Obesity and diet independently affect maternal immunity, maternal gut microbiota and pregnancy outcome in mice

作者：Lieske Wekema, Sam Schoenmakers, Nicole Schenkelaars, Anne Laskewitz, Lei Liu, Lisa Walters, Hermie J. M. Harmsen, Régine P.M. Steegers‐Theunissen, Marijke M. Faas · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1376583 · 被引用次数：15 · 研究领域：Gut microbiota and health、Gestational Diabetes Research and Management、Birth, Development, and Health

Introduction: Maternal obesity poses risks for both mother and offspring during pregnancy, with underlying mechanisms remaining largely unexplored. Obesity is associated with microbial gut dysbiosis and low-grade inflammation, and also the diet has a major impact on these parameters. This study aimed to investigate how maternal obesity and diet contribute to changes in immune responses, exploring potential associations with gut microbiota dysbiosis and adverse pregnancy outcomes in mice. Methods: Before mating, C57BL/6 mice were assigned to either a high-fat-diet (HFD) or low-fat-diet (LFD) to obtain obese (n=17) and lean (n=10) mice. To distinguish between the effects of obesity and diet, 7 obese mice were switched from the HFD to the LFD from day 7 until day 18 of pregnancy ("switch group"), which was the endpoint of the study. T helper (Th) cell subsets were studied in the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP), while monocyte subsets and activation status were determined in maternal blood (flow cytometry). Feces were collected before and during pregnancy (day 7,14,18) for microbiota analysis (16S rRNA sequencing). Pregnancy outcome included determination of fetal and placental weight. Results: Obesity increased splenic Th1 and regulatory T cells, MLN Th1 and PP Th17 cells and enhanced IFN-γ and IL-17A production by splenic Th cells upon ex vivo stimulation. Switching diet decreased splenic and PP Th2 cells and classical monocytes, increased intermed...