Association between gut microbiota and metabolic health status in pregnant women with obesity

Abstract

Background and objective. Obesity is known to predispose to cardiometabolic diseases, but not all individuals with obesity are equally at risk based on their metabolic health status. While individuals with metabolically unhealthy obesity (MUO) are characterized by metabolic dysfunction, those with meta- bolically healthy obesity (MHO) seem protected from the increased cardiometabolic disease risk. Alt- hough the gut microbiota has been associated with obesity and metabolic health, its association to the metabolic phenotypes of obesity remains to be elucidated. This is especially crucial in pregnancy, as the influence of maternal metabolic health has implications that reach both the mother and offspring. Con- sequently, the aims in this thesis are to define criteria for MHO and MUO in pregnant women and to investigate whether gut microbiota diversity, composition, and function differ in pregnant women with MHO and pregnant women with MUO. Methods. Data from a mother-child study with 439 women recruited in early pregnancy (gestational weeks, 13.9 ± 2.1) was used. Previous literature was reviewed to define criteria for MHO and MUO. Early pregnancy gut microbiota was analyzed in women with MHO and women with MUO at species and at genus level using metagenomic sequencing data. Gut microbiota alpha diversity, beta diversity, and differential abundance of microbial taxa and predicted metabolic pathways were compared between groups. Results. Based on reviewed literature, MHO was defined in the absence and MUO in the presence of ≥2 of the following metabolic aberrations: high blood pressure, high fasting plasma glucose, high tri- glycerides, and low HDL-cholesterol. This resulted in 79 pregnant women being allocated into a group with MHO and 29 into a group with MUO. Gut microbiota alpha and beta diversity did not differ be- tween groups. Although no differences in composition were observed at genus level, the species Clos- tridium sp AT4 was found to be more abundant in women with MUO. Moreover, multiple microbial metabolic pathways differed in abundance between groups. Pathways related to BCAA, coenzyme A, and thiamine phosphate biosynthesis and to carbohydrate catabolism were more abundant in women with MHO, whereas those related to amino acid, nucleotide, fatty acid, and quinol biosynthesis and to the TCA cycle were more abundant in women with MUO. Conclusions. One microbial species and multiple microbial metabolic pathways differ in abundance between women with MHO and women with MUO in early pregnancy. To elucidate whether these differences might contribute to the host’s metabolic health status, further studies using a multi-omics approach are called for.