Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle

Abstract

Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity.

The prenatal gut microbiome: are we colonized with bacteria in utero?

“…In a similar study, in which 40 pregnant women were repeatedly sampled during gestation, diversity measures of the gut microbiome did not significantly change during pregnancy . These contrasting findings may be explained by heterogeneity in factors that independently influence the maternal gut microbiome, such as maternal insulin resistance and body mass index (BMI) . Larger studies designed to carefully measure factors such as diet, health, antibiotic use, group B Streptococcus status and age will be necessary to further clarify the role of maternal microbiome changes during pregnancy and their influence on the developing foetus.…”

Health impact of the Anthropocene: the complex relationship between gut microbiota, epigenetics, and human health, using obesity as an example

“…The human microbiota gut is formed of phyla, bacterial species and strains, yeasts and other microbes [32]. It is important for maintaining human health, playing a role in proper digestion, synthesis of vitamins, production of neurotransmitters, absorption of minerals, regulating the immune system and inflammatory response while preserving the integrity of the gut epithelial barrier [33][34][35][36][37].…”

Developmental origins of NAFLD: a womb with a clue

“…In addition to maternal obesity and diet, the colonization of the infant gut is also powerfully affected by mode of delivery (Caesarean section versus vaginal delivery), antibiotic use and breastfeeding exposure 118 . An increasing body of epidemiological and animal studies links changes in the infant gut microbiota to allergy, autoimmune disease and obesity risk later in life 118–120 , suggesting that the early neonatal immune system is programmed; however, pathways between specific microbes and their functions remain elusive. The earliest colonizing species are recognized as ‘pioneering microbes’ that educate the developing immune system from a state of hyperstimulation to one of immune tolerance.…”

“…Comparison between humans who are lean or obese shows that bacterial species diversity is reduced in obesity 221,222 ; mucindegrading bacteria Akkermansia muciniphila and antiinflammatory Faecalibacterium prausnitzii are emerging as potential key therapeutic targets 223 , although the mechanisms governing their role in inflammationdriven metabolic disease are yet to be determined. Probiotics and prebiotics have been investigated in both clinical (TABLE 1) and preclinical models; however, as we have reviewed elsewhere 118 , most probiotic trials administered during pregnancy have had limited success in improving maternal and neonatal outcomes. The probiotic Lactobacillus rhamnosus GG, administered in conjunction with Bifidobacterium lactis , has been most commonly studied in pregnancy.…”