Perinatal lipid nutrition alters early intestinal development and programs the response to experimental colitis in young adult rats

Abstract

The long-chain polyunsaturated n-6 and n-3 fatty acids are essential nutrients in membrane biogenesis and regulate gene expression via their eicosanoid metabolites. We investigated whether the n-6 and n-3 fatty acid supply as determined by maternal diet alters colonic phospholipid fatty acids, intestinal morphology, and epithelial barrier permeability during milk feeding with lasting effect on mucosal responsiveness to dinitrobenzene sulfonic acid (DNBS)-induced colitis in young adulthood. Female rats were fed diets with 20% energy from safflower oil (SO) or canola oil (CO), or 8% fish oil (FO) plus 2% SO (10% FO) or 18% FO plus 2% SO (20% FO) throughout gestation and lactation and offspring weaned to a standard diet at 21 days of age. At 15 days of age, pups in the 20% and 10% FO groups had lower 20:4n-6 and higher 20:5n-3 and 22:6n-3 in colon phospholipids (P Ͻ 0.01), shorter crypts (P Ͻ 0.05), and higher paracellular permeability than SO or CO groups. At 3 mo of age, male offspring in the FO groups showed lasting reduction of crypt depth and a heightened inflammatory response to DNBS. We demonstrate that early decreased colon 20: 4n-6 with increased n-3 fatty acids impairs intestinal barrier development and sensitizes the colon response to inflammatory insults later in life.n-6 fatty acids; n-3 fatty acids; arachidonic acid; milk fatty acids; intestinal programming; inflammatory bowel disease INFLAMMATORY BOWEL DISEASE (IBD), including Crohn disease and ulcerative colitis, are chronic recurrent inflammatory disorders thought to be precipitated by interplay of environmental and host immune factors in genetically susceptible individuals (40). A pivotal role of environmental factors is clear from the increasing incidence of IBD in recent decades in Western countries (4, 23, 34) and among migrant populations (37,38,43) and the emergence of IBD in populations with previously low prevalence (28).

DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat

“…Appropriate fixation of samples is a key to study both the histopathological damage and visualization of target molecules in tissues by H&E and immunostaining, respectively. Histological scoring of tissues should be performed by experienced individuals who are blinded to the experimental conditions, using fixed criteria set by the individual investigator 11,17 . Myeloperoxidase (MPO) serves as a good marker of inflammation, tissue injury and neutrophil infiltration into gastrointestinal tissues 11 .…”

Towards infant formula biomimetic of human milk structure and digestive behaviour

“…These observations showed that ARA via metabolism of LA was a key determinant in fat mass and globally underlined that LA/LNA ratios during perinatal period could have important programming effect on body composition (Ailhaud et al, 2006). Further proofs of evidence of lipids being involved in programming other functions were obtained in 2010 in animal models (rodents) by two research groups (Innis et al, 2010;Oosting et al, 2010). These results were obtained on non-dairy lipids but paved the way for further investigations on 'dairy lipid structure and programming' conducted just after by Oosting et al (2011Oosting et al ( , 2012Oosting et al ( , 2014.…”

“…The n-6/n-3 ratio in key factor of perinatal nutrition and programming Innis et al (2010) proposed that the increasing incidence of inflammatory bowel disease observed in Western countries over the last decades could be linked to dietary factors including perinatal lipid nutrition. They set the hypothesis that perinatal lipid nutrition affects, directly or indirectly through microbiota modulation, the epithelial barrier function and development, immune system and inflammatory response.…”

“…These characteristics differ among milks (e.g. HM and bovine milk) and are modified after milk technological treatments (heat treatments, homogenization) (Innis et al, 2010;Gallier et al, 2012Gallier et al, , 2013aGallier et al, , 2013bGarcia et al, 2014;Bourlieu et al, 2015b;Le Huërou-Luron et al, 2016). Designing IF that mimic HM digestive behaviour supposes prior characterization of this behaviour.…”

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

“…Additionally, our group had shown that excessive dietary n-3 PUFA (8 and 18% energy fish oil) fed to rat dams during gestation and lactation primed offspring to display impaired intestinal barrier development evident by reduced intestinal crypt length associated with altered permeability and heightened susceptibility to DNBS-colitis at 3 months of age. 20 The objective of this study was to determine if altered intestinal microbial ecosystem is a pre-determining factor that leads to increased susceptibility to colitis in offspring of rat dams fed a diet rich in n-3 PUFA, like fish oil, compared to a diet rich in n-6 PUFA, like safflower oil. We examined the intestinal luminal microbes as well as mucosal immune cell populations of their newborn offspring.…”