Probiotics and Fibre Prevention and Treatment of Gestational Diabetes

Gestational diabetes (GDM) is a diagnosis that describes glucose intolerance with the onset of diabetes during pregnancy in a previously nondiabetic woman.^[1] With a prevalence of 8–18% in Canadian pregnancies,^[2] screening is recommended after approximately 24 weeks gestation.^[3] It is also recognized that GDM occurs more often in overweight and obese women, and is associated with an increased risk of multiple complications in both mother and baby including preeclampsia, and the necessity for a caesarian-section birth due to higher than normal-for-gestation birth weight.^[3] Additionally concerning is that mothers with GDM have a 20–50% risk of developing classical type 2 diabetes mellitus (T2DM) postpregnancy.^[4]

For the infant, having a mother diagnosed with GDM increases the risk of higher than normal adiposity, shoulder dystocia, and neonatal hypoglycemia.^[3] It has been postulated that a chronic low-grade inflammation may be a cofactor in obesity.^[5] This coincides with the idea that maternal insulin resistance can lead to inflammation.^[6] Although pharmaceutical preparations for glucose control exist, prevent is key as short-term interventions may not reduce long-term complications in mother or infant.^[3] When treating or preventing T2DM, combining diet and exercise has been known to significantly improve blood glucose regulation and insulin sensitivity in nonpregnant individuals.^[7] However, for pregnant women, there are mixed results with these lifestyle and diet interventions, as compliance and consistency is typically more difficult.^[3] Many studies have looked at the role of the gut microbiome in inflammation, T2DM, insulin resistance, and weight gain.^[8] Multiple factors influence gut microflora including antibiotic use (at any time from infancy onward) and current diet,^[3] with fibre intake being increasingly beneficial.^[7] Diet-based interventions have shown the greatest reduction in gestational weight gain, lowering serum leptin levels by 20%.^[7] This can significantly affect glucose control and insulin sensitivity, as well as potentially modify the low-grade inflammation we see in overweight and obese patients. Additionally, researchers have been investigating the role of probiotics as mediators of inflammation,^[8] and how this fits into the prevention and treatment of GDM.

Probiotic Treatment for GDM

Probiotics work by altering the gut microbiome and modifying the concentration of plasma lipopolysaccharides.^[7] Their presence in the gut, and the metabolites formed by these probiotic bacteria, induces modifications in inflammatory pathways and affects insulin sensitivity.^[7] In a 2016 study, Karamali suggested that certain strains of probiotics may act by blocking the suppression of glucose transporter type 4 (GLUT4), and it may be by this mechanism that we are able to influence glucose control.^[8] One study by Luoto et al (2010) showed that probiotic supplementation in normal-weight women during pregnancy was able to reduce the rate of GDM from 34% to 13%.^[9] Of interest are the specific strains used in this study. Differing probiotic strains can have different effects in the body, affecting distinctive pathways and showing improvements in multiple areas of health. For example, we know that certain species and strains are more beneficial for gas and colic, meanwhile others are better at preventing diarrhea from antibiotic use. Similarly, not every supplemental probiotic strain will benefit insulin sensitivity, appetite, and glucose control. Current research in this area shows just that. Two studies by Lindsay et al (2014 and 2015) treated obese pregnant women, and those newly diagnosed with GDM, with the strain Lactobacillus salivarius UCC118 at a dose of 1 billion colony-forming units (CFU).^[10][11] In both cases, no beneficial effect was reported in glycemic control, or other pregnancy outcomes. However, one outcome was a reduction in total and LDL cholesterol, demonstrating benefit to lipid levels, but not in reducing GDM status.^[11] Karamali et al (2016) used 2 billion CFU of each Lactobacillus acidophilus and Bifidobacterium bifidum in women who had been diagnosed with GDM, and found benefit with this intervention within six weeks of treatment.^[8] Improvements were seen in glycemic control, triglyceride levels, and VLDL concentrations. Additionally, there were significant reductions in fasting blood glucose and serum insulin concentrations when compared with placebo.^[8] A 2015 study used a combination of four strains with 4 billion CFU per strain: L. acidophilus LA-5, Bifidobacterium animalis lactis BB‑12, Streptococcus thermophilus STY‑31, and Lactobacillus delbrueckii bulgaricus LBY‑27.^[6] After eight weeks of intervention, women with a diagnosis of GDM presented with lower gestational weight gain after probiotic treatment compared to placebo. The change was significant after six weeks of intervention, and by the end of the study, the probiotic group had significantly lower fasting blood glucose levels, and a decrease in insulin resistance of almost 7%.^[6] One trend that seems to appear in research is the use and subsequent benefit of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 in GDM. The study by Luoto (2010) used a dosage of 10 billion CFU for each of these strains, but other combinations and dosages are also being investigated.^[9] The SPRING study by Nitert et al (2013) in Australia has been set up to test the same two strains as in Luoto’s 2010 study, but at a dose of 1 billion CFU for 24 weeks during pregnancy, starting at 16 weeks of gestation.^[3] This study, once completed and published, will shed light on whether these strains may be used in the prevention of GDM in high-risk pregnancies among overweight and obese women. That said, a Cochrane review published in 2014, without this data, concluded that when started in early pregnancy, probiotic intervention reduced the rate of GDM as well as infant birth weight. However, to date, there have been no reported differences in the rate of miscarriage, stillbirth, or neonatal death.^[12] Throughout several studies of probiotics in pregnancy, one thing that appears clear is the safety profile of probiotic intervention of these tested strains. No significant adverse effects have been reported to date on mother or offspring for probiotics, even with first exposure during the first trimester.^[7]

Dietary Interventions and Fibre Intake

A meta-analysis of interventions for GDM showed dietary interventions were able to reduce rates of GDM by 33%, but when probiotics were added with these dietary changes/guidelines, the risk was reduced by 60%.^[7] As well, dietary interventions were able to reduce the risk of gestational hypertension and pre-eclampsia by 84% and 34%, respectively.^[7]

Dietary interventions prepregnancy and continuing during gestation have the potential for preventing GDM due to the ability to control glycemic load and gestational weight gain.^[7] By adding 10 g of fibre daily, the risk of GDM is reduced by 25%.^[7] The role of both fibre and beneficial probiotic species go hand-in-hand. The research shows a benefit for both interventions on reducing the risk of GDM and improving insulin sensitivity, but also, a high-fibre diet also contributes to the maintenance of a healthy gut microbiome, as beneficial bacteria use fibre as a fuel source. This promotes their survival and proliferation in the lower gastrointestinal tract. Dietary fibre has many other benefits including delaying gastric emptying and slowing glucose absorption, resulting in smaller increases in insulin levels.^[2] We know that high-glycemic-load diets combined with low fibre intake increases the risk of GDM.^[2] However, with any intervention or treatment, it’s important to keep the big picture in mind. Fibre intake, and possibly probiotic supplementation, both seem to benefit glucose control in overweight and obese women, but all aspects of diet and lifestyle need to be evaluated. Restricting carbohydrates and simple sugars to some degree will also be helpful, but this needs to be properly calculated and monitored by a health-care practitioner. Recommendations for glucose control in pregnancy restrict carbohydrates to 35–40% of daily calories,^[1] though this calculation may vary slightly depending on individual cases. For example, multiple studies have shown the benefit of mild to moderate physical activity preconception and during pregnancy. One study of daily stair-climbing showed a decreased risk of GDM by 49–78% when compared to non–stair-climbers.^[2] From a safety aspect, no adverse effects have been reported on the health of the mother or fetus in pregnant women who participate in mild to moderate physical activity during pregnancy.^[2]

Conclusions

Although diet and lifestyle modifications have the ability to modify glucose control and prevent GDM, major changes in dietary habits may be difficult for pregnant women to follow consistently. Of important note during the first trimester would be to emphasize a fibre-rich diet, while restricting simple carbohydrates. Probiotic supplementation may serve as an additional or alternative treatment while continuing counselling on diet and physical activity. To date, several probiotic strains and combinations have shown benefit in modifying glucose regulation. Among them are species such as Lactobacillus rhamnosus, Bifidobacterium animalis lactis, Bifidobacterium bifidum, and Lactobacillus acidophilus, though others are still being researched.