Therapeutic Opportunities of GPBAR1 in Cholestatic Diseases

GPBAR1, a transmembrane G protein-coupled receptor for bile acids, is widely expressed in multiple tissues in humans and rodents. In recent years, GPBAR1 has been thought to play an important role in bile homeostasis, metabolism and inflammation. This review specifically focuses on the function of GPBAR1 in cholestatic liver disease and summarizes the various pathways through which GPBAR1 acts in cholestatic models. GPBAR1 mainly regulates cholestasis in a holistic system of liver-gallbladder-gut formation. In the state of cholestasis, the activation of GPBAR1 could regulate liver inflammation, induce cholangiocyte regeneration to maintain the integrity of the biliary tree, control the hydrophobicity of the bile acid pool and promote the secretion of bile HCO3−. All these functions of GPBAR1 might be clear ways to protect against cholestatic diseases and liver injury. However, the characteristic of GPBAR1-mediated proliferation increases the risk of proliferation of cholangiocarcinoma in malignant transformed cholangiocytes. This dichotomous function of GPBAR1 limits its use in cholestasis. During disease treatment, simultaneous activation of GPBAR1 and FXR receptors often results in improved outcomes, and this strategy may become a crucial direction in the development of bile acid-activated receptors in the future.

Gut Microbiota, Combined with Metabolomics, Reveals the Mechanism of Curcumol on Liver Fibrosis in Mice

Background:Liver fibrosis is a reversible pathological process, and its prevention and treatment are of great significance to patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and plasma metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results will help to clarify the relationship between the gut microbiota and metabolites in the process of liver fibrosis.Results:Molecular biological testing found that curcumol could significantly improve the pathological changes of liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s anti-hepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2.Conclusions:When liver fibrosis occurs, the intestinal flora and metabolic network will be altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby regulating liver inflammation.

Supplementation with cyanidin and delphinidin mitigates high fat diet-induced endotoxemia and associated liver inflammation in mice

Short-term supplementation of mice with cyanidin and delphinidin mitigates the metabolic endotoxemia and associated liver inflammation triggered by consumption of a high fat diet (HFD).

Bifidobacterium bifidum Shows More Diversified Ways of Relieving Non-Alcoholic Fatty Liver Compared with Bifidobacterium adolescentis

The occurrence of non-alcoholic fatty liver disease (NAFLD) is closely related to intestinal microbiota disturbance, and probiotics has become a new strategy to assist in alleviating NAFLD. In order to investigate the effect of Bifidobacterium on NAFLD and the possible pathway, a NAFLD model was established by using a high-fat diet (HFD) for 18 weeks. Fourteen strains of Bifidobacterium were selected (seven Bifidobacterium adolescentis and seven Bifidobacterium bifidum) for intervention. The effects of different bifidobacteria on NAFLD were evaluated from liver cell injury, liver fat deposition, liver inflammatory state and liver histopathology, and were taken as entry points to explore the mitigation approaches of bifidobacteria through energy intake, lipid metabolism, glucose metabolism and intestinal permeability. The results showed that Bifidobacterium exerts species-specific effects on NAFLD. B. bifidum exerted these effects mainly through regulating the intestinal microbiota, increasing the relative abundance of Faecalibaculum and Lactobacillus, decreasing the relative abundance of Tyzzerella, Escherichia-Shigella, Intestinimonas, Osillibacter and Ruminiclostridium, and further increasing the contents of propionic acid and butyric acid, regulating lipid metabolism and intestinal permeability, and ultimately inhibiting liver inflammation and fat accumulation to alleviate NAFLD. B. adolescentis exerted its effects mainly through changing the intestinal microbiota, increasing the content of propionic acid, regulating lipid metabolism and ultimately inhibiting liver inflammation to alleviate NAFLD.

Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases

Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut–liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host’s immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut–liver axis in ALD and NAFLD.

Effects of Dietary Pork Fat Cooked Using Different Methods on Glucose and Lipid Metabolism, Liver Inflammation and Gut Microbiota in Rats

Cooking may affect the nutritional value of pork fat, and, nowadays, people have been paying an increasing amount of attention to the method of cooking. In this study, the effects of dietary pork fat cooked using different methods on body metabolism and intestinal microbes were studied in rats. Fat was extracted from pork belly meat cooked using three methods: braising (braising cooking method, BCM), stewing (SCM) and deep fat frying (DCM). The three types of pork fat were added to animal feed, and the effects of each on body weight, glucose and lipid metabolism, liver inflammation and intestinal microbes in rats were compared with the effects of soybean oil-treated feed (SO) and a blank control (BC). Rats in all three groups fed with cooked pork fat exhibited significant increases in body weight compared with the controls across the experimental feeding period. Furthermore, all three types of pork fat led to significant changes in the serum concentrations of triglycerides (TG) and total cholesterol (TC) relative to the controls, with the greatest increases in TG and TC in the BCM and DCM groups, respectively. All three types of pork fat led to significant decreases in serum high-density lipoprotein cholesterol concentrations relative to the controls, with the lowest concentration in the SCM group. All three types of pork fat also led to significant increases in low-density lipoprotein cholesterol concentrations relative to the controls, with the smallest increase in the DCM group. Rats in the SCM group had the highest level of liver fat deposition, followed by those in the BCM, DCM, SO and BC groups. Compared with the controls, the three groups fed with different types of cooked pork fat had significantly lower hepatic expression of nuclear transcription factor kappa B (NF-κB). The expression levels of NF-κB in the DCM and SO groups were significantly lower than those in the other groups. The abundance of Proteobacteria species in the intestines of rats was significantly lower in the BC group than in the other groups fed with cooked pork fat, and the abundance of Bacteroidetes species was significantly lower in the BCM, SCM and DCM groups than in the BC and SO groups. From the changes in the abundance of Firmicutes and Bacteroides, pork fat in the three cooking methods has a certain potential to promote the production of body obesity.