Interrelations between microbiota, metabolism and low-grade inflammation with obesity and gestational diabetes mellitus: means to intervene during pregnancy

Dissertation

Abstract

Pregnant women with overweight and obesity may exhibit altered circulating low- grade inflammatory and metabolic profile and gut and vaginal microbiota which may contribute to the development of gestational diabetes mellitus (GDM). These are further exaggerated in obesity. In this thesis, the aim was to investigate the interaction of low-grade inflammation, metabolism and gut and vaginal microbiota in pregnant women with obesity and overweight and whether these are related to the onset of GDM. Further, the effect of dietary intervention with fish oil and/or probiotics on these factors were studied.

The study involved pregnant women with overweight and obesity (n = 99–434) in early and late pregnancy. Blood, faecal and vaginal samples were analysed for low-grade inflammatory and metabolic markers (metabolites, phosphorylated insulin-like growth factor binding-protein 1 (phIGFBP-1), IGFBP-1, active matrix metalloproteinase 8 (aMMP-8) and fatty acids) and gut and vaginal microbiota and vaginal aMMP-8, respectively. The women were randomised into four intervention groups (fish oil+placebo, probiotics+placebo, fish oil+probiotics, placebo+placebo) from early pregnancy onwards. The fish oil capsules contained 2.4 g of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs): 1.9 g docosahexaenoic acid, 0.22
g eicopentaenoic acid, and the remaining amount other n-3 fatty acids and probiotics Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, each with 1010 colony-forming units per capsule.

In early pregnancy, the pregnant women with obesity had higher level of low- grade inflammatory markers and distinct metabolic profile and gut microbiota as compared to the women with overweight. Low serum phIGFBP-1, IGFBP-1 and high serum n-3 LC-PUFAs in early pregnancy were related to the onset of GDM. Some vaginal bacterial genera and species were related to GDM. The fish oil and/or probiotics intervention did not influence low-grade inflammation, serum phIGFBP-1, IGFBP-1 or serum/vaginal aMMP-8 but it reduced the relative abundance of some bacterial genera and species, namely fish oil reduced Ureaplasma urealyticum, probiotics Ureaplasma, U. urealyticum and Prevotella disiens, fish oil+probiotics Dialister invisus and P. timonensis, in vagina and increased serum n-3 LC-PUFAs.

In conclusion, obesity alters inflammatory and metabolic profile and gut microbiota in pregnant women. Serum phIGFBP-1, IGFBP-1 and serum n-3 LC- PUFAs as well as vaginal microbiota in early pregnancy were related to the onset of GDM. The fish oil and/or probiotics resulted lower relative abundance of potential pathobionts in vagina.

Author

Noora Houttu PhD, Postdoctoral Researcher,
University of Turku, Institute of Biomedicine,
Medical microbiology and immunology
Nutrition and Food Research Center