Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely associated with hyperglycemia, abnormal lipid profiles, chronic low-grade inflammation and gut dysbiosis. Dietary intervention plays a crucial role in the control of diabetes. Flaxseed oil (FO), a plant-derived omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), is rich in α-linolenic acid (ALA) which has been proved to benefit for chronic metabolic disease. However, the exact effects of dietary FO on T2DM remains largely unclear. METHODS: In the present study, SD rats were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); DM with CO group (DM/CO); PF with FO group (PF/FO); DM with FO group (DM/FO). A diabetic rat model was generated by a single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NA). After 5 weeks of intervention, rats were euthanized and associated indications were investigated.
RESULTS: Dietary FO significantly reduced fasting blood glucose (FBG), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-17A and malondialdehyde (MDA), compared to control group, respectively. Moreover, body mass (BM) and superoxide dismutase (SOD) in DM/FO group were dramatically increased respectively, compared with those in DM/CO group. But insulin (INS) and homeostasis model assessment of insulin resistance (HOMA-IR) remained no significant difference between DM/CO group and DM/FO group. Sequencing analysis of gut microbiota showed a reduction in the relative abundance of Firmicutes and Blautia, as well as a reduction in the ratio of Bacteroidetes-Firmicutes in DM/FO group compared to DM/CO group. An elevation in the relative abundance of Bacteroidetes and Alistipes were detected in DM/FO group. Acetic acid, propionic acid and butyric acid belonging to short chain fatty acids (SCFAs) as gut microbiota metabolites, were dramatically increased after FO intervention. Correlation analysis revealed that the relative abundance of Firmicutes and Blautia were positively correlated with IL-1β, TNF-α, IL-6, IL-17A or LPS, respectively. Additionally, Bacteroidetes and Alistipes were negatively correlated with LPS.
CONCLUSIONS: Taken together, dietary FO ameliorated T2DM via suppressing inflammation and modulating gut microbiota, which may potentially contribute to dietary control of diabetes.
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Key Points
Type 2 diabetes mellitus (T2DM) is closely associated with hyperglycemia, abnormal lipid profiles, chronic low-grade inflammation and gut dysbiosis. The present study aimed to assess the effects of dietary flaxseed oil (FO) and mechanisms related to inflammation and gut microbiota in diabetic rats.
FO was effective in alleviation of T2DM, which may be due to the suppression of inflammation and restoration of gut dysbiosis, potentially providing a theoretical foundation as an inexpensive intervention for prevention and treatment of T2DM. Consumption of ω-3 PUFAs are beneficial for chronic metabolic diseases including T2DM via anti-inflammation and suppressing oxidative stress in clinical and experimental studies.
LPS derived from pathogenic bacteria, a causal link between gut microbiota and systemic low-grade inflammation, translocates to liver and binds to TLR-4 to induce inflammatory cascade reaction to ultimately lead to diabetes mellitus. The data showed that plasma LPS was notably decreased after FO intervention, indirectly demonstrating that integrity and permeability of intestinal mucosa barriers were improved to alleviate peripheral endotoxemia. The possible mechanism of anti-inflammation is that ALA in FO diet-mediated GPR120 activation and β-arrestin 2 recruitment in the inhibition of TLR4 and TNF-α downstream signaling.
Growing evidences have demonstrated the gut microbiota play a critical role in the development of T2DM. In this study, at phylum level, we found that Bacteriodetes and Firmicutes were the most dominant in all four groups, which was similar to the human intestinal flora. Firmicutes played a major role in absorbing calories from the diet and storing fat in gut cells. In present study, a decrease of Firmicutes after FO treatment revealed that FO may attenuate diabetes via reducing Firmicutes-involved in energy absorption. In addition, the ratio of Firmicutes–Bacteroidetes was increased in diabetic group, suggesting a characteristics of micro-ecological disorder in intestinal microbes. Importantly, dietary FO intervention restored this ratio, demonstrating that dietary FO positively shaping the host microbial ecosystem.
At the genus level, Blautia is a gram-positive, anaerobe bacterium belonging to the family Lachnospiraceae, which was thought to take part in the development of glucose metabolism disturbances. This study found that the abnormal elevated Blautia in diabetes was restored by FO intervention. FO treatment significantly regulated the abundance of Alistipes which belongs to family Rikenellaceae. The above findings suggested that Alistipes may be involved in the improvement of diabetes.
FO supplementation also significantly increased propionic acid and butyric acid which showed decreased in diabetes group but without significant difference, suggesting that dietary FO possessed the ability to increase SCFAs within or without diabetes.
This study highlighted that dietary FO supplementation ameliorated T2DM induced by STZ-NA via anti-inflammation, modulating composition of gut microbiota and gut microbiota metabolite acetate in rat, suggesting that it can potentially serve as inexpensive interventions for the prevention and treatment of diabetes.