Diet primary driver
Aagaard and her colleagues at OHSU’s Oregon National Primate Research Center have focused for several years on the role a high fat maternal diet, rather than just obesity, plays on the health of the infant. They have shown that in the primate the diet is the primary driver which perturbs the developing infant’s epigenome (the molecules and chemical modifications that decorate the human genome after the basic pattern of genomic DNA is established.)
In the study using non-human primates, the team observed dams and their offspring (both lean and obese) exposed to a high fat diet, and compared them to control diet exposed animals for up to 1 year of age.
“This enabled us to differentiate the impact of maternal obesity versus high fat diet on the developing fetus,” said Aagaard. “We observed an interesting phenomenon, about 1/3 of the dams did not become obese despite many years of exposure to a high fat diet.”
Building on these findings, Aagaard and her colleagues now sought to distinguish whether it was the diet or obesity which appeared to drive changes in the dams and their offspring’s microbiome. They found that it was a high fat diet, rather than obesity, that defined the microbiome communities of the gut.
High fat, low fat diet
The finding is key, she said. “A woman can more easily alter her diet from high fat to low fat, but safely and realistically cannot change her obesity status in the short course of pregnancy.”
Additionally, the team observed that Campylobacter (bacteria attributed to diarrheal illness in humans) was eradicated in the offspring with either maternal or post-natal, high-fat diet.
“In humans, this group of bacteria causes diarrheal illnesses, but in primates many species are commensal (neutral, not disease causing),” said Aagaard. “This suggests that a bacteria being pathogenic or disease causing may not always be because it mutates or changes, but rather our dietary changes over time evolve our microbial community such that what was once harmless becomes harmful.”
Pregnancy and lactation may be crucial windows for establishing the earliest colonizers in our microbiome, she said.
More importantly, it suggests that the association between obesity and the microbiome is more affect than cause.
“Based on our well-grounded observations in primates, it appears that a high fat diet drives changes in the intestinal microbiome. This in turn is associated with obesity some—but not all—of the time,” said Aagaard. “In fact, even lean animals on a high fat diet were observed to have an altered microbiome. Importantly, being born and breastfed to a high fat diet fed mom persistently and significantly changes the offspring’s microbiome. This is true even when a healthy control diet is given after weaning.”
Other authors on this report include: Jun Ma, Amanda L. Prince, David Bader, Dr. Min Hu, Dr. Radhika Ganu, Dr. R. Alan Harris, all of Baylor; Karalee Baquero, Peter Blundell, Dr. Antonio E. Frias and Dr. Kevin L. Grove, all of the Oregon National Primate Research Center at Oregon Health & Science University in Beaverton.
Funding for this work was provided by the National Institutes of Health (P51 OD011092, DP21DP2OD001500, NR014792, R01DK079194 and R01DK089201).