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.

Polycystic ovary syndrome (PCOS) represents a common endocrine—metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague–Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-fed CON group (FO/CON), (c) PF with letrozole-induced PCOS model (MOD) group (PF/MOD), and (d) FO-fed MOD group (FO/MOD). All rats were fed a standard diet. After 3 weeks of modeling and subsequent 8 weeks of treatment, the rats in diverse groups were euthanized and associated indications were investigated. The results showed that dietary FO ameliorated the disorder of estrous cycle and ovarian morphology. In parallel, dietary FO improved the sex steroid hormone disturbance (luteinizing hormone/follicle-stimulating hormone, estrogen, testosterone, and progesterone), body weights, dyslipidemia, and insulin resistance. Moreover, FO treatment improved plasma and ovary inflammatory interleukin (IL)-1β, IL-6, IL-10, and IL-17A, tumor necrosis factor-α, and monocyte chemoattractant protein-1. Additionally, FO intervention significantly modulated the composition of gut microbiota and vaginal microbiota by increasing the abundances of Allobaculum, Lactobacillus, Butyrivibrio, Desulfovibrio, Bifidobacterium, Faecalibacterium, Parabacteroides as well as decreasing the abundances of Actinobacteria, Bacteroides, Proteobacteria, and Streptococcus, the ratio of Firmicutes/Bacteroidetes. A decrease in plasma lipopolysaccharide level and an increase in short-chain fatty acids, including acetic acid, propionic acid, butyric acid and pentanoic acid, were determined after dietary FO supplementation. Correlation analysis revealed close relationships among sex steroid hormones, inflammation, and gut/vaginal microbiota. Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones—microbiota—inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.

Alcoholic liver disease (ALD) represents a chronic wide-spectrum of liver injury caused by consistently excessive alcohol intake. Few satisfactory advances have been made in management of ALD. Thus, novel and more practical treatment options are urgently needed. Flaxseed oil (FO) is rich in α-linolenic acid (ALA), a plant-derived n-3 polyunsaturated fatty acids (PUFAs). However, the impact of dietary FO on chronic alcohol consumption remains unknown. In this study, we assessed possible effects of dietary FO on attenuation of ALD and associated mechanisms in mice. Firstly, mice were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); alcohol-fed (AF) with CO group (AF/CO); PF with FO group (PF/FO); AF with FO group (AF/FO). Each group was fed modified Lieber-DeCarli liquid diets containing isocaloric maltose dextrin a control or alcohol with corn oil and flaxseed oil, respectively. After 6 weeks feeding, mice were euthanized and associated indications were investigated. Body weight (BW) was significantly elevated in AF/FO group compared with AF/CO group. Dietary FO reduced the abnormal elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in chronic ethanol consumption. Amelioration of these parameters as well as liver injury via HE staining in dietary FO supplementation in ALD demonstrated that dietary FO can effectively benefit for the protection against ALD. To further understand the underlying mechanisms, we investigated the inflammatory cytokine levels and gut microbiota. A series of inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-10, were determined. As a result, TNF-α, IL-1β and IL-6 were decreased in AF/FO group compared with control group; IL-10 showed no significant alteration between AF/CO and AF/FO groups (p > 0.05). Sequencing and analysis of gut microbiota gene indicated that a reduction of Porphyromonadaceae and Parasutterella, as well as an increase in Firmicutes and Parabacteroides, were seen in AF group compared with PF control. Furthermore, dietary FO in ethanol consumption group induced a significant reduction in Proteobacteria and Porphyromonadaceae compared with AF/CO group. Dietary FO ameliorates alcoholic liver disease via anti-inflammation and modulating gut microbiota, thus can potentially serve as an inexpensive interventions for the prevention and treatment of ALD.

Chronic low-grade inflammation is regarded to an important signature of atherosclerosis (AS). Macrophage (Mψ) and related polarization have been demonstrated to play a crucial role in the occurrence and development of AS inflammation. Butyrate, a bioactive molecule produced by the intestinal flora, has been increasingly demonstrated to exhibit a vital role for regulating the inflammation in chronic metabolic diseases. However, the effectiveness and multiple anti-inflammation mechanisms of butyrate on AS still need to be further understood.ApoE^−/−mice fed with high-fat diet as AS model were administered with sodium butyrate (NaB) for 14 weeks of treatment. Our results showed that the atherosclerotic lesion in the AS group was dramatically reduced after NaB intervention. Moreover, deteriorated routine parameters of AS including body weights (BWs), low-density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC) were significantly reversed by NaB administration. Abnormal elevated plasma and aorta pro-inflammatory indicators including interleukin (IL)-1β, IL-6, IL-17A, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), as well as reduced anti-inflammatory IL-10 in plasma were respectively rectified after NaB administration. Consistently, accumulated Mψ and associated imbalance of polarization in the arota were attenuated with NaB treatment. Importantly, we demonstrated that the suppression of Mψ and associated polarization of NaB was dependent on binding G-protein coupled receptor (GPR) and inhibiting histone deacetylase HDAC3. Moreover, we found that intestinal butyrate-producing bacteria, anti-inflammatory bacteria and intestinal tight junction protein zonula occludens-1 (ZO)-1 may contribute to this effectiveness. Intriguingly, according to transcriptome sequencing of atherosclerotic aorta, 29 elevated and 24 reduced miRNAs were found after NaB treatment, especially miR-7a-5p, suggesting that non-coding RNA may possess a potential role in the protection of NaB against AS. Correlation analysis showed that there were close complicated interactions among gut microbiota, inflammation and differential miRNAs. Collectively, this study revealed that dietary NaB may ameliorate atherosclerotic inflammation by regulating Mψ polarization via GPR43/HDAC-miRNAs axis inApoE^−/−mice.

The microbiome–gut–brain (MGB) axis, which regulates neurological and cognitive functions, plays an essential role in schizophrenia (SCZ) progression. Dietary inulin could be a novel strategy for the treatment of SCZ due to its modulating effects on the gut microbiota. In this study, the effects of inulin on mice with SCZ were studied. As indicated by the behavioural tests, expression of neurotransmitters, inflammatory indicators, and brain morphology, inulin administration ameliorated aberrant behaviours (locomotor hypoactivity, anxiety disorders and depressive behaviours, and impaired learning and spatial recognition memory) and effectively reduced neuroinflammation and neuronal damage. In addition, inulin improved intestinal integrity and permeability, as indicated by the elevated expression of tight junction proteins (p < 0.05). The results of 16S rRNA sequencing and analysis showed that inulin increased the abundance of Lactobacillus and Bifidobacterium, which were negatively correlated with 5-hydroxytryptamine and inflammatory cytokines and positively correlated with brain-derived neurotrophic factor (BDNF). Inulin caused a reduction in Akkermansia that was positively correlated with inflammatory cytokines and negatively correlated with BDNF. These results suggested that dietary inulin modulated the gut microbiota and exerted anti-inflammatory effects in mice though the MGB axis, which further ameliorated SCZ. Therefore, the results of this study provide a potential explanation for inulin intervention in the treatment of SCZ.

Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO. A total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17 A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants. The results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation. Collectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.