Propionate and butyrate are proven capable of decreasing plasma cholesterol. However, their undesired odor and unpleasant smell limit their direct application as a dietary supplement. In contrast, their respective triacylglycerols tributyrin (Tb) and tripropionin (Tp) are odorless and can be directly used as healthy supplements. In view that no study has investigated the relative biological potency of Tb and Tp, the present study was designed to compare the effects of Tp and Tb on plasma cholesterol and gut microbiota using hypercholesterolemic hamsters as a model. Male golden hamsters were randomly allocated to 6 groups fed one of the following 6 diets, namely, low-cholesterol diet (LCD), high-cholesterol diet (HCD), HCD + 0.5% Tp (LTp), HCD + 1% Tp (HTp), HCD + 0.5% Tb (LTb), and HCD + 1% Tb (HTb). Results showed that Tb administration at 1% could significantly reduce plasma total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDLC), and the ratio of non-HDLC to HDLC, whereas Tp supplementation had no effect. Mechanistically, Tb but not Tp could decrease plasma cholesterol by increasing the excretion of fecal bile acids via upregulating gene expression of cholesterol 7α-hydroxylase (CYP7A1) and liver X receptor alpha (LXRα). In addition, Tb supplementation at 1% could increase the gut microbiota diversity, reduce the ratio of Firmicutes/Bacteroidetes and favorably increase the abundance of beneficial microbial genera Bifidobacterium. In conclusion, dietary Tb supplementation was more effective than Tp in mitigating hypercholesterolemia by increasing the excretion of fecal bile acids and favorably modulating gut microbiota.

Long-term excessive salt intake is a risk factor for hypertension, but its impact on lipid metabolism and gut microbiota remains poorly understood. This study aims to evaluate the effects of inadequate or excessive salt intake on lipid metabolism and gut microbiota composition, and explore the underlying relationship between these effects. Male Syrian golden hamsters were randomly assigned to six groups and fed diets with sodium chloride levels of 0.4, 0.8, 3.0 (a normal dose), 6.0, 12.0 or 24.0 g/kg for nine weeks. Lipid levels in plasma, liver and feces were measured, and fresh feces were analyzed via 16s rRNA gene sequencing. Results showed that neither inadequate nor excessive salt intake altered plasma lipids. However, excessive salt intake led to a dose-dependent increase in liver lipid accumulation. Additionally, it significantly modified gut microbiota composition at the family and genus levels. Notably, higher salt doses reduced both the relative abundance of Allobaculum and fecal short-chain fatty acids (SCFA) concentrations, with a positive correlation being observed between the two. These findings suggest that excessive salt intake aggravates hepatic lipid accumulation, likely by modulating gut microbiota involved in SCFA production.

Oxidized cholesterol (OXC) is a harmful dietary substance. Although the consumption of OXC has been associated with colonic inflammation, related underlying mechanisms are still limited. We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model. Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC. Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon, accompanied by an increase in the abundance of 2 mucus-degrading bacteria, namely Akkermansia muciniphila and Bacteroides acidifaciens. Consistently, oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium (DSS)-induced colitis mice and facilitated bacteria infiltration in the colon. The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice, suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis. Finally, the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins. These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.

Gut health is the foundation of overall health. Inflammatory bowel disease (IBD) including Crohn’s disease and ulcerative colitis is a kind of chronic relapsing and idiopathic immune dysbiosis in the intestinal tract. Recent studies have highlighted the effects of various dietary components on the progress of IBD. Mounting evidence has demonstrated that both dietary lipids and gut microbiome-derived lipids play a crucial role in gut health. They can directly or indirectly change the composition of gut microbiota, modulate the metabolism of colonic epithelial cells, influence the integrity of gut barrier and regulate the immune function. This review aims to define the key classes of dietary lipids and microbial-derived lipids, elucidate the interaction of these lipids with gut microbiota, discuss their effects on the intestinal homeostasis, and provide the future perspective in the research of gut health.

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia, which play crucial roles in the management of type 2 diabetes. Protocatechuic acid (PCA) is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon. The present study investigated the inhibitory mechanism of PCA on α-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo. Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of α-glucosidase. Driven by hydrogen bonds and van der Waals interactions, PCA reversibly bound with α-glucosidase to form a stable α-glucosidase-PCA complex in a spontaneous manner. The computational simulation found that PCA could insert into the active cavity of α-glucosidase and establish hydrogen bonds with catalytic amino acid residues. PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues. PCA also exhibited postprandial hypoglycemic capacity in diabetic mice. This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

Cardiovascular disease (CVD) is a leading cause of deaths and is a growing epidemic worldwide. Atherosclerosis, the primary cause of heart diseases and stroke, is associated with vascular inflammation and accumulation of lipids and fibrous elements in the arteries. Recently, blood trimethylamine-N-oxide (TMAO) has been identified as an independent risk factor for CVD in humans. TMAO is mainly derived from dietary trimethylamine (TMA)-containing nutrients via the bioconversion of gut microbiota and hepatic flavin monooxygenases (FMOs). Both in vivo and in vitro studies have revealed that TMAO promotes atherogenesis by exacerbating vascular inflammation, impairing vascular functions and disturbing cholesterol homeostasis at multiple levels. This review summarizes the current research on the microbiota-dependent generation pathway of TMAO, the associations of TMAO with atherosclerosis, and the potential dietary interventions to reduce the TMAO-associated risk of CVD.