Microbiota-targeted interventions and clinical implications for maternal-offspring health: An umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Abstract

Background Microbes in the human body are the determinants of life-long health and disease. Microbiome acquisition starts in utero and matures during early childhood through breastfeeding. However, maternal gut dysbiosis affects the maternal-offspring microbiome interplay. Lines of evidence on dysbiosis-targeted interventions and their effect on maternal-offspring health and gut microbiome are inconsistent and inconclusive. Therefore, this study summarised studies to identify the most common microbiota-targeted intervention during pregnancy and lactation and to comprehensively evaluate its effects on maternal and offspring health. Methods This umbrella review was conducted by systematically searching databases such as PubMed and the Web of Science from inception to 2 September 2023. The quality was assessed using the Assessment of Multiple Systematic Reviews-2 checklist. The Grading of Recommendations Assessment, Development, and Evaluation was used for grading the strength and certainty of the studies. The overlap of primary studies was quantified by the corrected covered area score. Results A total of 17 systematic reviews and meta-analyses with 219 randomised controlled trials, 39 113 mothers, and 20 915 infants were included in this study. About 88% of studies had moderate and above certainty of evidence. Probiotics were the most common and effective interventions at reducing gestational diabetes risk (fasting blood glucose with the mean difference (MD) = -2.92, -0.05; I2 = 45, 98.97), fasting serum insulin (MD = -2.3, -2.06; I2 = 45, 77), glycated haemoglobin (Hb A1c) = -0.16; I2 = 0.00)), Homeostatic Model Assessment of insulin resistance (HOMA-IR) (MD = -20.55, -0.16; I2 = 0.00, 72.00), and lipid metabolism (MD = -5.47, 0.98; I2 = 0.00, 90.65). It was also effective in preventing and treating mastitis (risk ratio (RR) = 0.49; I2 = 2.00), relieving anxiety symptoms (MD = -0.99, 0.01; I2 = 0.00, 70.00), depression in lactation (MD = -0.46, -0.22; I2 = 0.00, 74.00) and reducing recto-vaginal bacterial colonisation (odds ratio (OR) = 0.62; I2 = 4.80), and with no adverse events. It also effectively remodelled the infant gut microbiome (MD = 0.89; I2 = 95.01) and prevented infant allergies. However, studies on pregnancy outcomes and preeclampsia incidences are limited. Conclusions Our findings from high-quality studies identify that probiotics are the most common microbiome interventions during pregnancy and lactation. Probiotics have a strong impact on maternal and offspring health through maintaining gut microbiome homeostasis. However, further studies are needed on the effect of microbiota-targeted interventions on maternal cardiometabolic health, pregnancy, and neonatal outcomes. Registration This umbrella review was registered with PROSPERO, CRD42023437098.