Investigating the causal relationship between gut microbiota and gastroenteropancreatic neuroendocrine neoplasms: a bidirectional Mendelian randomization study.

Background: The interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis. Methods: Two-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran's Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs. Results: We identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora. Conclusion: The present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

Exploring the effects of whey protein components on the interaction and stability of cyanidin-3-O-glucoside.

BACKGROUND: Anthocyanins are susceptible to degradation due to external factors. Despite the potential for improved anthocyanin stability with whey protein isolate (WPI), the specific effects of individual components within WPI on the stability of anthocyanins have yet to be studied extensively. This study investigated the interaction of WPI, ß-lactoglobulin (ß-Lg), bovine serum albumin (BSA), and lactoferrin (LF) with cyanidin-3-O-glucoside (C3G), and also considered their effects on stability. RESULTS: Fluorescence analysis revealed static quenching effects between C3G and WPI, ß-Lg, BSA, and LF. The binding constants were 1.923 × 103 L · mol⁻¹ for WPI, 24.55 × 103 L · mol⁻¹ for ß-Lg, 57.25 × 103 L · mol⁻¹ for BSA, and 1.280 × 103 L · mol⁻¹ for LF. Hydrogen bonds, van der Waals forces, and electrostatic attraction were the predominant forces in the interactions between C3G and WPI and between C3G and BSA. Hydrophobic interaction was the main binding force in the interaction between C3G and ß-Lg and between C3G and LF. The binding of C3G with WPI, ß-Lg, BSA, and LF was driven by different thermodynamic parameters. Enthalpy changes (∆H) were -38.76 kJ · mol⁻¹ for WPI, -17.59 kJ · mol⁻¹ for ß-Lg, -16.09 kJ · mol⁻¹ for BSA, and 39.50 kJ · mol⁻¹ for LF. Entropy changes (∆S) were -67.21 J · mol⁻¹·K⁻¹ for WPI, 3.72 J · mol⁻¹·K⁻¹ for ß-Lg, 37.09 J · mol⁻¹·K⁻¹ for BSA, and 192.04 J · mol⁻¹·K⁻¹ for LF. The addition of C3G influenced the secondary structure of the proteins. The decrease in the α-helix content suggested a disruption and loosening of the hydrogen bond network structure. The presence of proteins enhanced the light stability and thermal stability (stability in the presence of light and heat) of C3G. In vitro simulated digestion experiments demonstrated that the addition of proteins led to a delayed degradation of C3G and to improved antioxidant capacity. CONCLUSION: The presence of WPI and its components enhanced the thermal stability, light stability, and oxidation stability of C3G. Preheated proteins exhibited a more pronounced effect than unheated proteins. These findings highlight the potential of preheating protein at appropriate temperatures to preserve C3G stability and bioactivity during food processing. © 2024 Society of Chemical Industry.

The mediating role of negative emotions in the relationship between smoking and health-related quality of life among Chinese individuals: A cross-sectional study.

INTRODUCTION: Although the negative impact of smoking on health has been confirmed in various studies, few have explored psychological factors mediating the relationship between smoking and health-related quality of life (HRQOL). This study aimed to investigate the relationship between smoking and HRQOL in the Chinese population and the mediating role of negative emotions (NEs). METHODS: Survey data were derived from a cross-sectional study conducted in China from 20 June to 31 August 2022. We recruited participants from 148 cities across the country using a stratified multistage sampling method. The HRQOL of the dependent variable was measured using the Chinese version of European Quality of Life-5 Dimensions (EQ-5D-5L). The Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), and Perceived Stress Scale (PSS-4) were used to measure NE parameters including depression, anxiety, and perceived stress, as the intermediate variables. A multiple parallel mediation model was used to analyze the mediating role of NEs in smoking and HRQOL. RESULTS: A total of 21916 valid questionnaires were collected, of which 3010 (13.7%) and 18906 (86.3%) were categorized into smokers and non-smokers, respectively. The HRQOL (EQ-VAS score) of smokers (71.70 ± 23.08) was lower than that of non-smokers (73.69 ± 21.32), whereas the depression and anxiety levels of smokers were higher than those of non-smokers (all p<0.001). Moreover, smoking, NEs (depression and anxiety), and HRQOL showed pairwise correlations. According to the mediation analysis, depression (ß= -0.461; 95% BCa CI: -0.664 - -0.268) and anxiety (ß= -0.279; 95% BCa CI: -0.435 - -0.138) mediated the relationship between smoking and HRQOL after adjusting for demographic and life factors. CONCLUSIONS: These findings emphasize the necessity of studying the interaction between smoking, HRQOL, and Nes, and complementing the research on the impact of psychological factors on the HRQOL of smokers. Public health activities should focus on mental health and take targeted measures for the prevention, treatment, and rehabilitation of smokers.

High-fat diet induces intestinal mucosal barrier dysfunction in ulcerative colitis: emerging mechanisms and dietary intervention perspective.

The incidence of ulcerative colitis (UC) is increasing worldwide, but its pathogenesis remains largely unclear. The intestinal mucosa is a barrier that maintains the stability of the body's internal environment, and dysfunction of this barrier leads to the occurrence and aggravation of UC. A high-fat diet (HFD) contains more animal fat and low fiber, and accumulating evidence has shown that long-term intake of an HFD is associated with UC. The mechanism linking an HFD with intestinal mucosal barrier disruption is multifactorial, and it typically involves microbiota dysbiosis and altered metabolism of fatty acids, bile acids, and tryptophan. Dysbiosis-induced metabolic changes can enhance intestinal permeability through multiple pathways. These changes modulate the programmed death of intestinal epithelial cells, inhibit the secretion of goblet cells and Paneth cells, and impair intercellular interactions. Gut metabolites can also induce intestinal immune imbalance by stimulating multiple proinflammatory signaling pathways and decreasing the effect of anti-inflammatory immune cells. In this review, we critically analyze the molecular mechanisms by which an HFD disrupts the intestinal mucosal barrier (IMB) and contributes to the development of UC. We also discuss the application and future direction of dietary intervention in the treatment of the IMB and prevention of UC.

Gastroesophageal reflux disease and oral symptoms: A two-sample Mendelian randomization study.

Background: The association between Gastroesophageal reflux disease (GERD) and oral symptoms has been reported in observational studies, but the causality of GERD to oral symptoms remained unknown. We aimed to assess the causal effect of GERD on five oral symptoms (mouth ulcers, toothache, loose teeth, bleeding gums, and periodontitis) using the two-sample Mendelian randomization (MR) method. Methods: Summary-level statistics for GERD and five oral symptoms were obtained from large-scale genome-wide association studies. Rigorous quality control of genetic instruments was conducted before MR analysis. Several analytical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, maximum likelihood, and robust adjusted profile score (RAPS) were utilized, and the results of IVW were taken as the main results. The MR-Egger intercept test, Cochran's Q test, and leave-one-out test were used as sensitivity analysis for quality control. Results: After Bonferroni, IVW detected a significant effect of GERD on mouth ulcers (OR = 1.008, 95% CI = 1.003-1.013, p = 0.003), loose teeth (OR = 1.009, 95% CI = 1.005-1.012, p = 9.20 × 10-7), and periodontitis (OR = 1.229, 95% CI = 1.081-1.398, p = 0.002). Consistent patterns of associations were observed across several MR models and sensitivity analysis found little evidence of bias. Nominal significant associations were observed in toothache and bleeding gums (p < 0.05), and heterogeneity was detected. Conclusion: Our MR analyses supported the positive causal effect of GERD on oral symptoms, especially for mouth ulcers, loose teeth, and periodontitis. Our findings might shed light on the mechanism of oral disease and might imply that oral care should be enhanced in patients with GERD.