Pregnancy Alters Gut Microbiome and Impacts Immune Response

Pregnancy leads to an eruption of physiological and metabolic changes in the body. Among many of these changes are dramatic fluctuations in the immune system, but how these changes may take place has alluded scientists until now.

In a new study, published in mSystem, researchers uncovered how the gut microbiome plays a role in driving these pregnancy-induced alterations in the immune system.

Gut microbiome and pregnancy

Changes in the gut microbiome are known to influence human health. Studies have found several associations with gut microbiota dysbiosis and many human diseases including cancer, inflammatory bowel disease and mental health conditions such as depression and anxiety. Many of these conditions have been linked to the metabolites that are produced by microorganisms.

Similar to almost every organ in the body, the gut microbiome also undergoes a dramatic shift during pregnancy, favoring species that are linked to the digestion of breastmilk such as Bifidobacterium. Disruptions in this shift of microbiome composition have been linked to pregnancy conditions including preeclampsia – a life-threatening condition characterized by high blood pressure 20 weeks post-gestation.

Although previous research has suggested that the typical pregnancy-induced changes may influence physiological processes in the mother through metabolites, how they impact maternal immunity is still unclear.

“To the best of our knowledge, these associations were first explored in our study,” said first author Dr. Ting Huang from the First Affiliated Hospital of Jinan University.

How do metabolites influence immunity?

Huang and team used fecal and blood samples from 30 healthy pregnant women and 15 non-pregnant women to analyze their gut microbiota, metabolite profiles and immune system status. Samples were collected during or after the 37th week of pregnancy from the pregnant cohort and on the 14th day of the menstrual cycle from the non-pregnant cohort.

Across both groups, Firmicutes was the most dominant phylum, however, pregnant participants showed a higher relative abundance of both Actinobacteriota and Proteobacteria. Bacteroidota bacteria also accounted for a smaller relative share of the microbial population in pregnant women compared to those in non-pregnant women.

The researchers also noted a distinct difference in cytokine profiles between both groups.

The pregnant cohort displayed an increase in cytokines that act against inflammation; and a decrease in those that promote inflammation, compared to the non-pregnant group.

Huang and team also identified specific metabolites associated with each separate cohort, suggesting a pregnancy-induced metabolite profile, or metabolome. Many of the metabolites were connected to bile acid secretion, which has been tied to inflammation. The pregnant cohort also displayed a decrease in pro-inflammatory cytokines, suggesting the immune system may be suppressed in pregnancy.

Gut microbes interact with host metabolites

The researchers identified 46 connections between the microbes, metabolites and cytokines. The study suggests the microbes enriched in pregnant women may inhibit the immune system by inhibiting pro-inflammatory metabolites.

“The results support the idea that gut microbes interact with host metabolites to change cytokine levels in the blood,” said Huang.

Similar to many gut microbiome studies, the results do not establish causation. Further investigation is required in a larger sample size to adjust for individual differences and cofounding factors, such as diet.

Reference: Huang T, Liang X, Bao H, et al. Multi-omics analysis reveals the associations between altered gut microbiota, metabolites, and cytokines during pregnancy. mSystems. 2024. doi: 10.1128/msystems.01252-23

This article is a rework of a press release issued by The American Society for Microbiology. Material has been edited for length and content.