The
essential fatty acids (EFA), n3
alpha-linolenic acid (ALA), and n6
linoleic acid (LA) are of benefit in
diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and
retinal histopathology indices in
streptozotocin (STZ)-induced
type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal
lipoxin A4 (LXA4)-derived from LA-in subjects with
diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 μg/day intraperitoneally on alternate days for 21 days, and their
blood glucose;
lipid profile; plasma, hepatic, and
retinal fatty acid profiles (by gas chromatography);
retinal histology; activities of hepatic and
retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S
rDNA sequencing technology of the fecal samples, and their
short-chain fatty acids and
bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal
fatty acid profiles of subjects with proliferative DR and
LXA4 levels were measured. LA and ALA significantly improved the plasma
glucose and
lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced
acetate and
butyrate levels; and augmented fecal and hepatic concentrations of
cholic acid,
chenodeoxycholic acid, and tauro
ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA,
gamma-linolenic acid,
arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX
enzymes; and
cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low
retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and
retinal index changes seen in T1DM, suggesting that EFAs are of benefit in
diabetes mellitus.