Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate

Abstract

Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1β), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1β) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia). Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation.

Importance of the alternative NF-κB activation pathway in inflammation-associated gastrointestinal carcinogenesis

“…In contrast to the findings in humans, mouse models of colitis induced by carrageenan and DSS have demonstrated that classical and alternative NF-B signaling pathways are activated (12,13,81,84) during colonic inflammation. One of the earliest events in IBD is thought to be impairment of enteric mucosal barrier function.…”

“…In contrast, the use of dietary flaxseed to attempt to ameliorate experimental colitis was found to exacerbate DSS-induced colitis in mice, which was associated with an increase in expression of RelB in colonic tissue (84). Together these studies highlight the functional effect that foods may have on NF-B alternative pathway signaling in the gastrointestinal tract.…”

Dietary Intake of Pleurotus eryngii Ameliorated Dextran‐Sodium‐Sulfate‐Induced Colitis in Mice

“…Edible plants have been shown to produce anti‐inflammatory effects in various experimental colitis murine models . However, only very limited research focused on the effects of edible mushrooms on intestinal inflammation.…”

Phytochemicals and Their Potential Usefulness in Inflammatory Bowel Disease

“…Diets exacerbate colitis by increasing the disease activity index, colonic injury, apoptosis, myeloperoxidase, and cytokines like IL‐6 and IL‐1β, and NF‐κB‐related genes, namely Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1. Serum cytokines such as IL‐6, IFN‐γ, IL‐1β, and hepatic cholesterol levels were also increased, indicating systemic toxicity (Zarepoor et al , ).…”