Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance

Abstract

Keywords: colonic inflammation, infant immunity, intestinal microbiota, maternal diets, n-6 and n-3 polyunsaturated fatty acidsOur previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of na€ ıve immune cells. To identify such mechanisms, gut microbes and na€ ıve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8C T cells, CD4C Foxp3C T cells and arginaseC M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

“…Using a genetic model of n-3 PUFA supplementation (Fat-1), Kaliannan et al demonstrated that elevated n-3 PUFA levels enhance intestinal production and secretion of intestinal alkaline phosphatase (IAP), which induces changes in the gut bacteria composition, resulting in decreased LPS production and gut permeability and, ultimately, in reduced metabolic endotoxemia and inflammation [183]. N-3 PUFA deficiency during development (over gestation and lactation) also alters the normal trajectory of intestinal microbe establishment in the intestine of offspring, with lowered bacterial density, a decreased ratio of Firmicutes to Bacteroidetes, and a decrease in several other dominant microbes [184]. These data suggest that n-3 PUFA levels modulate microbiota composition and activity during development.…”

Mucosal Interactions between Genetics, Diet, and Microbiome in Inflammatory Bowel Disease

“…The role of host diet–gene interactions is also modulated by epigenetic effects; hypothetical effects have been proposed for n -3 LCPUFAs on cell proliferation, survival, and immunity ( 291 – 293 ). Maternal exposure to LCPUFA is known to alter the gut microbiota in offspring; n -3 fish oil increases Bacteroidetes; other fish oil diets increase pathobionts linked to altered immunity, namely B. wadsworthia, Enterococcus faecium , and B. fragilis , and n -6 safflower oil increases Firmicutes ( 294 – 296 ). PUFA (i.e., n -6) exposure can also induce epigenetic protective effects (transferrable to GF mice via FMT) in young animals against DSS colitis ( 297 ).…”

Infant formula interface and fat source impact on neonatal digestion and gut microbiota

“…Because polyunsaturated FA are essential nutrients and that the infant depends exclusively either on the maternal milk or the formula for an adequate n‐6 and n‐3 FA supply, their physiological effects have been largely described. Beneficial effects of n‐3 FA on intestinal disorders have been consistent in different experimental models of intestinal inflammation although a dual role, pro/anti‐inflammatory, was recently highlighted depending on the quality and quantity of dietary fat and the location of inflammed intestine . By contrast, less is known on the impacts of milk fat‐induced changes in formula lipid droplet composition and structure on neonatal digestive physiology.…”