Ground flaxseed reverses protection of a reduced fat diet against Citrobacter rodentium-induced colitis.

Key Findings

Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBD) with an increasing global health burden. The gut microbiota, or community of microorganisms which reside in the gastrointestinal tract, is shaped by dietary intake and plays an important role in IBD pathogenesis and treatment. Dietary intake of n-3 PUFA increases the abundance of beneficial commensal Lactobacillus in diet-induced obese mice and administration of n-3 PUFA promotes growth and adherence of the probiotic strain Lactobacillus casei, strain Shirota to cultured Caco-2 cells. Flaxseed supplementation has been reported to increase markers of a healthy gut barrier. This study assessed host responses of mice provided flaxseed in HF or reduced fat (RF) diets prior to Citrobacter rodentium-induced colitis. The demonstrate a strong protective effect of a RF diet against intestinal inflammation, dysbiosis and pathogen burden during colitis induced by the mouse-specific, non-invasive enteric bacterium C. rodentium. However, ground flaxseed supplementation in the setting of a RF diet exacerbated infection-induced colitis despite higher levels of intestinal n-3 PUFA and cecal SCFA. The exacerbating effects of ground flaxseed on colitis were observed only in the setting of a RF diet, but not in animals fed a HF diet. Supplementation of a RF mouse diet with ground flaxseed altered expression of the cytokine IL-22 in response to an enteric bacterial infection. The findings presented in this study also show that ground flaxseed can impact the composition of the gut microbiota, which could serve, at least in part, to explain how flaxseed exacerbates colitis. For instance, flaxseed in a RF diet depleted Akkermansia muciniphila, an abundant mucin-degrading bacterium thought to protect the host from intercurrent enteric infections through competitive exclusion. The findings of this study highlight the importance of dietary background in modulating host responses to dietary supplements, particularly in the setting of an intercurrent enteric infection and gut mucosal inflammation.

ABSTRACT

Flaxseed is high in omega-3 polyunsaturated fatty acids, fiber and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high fat (HF; ~36 %kcal) or reduced fat (RF; ~12 %kcal) diet. After weaning, C57BL/6 mice (n=8-15/treatment) were fed ground flaxseed (7g/100g diet) with either HF (HF Flx) or RF (RF Flx) diets for four weeks prior to infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids and cecal short-chain fatty acids were compared over a 14-day infection period. A RF diet protected against C. rodentium-induced colitis, whereas a RF Flx diet increased pathogen burden, exacerbated gut inflammation and promoted gut dysbiosis. Compared with a RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although a RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation.