expression of 17 genes was negatively associated to Bifidobacterium. At 24 weeks of gestation, Enterobacter and Serratia abundance were positively correlated to the expression of several genes in PBMC, including IFI27 and CD5L. Functional annotation of genes associated with Enterobacter revealed enrichment of the immunity pathway. Phylum Proteobacteria was negatively correlated to 44 genes in PBMC including CD177, CD79A, ADAM29, and IL1RL2. Functional analysis of these genes identified immunity and adaptive immunity pathways as the significantly enriched pathways. At 36W of gestation, Akkermansia was positively associated with the expression of 16 genes in PBMC (e.g. RAB7B). Conclusions: Genes and pathways related to inflammation and immune responses were upregulated in OW subjects at 12 weeks of gestation. Maternal immunity related pathways were associated with infant gut microbiota, suggesting a potential role of maternal immune response in infant gut microbiota composition. Funding: USDA-ARS.