Investigating the Interactions Between the Gut Microbiome and Inflammation During Pregnancy in a Multiethnic Cohort

Abstract

Preterm birth rates are decreasing across the United States; however, the state of Hawai‘i continues to experience higher risks of adverse pregnancy outcomes. Research is limited within this diverse population and therefore exemplifies a lack of understanding in pathologies related to Indigenous communities. This study aims to investigate dietary influences on the labile maternal microbiome which may contribute to ethnic health disparities. Dietary factors are a significant modulator of microbiota composition and can induce microbial shifts causing changes in metabolite production and cytokine regulation. This interaction subsequently alters systemic immune responses that contribute to many metabolic pathologies which may be implicated in adverse pregnancy outcomes. Forty-one pregnant women were recruited from the four most prominent ethnic groups in Hawai‘i, i.e., Native Hawaiian, Filipino, Japanese, and non-Hispanic White. Rectal microbial swabs were collected during each trimester (12 weeks, 20 weeks, and 34-36 weeks), followed by DNA extraction for 16s RNA sequencing to assess changes in microbiome composition and butyrate production capacity. Blood specimen were collected at two time points (12 weeks and within 24 hours of labor) for inflammatory cytokine profiling using Luminex technology. During the first trimester, inflammatory markers correlated with one another while microbiome characteristics, such as F:B ratio and alpha diversity, were weakly correlated with cytokines. Progression into the third trimester altered correlations of immune response, in that inflammatory markers were no longer strongly associated and there was a shift to slight positive correlations among inflammation states and microbiome characteristics. While there were no ethnic differences observed in cytokine profiles or microbiome characteristics and composition in the first trimester, progression to the third trimester reported differences in physiological responses to pregnancy in an ethnicity dependent manner. Unlike the other ethnic groups, Japanese women did not experience a reduction in F:B ratios over time. Similarly, cytokines IL-6, IL-8 and chemokine MCP-1 and VEGF-A experienced ethnic-specific differences in the third trimester. In the early stages of pregnancy, there was an observed relationship between the gut microbiome and immune responses indicating ethnicity did not impact baseline characteristics. However, the loss of cytokine relationships over the course of pregnancy is likely due to the observed ethnic differences in third trimester immune responses, suggesting ethnicity may be a variable in pregnancy trajectories. Therefore, characterization of ethnic differences in the physiological responses to pregnancy offers novel insight that may help explain the increased prevalence of adverse pregnancy outcomes in Hawai‘i.