Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn’s Disease

Abstract

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn’s disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.

Advances in free fatty acid profiles in gestational diabetes mellitus

“…Diets high in n-3 intake can cause reduced cytokine production and lower cardiovascular disease risk factors [ 63 ]. However, western diets tend to be low in fiber and rich in total fat, rich in n-6 PUFAs as well as saturated fats, including hydrogenated vegetable fat (HVF, rich in trans fat) and interesterified fat (IF), making the n-6/n-3 PUFA ratio high [ 64 , 65 ]. Modern diets tend to increase n-6 intake and decrease n-3 intake owing to the increase in processed food consumption, widespread use of hydrogenated vegetable oils, and impact of industrialized agriculture.…”

Crohn’s disease: Why the ileum?

“…Oral feeding with n-3 PUFAs in SAMP1/Yit mice ameliorated the histological features of ileitis, and decreased addressin molecule expression (MAdCAM-1) as well as lymphocyte infiltration in the ileum[ 127 ]. To that extent, oral supplementation with linseed oil rich in α-linolenic acid (n-3 PUFAs), in a physically active murine model, reduced inflammation after oral challenge with AIEC[ 128 ]. However, oral n-3 PUFAs supplementation has not shown definitive results in patients with CD[ 129 ].…”

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment

“…Microbial dysbiosis and impaired mucosal barrier are pivotal features in IBD pathogenesis, and PUFAs might influence IBD by altering microbial balance and maintaining mucosal barrier. Flaxseed supplementation and ω-6-rich fatty acids have been associated with promoting microbial dysbiosis in CD and altering mucosal barrier functions ( 100 , 171 ). Supplementation of DPA increases gut microbial diversity and changes microbial composition in DSS-induced colitis mice ( 102 ).…”