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Maternal intake of dietary fat pre-programs offspring's gut ecosystem altering long lasting outcomes of immunity in offspring

University of British Columbia

The relationship between the mammalian host and the trillions of microorganisms that colonize their gut during infancy has tremendous potential to impact host physiology, both in health and in disease. The intestinal microbiome lies at the interface of the intestinal and external environment, forming a relationship with intestinal epithelial cells and dietary antigens. Since birth, these microbes help prime host immunity; however, abnormal colonization is implicated in the development of both infectious and autoinflammatory diseases. Consequently, research aims to elucidate how microbes influence immunity and ways to manipulate the microbiome to promote health. Of all the exogenous factors that contribute to the phylogenetic makeup of the microbiome, dietary exposures are the most easily modifiable. Breast milk is the main nutritional source for infants and breast milk fatty acid profiles vary with maternal diet. In North America, n-3 PUFA supplements are advertised as beneficial for infant development. Since n-3 PUFAs can affect inflammation directly and indirectly through the microbiome postnatally, we hypothesized that maternal n-3 PUFA supplementation during lactation would alter the microbiome and immunity in their offspring. We show in a meta-analysis that n-3 PUFAs consumed maternally have no beneficial impact on infant development but may impact immunity. Next, in a clinical study we show that n-3 PUFAs during lactation decrease defensive inflammatory responses in breastmilk and increase anti-inflammatory microbes such as Lactobacillus and Bifidobacteria spp. in neonates at the expense of Enterobacteriaceae. While these anti-inflammatory bacteria are considered beneficial and used in probiotics, we show an inverse relationship between probiotics and mucosal infection risk in toddlers. To understand the mechanism, we gavaged Muc2-/- neonatal mice with L. reuteri and E. coli and examined immune responses. We found that E. coli successfully primed immunity and tolerance, and protected mice from spontaneous colitis whereas L. reuteri increased mortality. Finally, we show that n-3 PUFAs consumed maternally increase enteric infection risk in offspring when combined with unsaturated fats. Overall, the data shown in this thesis does not support the recommendation for n-3 PUFA supplementation during lactation to improve infant health.

Text

2020-07-20

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/75223

Biochemistry and Molecular Biology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/