Diet and Pre-Intervention Washout Modifies the Effects of Probiotics on Gestational Diabetes Mellitus: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Dynamic interactions among gestational diabetes mellitus (GDM), gut microbiota, inflammation, oxidative stress, and probiotics are increasingly acknowledged. This meta-analysis aimed to summarize the effects of probiotics in GDM, focusing on lifestyle intervention and pre-intervention washout, in addition to metabolic, inflammation, oxidative stress, and pregnancy outcomes. Three electronic databases (i.e., PubMed, Scopus, and CENTRAL) were searched from inception until October 2020. A meta-analysis was performed, and the effect sizes were reported as either mean differences or odds ratios with 95% confidence intervals. Altogether, 10 randomized controlled trials enrolling 594 participants were included. The meta-analysis indicated that probiotics supplementation effectively reduced fasting plasma glucose by 3.10 mg/dL, and subgroup analyses suggested that the duration of intervention, number of species, pre-intervention washout period, and dietary intervention may determine the effects of probiotics. Probiotics also reduced the level of inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and malondialdehyde), incidence of macrosomia, and newborn hospitalization. In conclusion, this meta-analysis suggests that probiotics may have positive effects on metabolic, inflammation, oxidative stress, and neonatal outcomes in women with GDM. Additionally, diet and pre-intervention washout may modify the effects of probiotics. Future studies are warranted on a larger scale to ascertain the clinical significance.

Updates on Gestational Diabetes

“…These factors upregulate the expression of proinflammatory markers and suppress the expression of anti-inflammatory markers. 2 Sutterella is positively correlated with C-reactive protein levels. Furthermore, gut microbiota dysbiosis is linked to overproduction of oxidative stress species (ROS), elevated lipid peroxidation and oxidative stress markers, in addition to reduced antioxidant markers.…”

“…However, the effectiveness of lifestyle intervention in managing GDM can be challenging, as only 16-55% of pregnant women adhere. 2 Studies have consistently reported that overall obesity predicts GDM. However, other obesity phenotypes such as central obesity and adiposity may have differential associations, as the risk factors for GDM are less well known.…”

“…Inflammation, oxidative stress reactions and metabolic pathways are associated with insulin resistance, and may explain abnormal lipid and glucose metabolism in pregnant women. 2 Probiotics are defined as "live microorganisms which, when properly administered, confer a health benefit on the host". Certainly, probiotic effects can be influenced by a number of factors, including lifestyle and dietary intake.…”

“…The prevalence of GDM in 173 countries ranges from <1% to 28% depending on country and diagnostic criteria. 2 . It is estimated that more than 5% of all pregnancies in Europe are complicated by GDM.…”

“…Women with GDM are at increased risk of cardiovascular events, and their children are predisposed to the future risk of obesity and T2DM. 2,4,5 Evan et al 3 recently concluded, in qualitative research, that there are perceptions around GDM that, if not addressed, are likely to compromise the effect of lifestyle interventions. For example, although many women know that there is an association between GDM and T2D in their future, they may not understand this risk as GDM has minimal and transient impact on their lives.…”