Improving insulin resistance by sulforaphane via activating the Bacteroides and Lactobacillus SCFAs-GPR-GLP1 signal axis.

Background: Insulin resistance (IR) is closely associated with non-alcoholic fatty liver disease (NAFLD), and the gut microbiome contributes to the development of NAFLD. Sulforaphane (SFN) is a phytochemical in cruciferous vegetables that could improve lipid metabolism disorder. However, whether SFN can alleviate IR in NAFLD by regulating the intestinal flora remains unclear. Methods: SFN was administered to high fat diet (HFD)-fed Wistar rats for 10 weeks. Gut microbiota was analysed by 16S rRNA sequencing and the short chain fatty acids (SCFAs) by gas chromatography. The expression of tight junction protein and the numbers of Lactobacillus, Bacteroides and Bifidobacterium were determined by qPCR. The expression of G-protein-coupled receptor 41/43 (GPR41/43) was determined by western blot. A randomized controlled trial (RCT) was conducted in NAFLD patients with broccoli seed tablets (rich in SFN, 42 mg d-1) as intervention for 12 weeks. Thirty-six volunteers with abnormal glucose before the broccoli seed tablet treatment were selected in the intervention group to analyze their blood glucose, insulin, homeostasis model assessment-insulin resistance index (HOMA-IRI), homeostasis model assessment-insulin sensitivity index (HOMA-ISI) and glucagon-like peptide (GLP-1). Results: SFN reduced blood glucose and HOMA-IRI while increasing insulin sensitivity in HFD rats. SFN reduced glycogen synthase kinase 3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK) activity, and phosphorylation of serine residues of IRS-2 induced by HFD. SFN reshaped the gut microbiota composition of HFD-induced rats and, especially, increased the content of Bacteroidaceae, Lactobacillaceae and Bifidobacteriaceae, which are related to the improvement from SFN of the blood glucose and HOMA-IRI. The increased numbers of Bacteroides and Lactobacillus were the targets of SFN to enhance the expression of tight junction proteins ZO-1 and occludin, thereby lowering lipopolysaccharide content to reduce inflammation, ultimately alleviating IR. Bacteroides and Lactobacillus produced SCFAs, which activated GPR41/43 to secrete GLP1. Moreover, it was also confirmed in RCT that SFN intervention increased the level of GLP1 in NAFLD patients, which was positively correlated with the reduction of blood glucose and HOMA-IR. Conclusions: SFN alleviated IR in NAFLD via the Bacteroides and Lactobacillus SCFAs-GPR41/43-GLP1 axis and protected the intestinal mucosal barrier to decrease inflammation.

Association of Pro-Inflammatory Diet, Smoking, and Alcohol Consumption with Bladder Cancer: Evidence from Case-Control and NHANES Studies from 1999 to 2020.

BACKGROUND AND PURPOSE: Diet might be a modifiable factor in preventing cancer by modulating inflammation. This study aims to explore the association between the dietary inflammatory index (DII) score and the risk of bladder cancer (BC). METHODS: A total of 112 BC patients and 292 control subjects were enrolled in a case-control trial. Additionally, we tracked a total of 109 BC patients and 319 controls, whose propensity scores were obtained from the Nutrition Examination Survey (NHANES) database spanning from 1999 to 2020. The baseline index and dietary intake data were assessed using a food frequency questionnaire (FFQ). DII scores were calculated based on the dietary intake of 20 nutrients obtained from participants and categorized into four groups. The association between the inflammatory potential of the diet and BC risk was investigated using multivariate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: High DII scores were associated with a pro-inflammatory diet and a higher risk of BC, with higher DII scores positively associated with a higher risk of BC (quartiles 4 vs. 1, ORs 4.89, 95% CIs 2.09-11.25 p < 0.001). Specifically, this might promote BC development by inducing oxidative stress and affecting DNA repair mechanisms. This result was consistent with the NHANES findings (quartiles 4 vs. 1, ORs 2.69, 95% CIs 1.25-5.77, p = 0.006) and further supported the association of pro-inflammatory diet and lifestyle factors with the risk of BC. CONCLUSIONS: Diets with the highest pro-inflammatory potential were associated with an increased risk of BC. By adjusting lifestyle factors, individuals might effectively lower their DII, thereby reducing the risk of developing BC. The results are consistent with the NHANES cohort.