October 4, 2017

Probiotic Supplementation in Gestational Diabetes

Can it improve maternal and infant outcomes?
A randomized trial pits probiotics against placebo in pregnant women with gestational diabetes. Will probiotics improve outcomes in this vulnerable population?


Karamali M, Nasiri N, Shavazi NT, et al. The effects of synbiotic supplementation on pregnancy outcomes in gestational diabetes. Probiotics Antimicrob Proteins (published online ahead of print August 7, 2017). doi: 10.1007/s12602-017-9313-7


Randomized, double-blind, placebo-controlled clinical trial


Sixty pregnant women in Iran aged 18 to 40 years with gestational diabetes who were not on oral hypoglycemic agents; exclusion criteria included preeclampsia, eclampsia, thyroid disorders, tobacco use (smoking), kidney or liver disease, and current probiotic use (including yogurt and kefir)


Participants were randomly assigned to consume 1 probiotic capsule or placebo each day for 6 weeks. The probiotic capsule contained the following ingredients:

  • Lactobacillus acidophilus strain T16 (IBRC-M10785), 2 x 109 CFU/g
  • Lactobacillus casei strain T2 (IBRC-M10783), 2 x 109 CFU/g
  • Bifidobacterium bifidum strain T1 (IBRC-M10771), 2 x 109 CFU/g
  • Inulin, 800 mg

All women in the study also consumed 400 ug folic acid per day starting at the beginning of pregnancy and 60 mg ferrous sulfate per day starting in their second trimester. Compliance and diet were monitored.

Study Parameters Assessed

All women and newborns were weighed and measured (weight, length, and head circumference for infants; height and weight for mothers) at baseline and end of trial. Fasting blood samples were obtained at baseline and end of treatment to determine serum levels of inflammatory markers and markers for oxidative stress. Newborns were assessed for hyperbilirubinemia (defined as total serum bilirubin ≥15 mg/dL for infants aged 25-48 hours, ≥18 mg/dL for infants aged 49-72 hours, and ≥20 mg/dL for infants older than 72 hours). Infants’ Apgar scores were also recorded.

The women were asked to record their dietary intake for 3 consecutive days during weeks 1, 3, and 5.

Primary Outcome Measures

Serum levels of inflammatory markers (C-reactive protein [CRP]), were the primary outcome measure; secondary outcomes included biomarkers for oxidative stress (nitric oxide [NO], total antioxidant capacity [TAC], total glutathione [GSH], malonaldehyde [MDA]) and pregnancy outcomes.

Key Findings

There was no difference between the groups in mean height, weight, or BMI after the 6-week treatment. Reviewing 3-day diet diaries, there was no significant difference in terms of macronutrient and micronutrient intake between the groups.

After 6 weeks of intervention, compared to the placebo group, women who received probiotic supplementation had significantly reduced CRP (−1.9±4.2 vs +1.1 ± 3.5 mg/L; P=0.004), a marker for inflammation, and MDA, a marker of oxidative stress (−0.1 ± 0.6 vs +0.3 ± 0.7 umol/L; P=0.02). Total antioxidant capacity increased significantly (+70.1 ± 130.9 vs −19.7 ± 124.6 mmol/L; P=0.009) as did GSH (+28.7 ± 61.5 vs −14.9 ± 85.3 umol/L; P=0.02). There was no detectable change in plasma NO levels in either group.

This study demonstrated multiple positive effects, on both mother and child, of supplementation with a relatively low-dose probiotic in pregnant women with gestational diabetes.

Women in the supplementation group had significantly fewer cesarean sections (16.7% vs 40.0%; P=0.04) and lower incidence of hyperbilirubinemic newborns (3.3% vs 30%; P=0.006) and newborn hospitalization (3.3% vs 30%; P=0.006) compared to the placebo group.

Practice Implications

This study demonstrated multiple positive effects, on both mother and child, of supplementation with a relatively low-dose probiotic in pregnant women with gestational diabetes. Positive effects on mothers included improvements in biomarkers of inflammation and oxidative stress, and reduced need for higher-risk surgical interventions during labor. Positive effects on the babies included lower rates of jaundice and hospitalization.

Previous studies of probiotics in other populations have shown positive effects on both inflammatory and oxidative biomarkers,1 and studies in pregnant women with gestational diabetes have shown benefits on inflammatory markers.2 So, it is not surprising to see that probiotics could also improve oxidative biomarkers in this population of pregnant women.

Gestational diabetes is associated with increased oxidative stress due to increased production of reactive oxygen species and advanced glycosylated end products (AGEs).3 That increase in oxidative stress can create an environment where DNA, proteins, and lipids could be at a greater risk for damage. This is particularly relevant during embryonic and fetal development, where there is a high rate of epigenetic imprinting, which can be influenced by the oxidative environment and can also affect the offspring through their adulthood.

Furthermore, it has become clear that the maternal microbial environment is a significant factor of influence in the development of the child’s immune system, as evidenced in studies on the influence of the maternal microbiome on the offspring’s atopic response.4

This study and others point to the relevance of the maternal microbiome to pregnancy outcomes and offspring health. While we are beginning to understand the positive impacts, this is truly just the beginning. In several years, with increasing data pointing to more clear strain-specific impact on biomarkers and health parameters, we will likely look back on this time as one where the prescription of a nonspecific probiotic combination formula was crude. Nevertheless, data clearly demonstrates that even this prescription can provide benefits for mother and child.


This study had a few limitations that could be relevant. First, there were no fecal measurements of bacterial loads, short-chain fatty acids, or microbiological strain analysis. As we know that individuals’ microbiomes are unique, a better understanding of each participant’s microbiome prior to and after the study period could have been helpful, and could also have affirmed compliance to the protocol. Secondly, while this study is relevant to women with gestational diabetes, it would be helpful to understand, through further studies, any positive impact within the general population. Finally, with conflicting results on impact on oxidative and inflammatory markers based upon strains of symbiotic bacteria used, it will be helpful to study strain-specific impacts so that the best probiotic strains can be applied for pregnant women.

Categorized Under


  1. Liu D, Jiang XY, Zhou LS, et al. Effects of probiotics on intestinal mucosa barrier in patients with colorectal cancer after operation: meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(15):e3342.
  2. Jafarnejad S, Saremi S, Jafarejad F, Arab A. Effects of a multispecies probiotic mixture on glycemic control and inflammatory status in women with gestational diabetes: a randomized controlled clinical trial. J Nutr Metab. 2016 (2016):5190846.
  3. Lappas M, Hiden U, Desoye G, et al. The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antiox Redox Signal. 2011;15(12):3061-3100.
  4. Jenmalm MC. The mother-offspring dyad microbial transmission, immune interactions and allergy development (published online ahead of print July 20, 2017). J Intern Med. doi: 10.1111/joim.12652