Dietary Flaxseed and Flaxseed Oil Differentially Modulate Aspects of the Microbiota Gut-Brain Axis Following an Acute Lipopolysaccharide Challenge in Male C57Bl/6 Mice.

The microbiota gut-brain axis (mGBA) is an important contributor to mental health and neurological and mood disorders. Lipopolysaccharides (LPS) are endotoxins that are components of Gram-negative bacteria cell walls and have been widely shown to induce both systemic and neuro-inflammation. Flaxseed (Linum usitatissimum) is an oilseed rich in fibre, n3-poly-unsaturated fatty acid (alpha-linolenic acid (ALA)), and lignan, secoisolariciresinol diglucoside, which all can induce beneficial effects across varying aspects of the mGBA. The objective of this study was to determine the potential for dietary supplementation with flaxseed or flaxseed oil to attenuate LPS-induced inflammation through modulation of the mGBA. In this study, 72 5-week-old male C57Bl/6 mice were fed one of three isocaloric diets for 3 weeks: (1) AIN-93G basal diet (BD), (2) BD + 10% flaxseed (FS), or (3) BD + 4% FS oil (FO). Mice were then injected with LPS (1 mg/kg i.p) or saline (n = 12/group) and samples were collected 24 h post-injection. Dietary supplementation with FS, but not FO, partially attenuated LPS-induced systemic (serum TNF-α and IL-10) and neuro-inflammation (hippocampal and/or medial prefrontal cortex IL-10, TNF-α, IL-1ß mRNA expression), but had no effect on sickness and nest-building behaviours. FS-fed mice had enhanced fecal microbial diversity with increased relative abundance of beneficial microbial groups (i.e., Lachnospiraceae, Bifidobacterium, Coriobacteriaceae), reduced Akkermansia muciniphila, and increased production of short-chain fatty acids (SCFAs), which may play a role in its anti-inflammatory response. Overall, this study highlights the potential for flaxseed to attenuate LPS-induced inflammation, in part through modulation of the intestinal microbiota, an effect which may not be solely driven by its ALA-rich oil component.

Active transport of brilliant blue FCF across the Drosophila midgut and Malpighian tubule epithelia.

Under conditions of stress, many animals suffer from epithelial barrier disruption that can cause molecules to leak down their concentration gradients, potentially causing a loss of organismal homeostasis, further injury or death. Drosophila is a common insect model, used to study barrier disruption related to aging, traumatic injury, or environmental stress. Net leak of a non-toxic dye (Brilliant blue FCF) from the gut lumen to the hemolymph is often used to identify barrier failure under these conditions, but Drosophila are capable of actively transporting structurally-similar compounds. Here, we examined whether cold stress (like other stresses) causes Brilliant blue FCF (BB-FCF) to appear in the hemolymph of flies fed the dye, and if so whether Drosophila are capable of clearing this dye from their body following chilling. Using in situ midgut leak and transport assays as well as Ramsay assays of Malpighian tubule transport, we tested whether these ionoregulatory epithelia can actively transport BB-FCF. In doing so, we found that the Drosophila midgut and Malpighian tubules can mobilize BB-FCF via an active transcellular pathway, suggesting that elevated concentrations of the dye in the hemolymph may occur from increased paracellular permeability, reduced transcellular clearance, or both. SUMMARY STATEMENT: Drosophila are able to actively secrete Brilliant blue FCF, a commonly used marker of barrier dysfunction.