Maternal immune cell gene expression associates with maternal gut microbiome, milk composition and infant gut microbiome

Authors: Gurung, Manoj; MULAKALA, BHARAT - Texas A&M Agrilife; SCHLEGEL, BRENT - University Of Pittsburgh; RAJASUNDARAM, DHIVYAA - University Of Pittsburgh; SHANKAR, KARTIK - University Of Colorado; BODE, LARS - University Of California, San Diego; Ruebel, Meghan; SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC); MARTINEZ, AUDREY - Arkansas Children'S Nutrition Research Center (ACNC); ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS); Yeruva, Laxmi

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/26/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Overweight status in the U.S. is increasing steadily, particularly in women of childbearing age. Further, overweight status is not only a risk for mothers during pregnancy but also predisposes babies to obesity, cardiovascular diseases, type 2 diabetes, impaired cognition, and allergies. Inflammation has been observed in adults with overweight or obese condition. However, little information is available on the impact of overweight during pregnancy on immune cell gene expression. Moreover, limited information is available on the association of immune cell response and its association to maternal milk components, gut microbiota, and dietary components, as well as with the infant's fecal microbiota. The result of this study showed how being overweight during pregnancy influences the expression levels of immune cell genes in each trimester. In addition, it also provided a snapshot of complex interconnections between maternal gene expression, gut microbiota, dietary components, milk components, and infant fecal microbiota. Further understanding of this association may aid in developing powerful strategies against obesity-mediated effects.

Technical Abstract: 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.