The human gut microbiota plays an important role in the health of immune, metabolic, and endocrine systems. Disturbances in the composition of the microbiome have been implicated in the pathogenesis of obesity, cardiovascular disease, and diabetes. A variety of factors influence the gut microbiome, including host genetics, illness, antibiotic use, dietary patterns, changes in body weight and pregnancy. 

Over the course of a normal pregnancy, the gut microbiome changes significantly. In the first trimester, the gut bacterial composition of pregnant women is similar to that of non-pregnant women, but by the third trimester the maternal microbiome resembles that of people with obesity or metabolic syndrome.¹ An increased abundance of Actinobacteria (now called Actinomycetota) and Proteobacteria (now called Pseudomonadota) phyla, and a reduction in species richness (α-diversity) of the gut microbiome correlates with increases in fat mass, blood glucose, insulin resistance, and circulating pro-inflammatory cytokines in the expectant mother, which serves to maximise nutrient provision to the developing fetus.² However, increased insulin resistance combined with an inability to secrete the additional insulin required to maintain glucose homeostasis can result in the development of gestational diabetes mellitus (GDM) in the mother. Many uncertainties remain regarding precisely when microbiome perturbations develop during pregnancy, and whether the altered microbiota is part of the cause or a consequence of GDM development. 

How Gut Microbial Alterations Might Contribute to GDM Pathogenesis

Women with GDM, and those progressing towards GDM development, show some consistent changes in their gut microbiota, although findings are highly variable between studies. There is a reduction in short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea.³ Short-chain fatty acids (SCFAs) are generated by some bacteria as a metabolic product of dietary fibre fermentation in the large intestine. SCFAs (particularly butyrate, acetate, and propionate) confer numerous benefits on human health by regulating the production of hormones affecting energy intake, energy expenditure, insulin sensitivity, immune activation, and inflammation.⁴ Butyrate reduces gastrointestinal permeability by upregulating the transcription of tight junction proteins and reducing inflammation in colonic epithelial cells. Maintenance of the integrity of the gut barrier minimises the concentration of lipopolysaccharide (LPS) in circulation. LPS is a structural component of Gram-negative bacterial cell walls, which induces an immune-cell response upon translocation from the gut into the human bloodstream (called metabolic endotoxaemia), stimulating proinflammatory cytokine production and the onset of insulin resistance.⁵ Butyrate also acts as a histone deacetylase inhibitor, capable of preventing beta-cell damage through the epigenetic regulation of inflammatory pathways.   

While it is biologically plausible that the disturbed gut microbial composition (dysbiosis) seen in women with GDM amplifies insulin resistance and inflammation, routine testing of the microbiota during pregnancy is currently not warranted. No single GDM-associated microbial signature has been detected,¹ and published studies investigating the microbiome in women with GDM are highly heterogeneous. Most studies varied in the timing of stool sampling, sample collection and storage methods, bacterial sequencing techniques, GDM diagnostic criteria, and diversity in BMI, previous lifestyle changes, and medication use (antibiotics, metformin) of the participants.⁶ 

Maternal Microbiome in GDM Alters the Mother–Milk–Infant Axis

Emerging evidence suggests that GDM may influence the establishment of the offspring’s microbiome. Compared with healthy mothers, GDM-affected mothers transiently produce lower quantities of human milk oligosaccharides (HMOs) in colostrum and mature breastmilk which, in turn, adversely impacts the composition of the infant’s microbiome.⁷ HMOs are not digested in the infant’s small intestine but are a key food source for beneficial gut microbes in the colon.⁸ As gut dysbiosis early in life is associated with increased risks for chronic disease development later in adulthood, modulating the composition of human breastmilk through improvements in postpartum diet quality in mothers with GDM has important therapeutic potential. 

Beneficial Modulation of the Microbiota by Diet and Physical Activity

Diet has a profound effect on the gut microbiota and subsequent risk of GDM, with diets such as the Mediterranean Diet, Dietary Approaches to Stop Hypertension (DASH), and the Alternative Healthy Eating Index (AHEI) being associated with increases in gut microbial diversity and a 15–38% reduction in the relative risk of developing GDM9,10 when consumed pre-pregnancy and during early pregnancy. These dietary patterns focus on a high intake of plant-based foods including vegetables, fruits, legumes, whole grains, and nuts, while minimising intakes of red/processed meat, refined grains, and sugary drinks.  

In women with GDM, there is no single dietary pattern that outperforms others, and personalised dietary counselling from an Accredited Practising Dietitian (APD) is recommended. Personalised dietary advice improves glycaemia in women with GDM and reduces excessive gestational weight gain.¹¹ High fibre, low glycaemic index (GI) carbohydrate-containing foods are encouraged because these foods are consistently associated with an increase in SCFA-producing gut microbes, fewer insulin starts, and lower neonatal birth weight.¹² High fibre, low-GI foods include wholegrain breads, legumes (lentils, chickpeas, kidney beans), oats, barley, natural muesli, most fruits, wholemeal pasta, nuts and seeds, basmati rice, and sweet potato. 

Studies encouraging women with GDM to increase their dietary intake of omega-3 polyunsaturated fatty acids through fish intake or supplements have demonstrated significant increases in beneficial taxa such as Bifidobacterium and Butyricicoccus.¹³ Twice weekly consumption of low-mercury fatty fish such as salmon or sardines will help promote both cardiometabolic and microbiome health. Iron deficiency in women with GDM should be treated with supplements, but very high-dose iron supplements in the absence of deficiency can reduce the presence of SCFA-producing bacteria in the gut.¹⁴ 

Current physical activity in pregnancy recommendations aim for at least 150 minutes of moderate-intensity aerobic activity per week, combined with light resistance exercise on two to three occasions per week.¹⁵ These targets should be encouraged in women with GDM, with an additional recommendation to walk for 10-15 minutes after each main meal to help attenuate postprandial blood glucose excursions. Exercise improves insulin sensitivity, glucose tolerance, and helps prevent excessive weight gain and, indirectly, increases gut microbial diversity and SCFA production.¹⁶ 

Probiotics

Probiotics are defined as “live microorganisms that, when administered in sufficient amounts, confer a health benefit on the host”.¹⁷ Clinical trials have explored the effect of probiotics on GDM incidence and pregnancy outcomes, but the results have been highly inconsistent to date.¹⁸ While probiotic supplementation appears to be safe and well tolerated during pregnancy, study heterogeneity makes results difficult to interpret. Sources of variability across studies include different study designs of varying quality, use of multiple different probiotic strains and doses, and disparate intervention initiation times and durations. Study participant factors which appear to impact probiotic efficacy include genetic background, age, health status, BMI, baseline diet and gut microbial composition, and use of medications. A personalised approach to probiotic supplementation, based on an individual’s unique characteristics, may be efficacious for maternal health in the future but the current evidence base is relatively weak. Diet and exercise interventions are currently superior to probiotics for gut microbiome modulation and the prevention and management of GDM. Probiotics, if used, should only be consumed as an adjunct to rather than as a substitute for lifestyle changes and should be discontinued if there is no benefit observed.