How does Maternal Microbiome composition influence offspring metabolic outcomes?
Posted 27th February 2019 by Joshua Sewell
Professor Margaret Morris is Chair and Head of Pharmacology, School of Medical Sciences, University of NSW. Her research explores the underlying brain mechanisms in epilepsy, obesity, diabetes, and the link between obesity and high blood pressure. We recently asked her about her research into obesity and the microbiome.
I studied science at Monash University in Melbourne, Australia, completing a PhD in Medicine. After postdoctoral work in Adelaide and Paris, I took an academic appointment at Deakin University. In 1995 I moved to University of Melbourne, where I began exploring the brain mechanisms involved in food intake and metabolism using animal models of obesity.
In 2005 I joined UNSW, where I am Head of Pharmacology and I lead the Environmental Origins of Obesity group. Current work includes intergenerational transmission of obesity and the psychology of eating, e.g. how does provision of a varied, energy rich diet over-ride the regulatory control mechanisms that should maintain body weight?
Obesity and cognition
I had spent many years exploring the impact of the modern ‘obesogenic’ food environment on appetite control and the hypothalamic chemicals that drive feeding, in addition to the metabolic and behavioural consequences. I was increasingly interested by early onset obesity, so I began researching early life overnutrition, which naturally led me to obesity in mothers. We set up models in rodents and explored the impact on offspring across the lifespan. Then we examined what happens if the father is obese.
Obesity has become a problem largely as we live in an environment surrounded by abundant high fat/high sugar foods that are not only energy dense, but whose consumption can become habitual, where the rewarding value of such foods can over-ride nutritional need.
Homeostatic eating is generally considered to be that required to maintain health, with the right balance of macronutrients. Hedonic eating refers to eating that is influenced by the desire for the food (wanting) and is associated with increased availability and palatability of energy dense food items. Hedonic eating may involve the reward centres of the brain, which include dopaminergic neurons. A major research interest of our group is how provision of a varied, energy rich diet can over-ride the regulatory control mechanisms that should maintain body weight.
The role of gut microbiome in obesity
We are still trying to figure out the role of the gut microbiome in all this – there is clear evidence that the diet can influence the composition of the gut microbiome. In humans there are two major classifications of bacteria called phyla, Bacteriodetes and Firmicutes. Obesity is associated with characteristic shifts in the microbial composition, with a reduction in the ratio of Bacteriodetes to Firmicutes, and weight loss can reverse this shift in bacterial composition (Ley et al, 2006).1
We still don’t know definitively if changes in the gut microbiota due to eating an unhealthy diet can contribute to obesity. Most evidence supporting this hypothesis come from animal studies; for instance, the transfer of faecal material from an obese human can lead to weight gain in a recipient mouse.
Our lab is investigating the impact of diets high in sugar, and fat, on the gut microbiome, and the relationship with changes in cognition.
The maternal microbiome and offspring health
We know that maternal obesity influences the metabolic outcomes for offspring. Alterations in the maternal gut microbiota during critical periods of embryonic, foetal, and early postnatal development may have effects on the offspring gut microbiota, with lifelong consequences for susceptibility to disease. We were thus keen to examine the influence of maternal diet and exercise during pregnancy, on the microbiome composition of both mother and offspring.
A maternal obesogenic diet was associated with higher blood glucose concentrations, final body weight and adiposity in offspring at Post Natal Day 19. Both maternal obesogenic diet and exercise were associated with changes in the gut microbiome (Bhagavata Srinivasan et al),2 with greater effects of diet. Importantly the diet induced changes in the maternal gut microbiota were transferred to their offspring of both sexes. Effects of exercise appeared more marked in those from mothers who consumed a control diet.
In humans, children born to women who were overweight or obese during pregnancy vs. those from normal-weight mothers showed significant differences in gut microbiota composition at 1 month, 6 months (Collado et al)3 and 2 years of age (Galley et al).4 The maternal microbiome is influenced by a range of environmental factors in addition to diet.
The microbiota of a new-born closely matches the microbiome found in maternal stool, vagina, or skin, depending on how they are delivered. The early life microbiome can be modified by antibiotic treatment as well as type of feeding (breast versus formula) and the types of foods and timing of introduction to solid foods.
What this means in the long term is difficult to say at present – we need more research into the long-term impact of the microbiome early in life. As the developmental trajectories of the child are primed during the first 1000 days of life, the host – microbiome interaction my provide a key intervention point for improving health.
Margaret Morris is chair and Head of Pharmacology, School of Medical Sciences, University of NSW. She recently presented at the Microbiome R&D and Business Collaboration Congress: Asia.
1Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444: 1022–3.
2Bhagavata Srinivasan S, Raipuria M, Bahari H, Kaakoush K, MorrisMJ (2018) Impacts of diet and exercise on maternal gut microbiota are transferred to offspring. Frontiers in Endocrinology.
3Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother’s weight on infant’s microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. (2010) 92:1023–30. doi: 10.3945/ajcn.2010.29877.
4Galley JD, Bailey M, Dush CK, Schoppe-Sullivan S, Christian LM. Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS ONE (2014) 9:e113026. doi: 10.1371/journal.pone.0113026.
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