Involvement of Bile Acid Metabolism and Gut Microbiota in the Amelioration of Experimental Metabolism-Associated Fatty Liver Disease by Nobiletin.

Metabolism-associated fatty liver disease (MAFLD), a growing health problem worldwide, is one of the major risks for the development of cirrhosis and liver cancer. Oral administration of nobiletin (NOB), a natural citrus flavonoid, modulates the gut microbes and their metabolites in mice. In the present study, we established a mouse model of MAFLD by subjecting mice to a high-fat diet (HFD) for 12 weeks. Throughout this timeframe, NOB was administered to investigate its potential benefits on gut microbial balance and bile acid (BA) metabolism using various techniques, including 16S rRNA sequencing, targeted metabolomics of BA, and biological assays. NOB effectively slowed the progression of MAFLD by reducing serum lipid levels, blood glucose levels, LPS levels, and hepatic IL-1ß and TNF-α levels. Furthermore, NOB reinstated diversity within the gut microbial community, increasing the population of bacteria that produce bile salt hydrolase (BSH) to enhance BA excretion. By exploring further, we found NOB downregulated hepatic expression of the farnesoid X receptor (FXR) and its associated small heterodimer partner (SHP), and it increased the expression of downstream enzymes, including cholesterol 7α-hydroxylase (CYP7A1) and cytochrome P450 27A1 (CYP27A1). This acceleration in cholesterol conversion within the liver contributes to mitigating MAFLD. The present findings underscore the significant role of NOB in regulating gut microbial balance and BA metabolism, revealing that long-term intake of NOB plays beneficial roles in the prevention or intervention of MAFLD.

The dose-response relationship of fruit and vegetable intake and risk of type 2 diabetes among rural China: The Henan Rural Cohort study.

AIMS: To explore the dose-response relationship of fruit and vegetable (F&V) intake and type 2 diabetes (T2D) risk in rural China. METHODS: A total of 38798 adults were recruited from the Henan Rural Cohort Study. F&V intake was assessed by a validated food-frequency questionnaire. Logistic regression and restricted cubic splines analysis were conducted to calculate the odds ratio (OR) for T2D relative to F&V intake and investigate the dose-response relationship. RESULTS: Higher intake of fruit or combined F&V was in connection with a lower risk of T2D, after adjusting for multiple confounders. After analyzing the dose-response relationship, we found that the odds of T2D decreased significantly with fruit consumption ≥ 260 g/day or F&V intake between 600 and 1000 g/day. And in subgroup analysis, we found that the negative correlation between fruit consumption and T2D was more pronounced in non-current smokers and non-current drinkers. CONCLUSIONS: High intake of fruit alone or combined F&V is related to a reduced risk of T2D in rural China. Fruit intake ≥ 260 g/day and total F&V consumption of 600-1000 g/day should be encouraged to promote good health.

Association of intestinal microbiota markers and dietary pattern in Chinese patients with type 2 diabetes: The Henan rural cohort study.

Studies on intestinal microbiota in Chinese type 2 diabetes mellitus (T2DM) patients are scarce and correlation studies with dietary intake are lacking. The case-control study included 150 participants (74 T2DM patients and 76 controls) and microbiome analysis was performed using 16S rDNA sequencing. Principal component analysis was used to determine dietary patterns and correlation analysis was used to evaluate the associations between microbiota diversity, T2DM indicators and dietary variables. Compared to controls, the T2DM group had different gut flora characteristics, including lower alpha diversity, higher Firmicutes/Bacteroidetes ratios, statistically significant beta diversity and other specific bacterial species differences. Gut microbiota was associated with several diabetes-related metabolic markers including HOMA2-ß, fasting plasma glucose, HbA1c and fasting insulin. Significant associations were also observed between dietary intake pattern and gut flora. The animal foods pattern scores were positively correlated with the relative abundance of the phylum Fusobacteria, and the vegetarian diet pattern scores were positively correlated with the relative abundance of the phylum Actinobacteria. Phylum Actinobacteria mediated the association of vegetarian diet pattern with fasting insulin and HOMA2-ß (all P < 0.05). Composition of intestinal microbiota in Chinese T2DM patients differs from that of control population, and the intestinal flora is affected by dietary intake while being associated with several diabetes-related metabolic markers. The gut microbiota may play an important role in linking dietary intake and the etiology of T2DM.

Association between Dietary Protein Intake and Type 2 Diabetes Mellitus in Chinese Rural Elderly Population: A Matched Case-Control Study.

The purpose of this study was to examine the association between dietary protein intake and the risk of type 2 diabetes mellitus (T2DM) among a Chinese rural elderly population. We used the demographic and dietary information of adults over age 65 in the Henan Rural Cohort Study to identify and pair 950 T2DM patients with healthy controls in a 1 : 1 matched case-control study. Dietary data was collected through a Food Frequency Questionnaire. A multivariate logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of T2DM risk according to protein intake. After adjustment for confounding factors, higher intake of total protein was negatively associated with T2DM risk in the total population (extreme-tertile OR=0.75, 95% CI: 0.58-0.93) and women (extreme-tertile OR=0.84, 95% CI: 0.47-0.93). Multivariate-adjusted ORs for the risk of T2DM in the highest compared with lowest tertile of plant protein intake in the total population and in women were 0.86 (95% CI: 0.60-0.84) and 0.58 (95% CI: 0.36-0.95), respectively. Our results suggest that the protein intake, especially plant protein, has a significant association with the risk of T2DM in rural elderly populations, and the sources of protein may be also important in future guidelines.

Association of plant-based diet and type 2 diabetes mellitus in Chinese rural adults: The Henan Rural Cohort Study.

AIMS/INTRODUCTION: Studies have found that a plant-based diet was associated with a lower risk of type 2 diabetes, but evidence is scarce on such associations in China. The aim of this study was to investigate whether a plant-based diet is related to a lower risk of type 2 diabetes among Chinese adults. MATERIALS AND METHODS: A total of 37,985 participants were enrolled from the Henan Rural Cohort Study. An overall plant-based diet index (PDI) was created by assigning positive and reverse scores to 12 commonly consumed food groups. Multivariate logistic regression models and restricted cubic spline analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: After multivariable adjustment, the risk of type 2 diabetes was inversely associated with the PDI (extreme-quartile OR = 0.88, 95% CI: 0.79-0.98; P = 0.027), the risk associated with a 1 standard deviation (SD) increase in PDI was 4% lower (95% CI, 0.93-1.00; P trend  = 0.043) for type 2 diabetes. Moreover, the odds of type 2 diabetes was decreased with an increment of PDI after fitting restricted cubic splines (P trend  < 0.01). CONCLUSIONS: Among Chinese populations, diets higher in plant foods and lower in animal foods were associated with a reduced risk of type 2 diabetes.