Knowledge, attitudes, and current practices toward lung cancer palliative care management in China: a national survey.

Scope: The present investigation seeks to illuminate the current state and disparities in the knowledge, attitudes, and practices (KAP) among healthcare professionals regarding the management of lung cancer palliative care (LCPC) in China, while simultaneously assessing the prevalence and context of patient-controlled analgesia (PCA) usage in the management of cancer-related pain. Methods: A total of 2093 healthcare practitioners from 706 hospitals across China completed a structured questionnaire that probed various facets of LCPC management. The questionnaire consisted of seven thematic sections, incorporating chi-square tests and Fisher's exact probabilities to statistically assess the discrepancies in KAP among healthcare professionals across different hospital grades. Ordered data distributions among hospital grades were compared using non-parametric Kruskal-Wallis H and Mann-Whitney U tests. Multiple-choice items were subjected to multiple-response cross-tabulation analysis, while the Spearman rank-order correlation coefficient was employed to gauge potential associations among variables. Results: Around 84.2% of the respondents perceived anti-tumor therapy to be of equal importance to palliative care. Statistically significant differences (χ² = 27.402, P = 0.002) in satisfaction levels were observed, with participants from Tertiary hospitals demonstrating higher satisfaction compared to those from Secondary and Primary hospitals. Pain emerged as the most prevalent symptom necessitating LCPC. Major impediments to LCPC adoption included patients' and families' concerns about the safety of long-term palliative care-related drug use. 31.1% of the respondents cited the most frequent rationale for PCA use as cases involving patients who required systemic administration of large opioid doses or exhibited intolerable adverse reactions to opioids. The principal deterrents against the use of PCA for cancer pain management were (1): apprehension about adverse drug reactions due to overdose (2), concern about the potential for opioid addiction, and (3) the anticipated increase in patients' economic burdens. Over the preceding 24-month period, 33.9% of the surveyed healthcare practitioners reported no engagement in either online or offline LCPC-related training initiatives. Conclusion: This study emphasizes the pressing need for comprehensive training in LCPC among Chinese health personnels, particularly focusing on the effective management of cancer pain symptoms.

Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.

Resveratrol improves diabetic kidney disease by modulating the gut microbiota-short chain fatty acids axis in db/db mice.

Diabetic kidney disease is associated with the dysbiosis of the gut microbiota and its metabolites. db/db mice were fed chow diet with or without 0.4% resveratrol for 12 weeks, after which the gut microbiota, faecal short-chain fatty acids (SCFAs), and renal fibrosis were analysed. Resveratrol ameliorated the progression of diabetic kidney disease and alleviated tubulointerstitial fibrosis. Further studies showed that gut microbiota dysbiosis was modulated by resveratrol, characterised by the expansion of SCFAs-producing bacteria Faecalibaculum and Lactobacillus, which increased the concentrations of SCFAs (especially acetic acid) in the faeces. Moreover, microbiota transplantation experiments found that alteration of the gut microbiota contributed to the prevention of diabetic kidney disease. Acetate treatment ameliorated proteinuria, glomerulosclerosis and tubulointerstitial fibrosis in db/db mice. Overall, resveratrol improved the progression of diabetic kidney disease by suppressing tubulointerstitial fibrosis, which may be involved, at least in part, in the regulation of the gut microbiota-SCFAs axis.

Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors in overweight and obese adults: A meta-analysis of randomized controlled trials.

Background and aims: Low-carbohydrate diets (LCD) and low-fat diets (LFD) have shown beneficial effects on the management of obesity. Epidemiological studies were conducted to compare the effects of the two diets. However, the results were not always consistent. This study aimed to conduct a meta-analysis to compare the long-term effects of LCD and LFD on metabolic risk factors and weight loss in overweight and obese adults. Methods: We performed a systematic literature search up to 30 March, 2022 in PubMed, EMBASE, and Cochrane Library. The meta-analysis compared the effects of LCD (carbohydrate intake ≤ 40%) with LFD (fat intake < 30%) on metabolic risk factors and weight loss for ≥6 months. Subgroup analyses were performed based on participant characteristics, dietary energy intake, and the proportions of carbohydrates. Results: 33 studies involving a total of 3,939 participants were included. Compared with participants on LFD, participants on LCD had a greater reduction in triglycerides (-0.14 mmol/L; 95% CI, -0.18 to -0.10 mmol/L), diastolic blood pressure (-0.87 mmHg; 95% CI, -1.41 to -0.32 mmHg), weight loss (-1.33 kg; 95% CI, -1.79 to -0.87 kg), and a greater increase in high-density lipoprotein cholesterol (0.07 mmol/L; 95% CI, 0.06 to 0.09 mmol/L) in 6-23 months. However, the decrease of total cholesterol (0.14 mmol/L; 95% CI, 0.07 to 0.20 mmol/L) and low-density lipoprotein cholesterol (0.10 mmol/L; 95% CI, 0.06 to 0.14 mmol/L) was more conducive to LFD in 6-23 months. There was no difference in benefits between the two diets after 24 months. Subgroup analyses showed no significant difference in the reduction of total cholesterol, low-density lipoprotein cholesterol, and blood pressure between the two diets in participants with diabetes, hypertension, or hyperlipidemia. Conclusion: The results suggest that LCD and LFD may have specific effects on metabolic risk factors and weight loss in overweight and obese adults over 6 months. At 24 months, the effects on weight loss and improvement of metabolic risk factors were at least the same. These indicated that we might choose different diets to manage the overweight and obese subjects. However, the long-term clinical efficacy and effects of various sources of carbohydrates or fat in the two diets need to be studied in the future.

Effects of whole grain intake on glycemic control: A meta-analysis of randomized controlled trials.

AIMS/INTRODUCTION: Although mounting evidence has suggested an inverse association between the intake of whole grains and glycemic control, findings from randomized controlled trials are still conflicting. The current study was carried out to evaluate the effect of medium/long-term whole grain intake on glycemic control in metabolic syndrome and healthy populations. MATERIALS AND METHODS: A literature search was carried out to identify qualified studies up to July 2021. The effects of whole grain consumption on glycemic control were calculated using a fixed effects model. Subgroup analysis was used to study whether grouping factors were important influencing factors of heterogeneity between research results. RESULTS: A total of 32 randomized controlled trials with 2,060 participants were included in the analyses. Whole grain consumption showed a significant inverse regulatory effect on fasting glucose concentration, but no significant effect was found for other glycemic measures, such as fasting insulin, homeostatic model assessment for insulin resistance, glycated hemoglobin and 2-h glucose, in the pooled analysis. Through subgroup analyses, a significant decrease in fasting glucose concentration was observed for studies with a higher whole grain dose, with participants of normal glycemia, and with mixed types of whole grain. CONCLUSIONS: Medium-/long-term whole grain intake reduced the fasting glucose concentration compared with similar refined foods. Appropriate intervention dose and accurate population selection might be the key links for whole grain consumption to exert its glycemic control effect.

Gut microbiota and short chain fatty acids partially mediate the beneficial effects of inulin on metabolic disorders in obese ob/ob mice.

Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. Obese ob/ob mice were fed a standard chow, a low fiber diet (LFD) or a high fiber diet (HFD) for 4 weeks, and the body weight, fecal short chain fatty acids (SCFAs) level, and plasma and liver lipid profiles were analyzed. Oral glucose tolerance testing, and gut microbiota sequencing were also conducted. Dietary inulin improved the dysbiosis of the gut microbiota, attenuated the decrease in phylum Bacteroidetes, repressed the increase of phylum Firmicutes, and led to an increase in the ratio of Firmicutes/Bacteroidetes. At the family level, inulin promoted the expansion of SCFAs-producing Ruminococcaceae and Lachnospiraceae bacteria, which increased the fecal SCFAs concentrations. At the genus level, inulin increased the levels of Bacteroides and Bifidobacteria. Furthermore, our results revealed that there was enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which might be induced by the higher production of SCFAs, and this may underlie the improvements in the disorders of glucose and lipid metabolism seen in mice with added dietary inulin. In conclusion, inulin may ameliorate metabolic disorders by remodeling the gut microbiota and increasing the production of SCFAs, which might be mediated by the ANGPTL4-related signaling pathway. Interventions targeting the gut microbiota warrant further investigation as a novel therapy for metabolic diseases. PRACTICAL APPLICATIONS: Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. In the present study, we investigated the effects of dietary fiber (inulin) on metabolic homeostasis using ob/ob mice. The results of our study demonstrate that inulin-induced remodeling of the gut microbiota resulted in increased production of short chain fatty acids (SCFAs), leading to the enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which improved the glucose and lipid metabolism. Our results suggest that the gut microbiota, SCFAs and ANGPTL4 pathway at least partially mediate the beneficial effects of inulin on metabolic disorders in ob/ob mice.

Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice.

Mounting evidence has linked dietary capsaicin (CAP) consumption to the improvement of glucose homeostasis; however, the underlying mechanisms still need to be further elucidated. Male mice were fed a high-fat diet (HFD) with CAP administration for 8 weeks, gut microbiota, bile acid (BA) profiles and markers for BA, and glucose metabolism were investigated. CAP improved glucose homeostasis partially by enhancing the secretion of glucagon-like peptide 1 (GLP-1). The gut microbiota was remodeled by CAP and was characterized by the increased abundance of Bacteroides genera, which is related with lithocholic acid (LCA) production. LCA is an endogenous agonist of Takeda G-protein coupled receptor 5 (TGR5); it may enhance GLP-1 secretion in intestinal L cells. Meanwhile, antibiotics experiment abolished the effects of CAP on glucose homeostasis and microbiota transplantation experiments demonstrated that the CAP-induced beneficial effects were transferable, indicating that the effects of CAP on glucose homeostasis were largely dependent on the gut microbiota. Additionally, we further identified that the improvements induced by CAP were attenuated by the antagonist of GLP-1 receptor, indicating that the activation of GLP-1 signaling contributes to the CAP-induced improvement in glucose homeostasis.

The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction.

SCOPE: The study investigates the effects of pterostilbene (PTE) on exercise endurance and circadian rhythm in sleep-restricted (SR) mice. METHODS AND RESULTS: The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE (100 mg kg-1 d-1 ) is given once a day. PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters, including creatine kinase and lactate dehydrogenase. It is observed that PTE effectively regained mitochondrial function by improving mitochondrial swelling and maintaining oxidative phosphorylation system-related genes expression, and inhibited the decrease of mitochondrial biogenesis-related genes expression. Furthermore, PTE restores rhythms of AMP-activated protein kinase (AMPK) phosphorylation activity, silent information regulator 1 (SIRT1) deacetylation activity, and SIRT1-mediated peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) deacetylation in SR mice. Finally, the results demonstrate that the AMPK/SIRT1/PGC-1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms, markedly regulating the expression of skeletal muscle clock genes, circadian locomotor output cycles kaput, and brain and muscle arnt-like 1. CONCLUSIONS: PTE ameliorates SR-induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC-1α pathway.

Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling.

OBJECTIVE: Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear. METHODS: A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed. RESULTS: RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota. CONCLUSIONS: These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.

Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system.

BACKGROUND & AIMS: This study aims to investigate the ameliorative effects of resveratrol (RSV) in a high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) rat model, focusing on the gut endocannabinoid system (ECS), regulated by RSV, in the maintenance of gut barrier integrity and inhibition of gut inflammation. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were fed HFD with or without RSV for 6 weeks. The HFD caused increase in body weight, liver index, hepatic lipid accumulation, and inflammation, which was inhibited by RSV. RSV also attenuated gut microbial dysbiosis, with an increase in Akkermansia muciniphila, Ruminococcaceae, and Lachnospiraceae, and a decrease in Desulfovibrio. Moreover, RSV led to a reduction of metabolic endotoxemia and colon inflammation in HFD-fed rats. This was indicated by a decrease in bacterial invasion and translocation along with up-regulation of the mRNA levels of occludin, ZO1, claudin1, and down-regulation of FAK, MyD88, and IRAK4 in the distal colon. Furthermore, RSV inhibited HFD-induced elevation in the expression of cannabinoid receptor type 1 (CB1) mRNA and suppressed CB2 mRNA levels in the colon. The RSV-induced benefits regarding enhanced gut barrier integrity and reduced intestinal permeability were abrogated with a CB1 agonist, ACEA, whereas the inhibitory effect of RSV on the intestinal inflammation was abolished by a CB2 antagonist, AM630. Moreover, microbiota depletion using a cocktail of antibiotics was sufficient to block RSV-induced reduction in intestinal permeability and gut inflammation, as well as the altered mRNA expressions of CB1 and CB2 in the distal colon. CONCLUSIONS: These data indicate that the ECS, particularly the expressions of CB1 and CB2, appears to play a crucial role in the RSV induced anti-NASH effect by maintaining the gut barrier integrity and inhibiting gut inflammation.

Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials.

BACKGROUND: Recent evidence has confirmed that nuts are one of the best food groups at reducing LDL cholesterol and total cholesterol (TC). However, the comparative effects of different types of nuts on blood lipids are unclear. OBJECTIVES: This network meta-analysis of randomized clinical trials aimed to assess the comparative effects of walnuts, pistachios, hazelnuts, cashews, and almonds on typical lipid profiles. METHODS: We conducted literature searches to identify studies comparing ≥2 of the following diets-walnut-enriched, pistachio-enriched, hazelnut-enriched, cashew-enriched, almond-enriched, and control diets-for the management of triglycerides (TGs), LDL cholesterol, TC, and HDL cholesterol. Random-effects network meta-analyses, ranking analyses based on the surface under the cumulative ranking (SUCRA) curves, and sensitivity analyses according to the potential sources of heterogeneity across the included studies were performed for each outcome. RESULTS: Thirty-four trials enrolling 1677 participants were included in this study. The pistachio-enriched diet was ranked best for TG (SUCRA: 85%), LDL cholesterol (SUCRA: 87%), and TC (SUCRA: 96%) reductions. For TG and TC reductions, the walnut-enriched diet was ranked as the second-best diet. Regarding LDL cholesterol reduction, the almond-enriched diet was ranked second best. The pistachio-enriched and walnut-enriched diets were more effective at lowering TG, LDL cholesterol, and TC compared with the control diet. Regarding TG and TC reductions, the pistachio-enriched diet was also more effective than the hazelnut-enriched diet. For TG reduction, the walnut-enriched diet was better than the hazelnut-enriched diet. However, these findings are limited by the low quality of evidence ratings. In addition, the quality of this network meta-analysis was limited by the small number and generally poor reporting of available studies. CONCLUSIONS: The pistachio-enriched and walnut-enriched diet could be better alternatives for lowering TGs, LDL cholesterol, and TC compared with other nut-enriched diets included in this study. The findings warrant further evaluation by more high-quality studies.This network meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019131128.

Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota-Bile Acid-FXR Axis in Type 2 Diabetic db/db Mice.

SCOPE: Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. METHODS AND RESULTS: Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow-fed mice, thereby leading to the accumulation of tauro-ß-muricholic acid (TßMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP-induced suppression of enterohepatic FXR-fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α-hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. CONCLUSIONS: CAP-induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota-BA-enterohepatic FXR axis in db/db mice.

Synergy between dihydromyricetin intervention and irinotecan chemotherapy delays the progression of colon cancer in mouse models.

Colorectal cancer (CRC) is the third highest cause of cancer-related death and the main option for prolonged survival is chemotherapeutic intervention. There is increasing interest in dietary intervention using natural agents to enhance the sensitivity of such invasive chemical treatment. In this study, the chemotherapeutic efficacy of dihydromyricetin (DMY) intervention on treatments involving irinotecan (CPT-11) or gemcitabine (GM) was evaluated in an AOM/DSS-induced colitis-associated colon cancer model and a Min (Apc Min/+) mice model. Our data showed that DMY could promote the CPT-11 effect both in the mouse model of AOM/DSS and Apc Min/+ cancer and had no influence on the GM effect. In AOM/DSS cancer, tumors were sensitive to 100 mg kg-1 DMY chemotherapy under 100 mg kg-1 or 200 mg kg-1 CPT-11. DMY-driven CPT-11 chemotherapy induced enhanced IgG levels and the reduction of Fusobacterium abundance in the gut. In the Min model, CPT-11 with 20 mg kg-1 DMY prevented tumor formation but not with 100 mg kg-1 DMY. Mechanically, chloride ion-dependent CFTR, CLCN4, and CLIC4 signaling are not involved in DMY mediated chemotherapeutic colon tumorigenesis. These results suggested that a suitable dose of DMY could act as a coadjuvant to CPT-11 chemotherapy.

Comparative effects of different whole grains and brans on blood lipid: a network meta-analysis.

PURPOSE: The comparative effects of different whole grains and brans on blood lipid are still not totally elucidated. We aimed to estimate and rank the effects of different whole grains and brans on the control of blood lipid. METHODS: We performed a strategic literature search of PubMed, EMBASE and the Cochrane Library for relevant trials. Both pairwise meta-analyses and network meta-analyses were conducted to compare and rank the intervention strategies of whole grains and brans for the control of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). RESULTS: Fifty-five eligible trials with a total of 3900 participants were included. Cumulative ranking analyses showed that oat bran was the most effective intervention strategy for TC and LDL-C improvements, with significant decreases of - 0.35 mmol/L (95% CI - 0.47, - 0.23 mmol/L) and - 0.32 mmol/L (95% CI - 0.44, - 0.19 mmol/L) in TC and LDL-C compared with control, respectively. In comparison with control, oat was associated with significant reductions in TC by - 0.26 mmol/L (95% CI - 0.36, - 0.15 mmol/L) and LDL-C by - 0.17 mmol/L (95% CI - 0.28, - 0.07 mmol/L), which was ranked as the second best treatment. Barley, brown rice, wheat and wheat bran were shown to be ineffective in improving blood lipid compared with control. CONCLUSIONS: This network meta-analysis suggests that oat bran and oat are ranked higher than any other treatments for the regulations of TC and LDL-C, indicating that increasing oat sources of whole grain may be recommended for lipid control.

SIRT3 Deficiency Promotes High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Correlation with Impaired Intestinal Permeability through Gut Microbial Dysbiosis.

SCOPE: Sirtuin 3 (SIRT3) plays a protective role against nonalcoholic fatty liver disease (NAFLD) by improving hepatic mitochondrial dysfunction. Gut microbiota imbalance contributes to the pathogenesis of NAFLD, yet the underlying mechanism linking SIRT3 with gut microbiota in NAFLD progression remains obscure. METHODS AND RESULTS: Wild-type 129 mice and SIRT3 knockout (SIRT3KO) mice are placed under a chow diet or high-fat diet (HFD) treatment for 18 weeks. HFD resulted in a significantly increased hepatic steatosis and inflammation, which are exacerbated in SIRT3KO mice. The gut microbiota by 16s rRNA gene sequencing and phylogenetic reconstruction of unobserved states analysis are characterized. Lack of SIRT3 facilitates gut microbial dysbiosis in mice following HFD, with increased Desulfovibrio, Oscillibacter, and decreased Alloprevotella. SIRT3 deficiency resulted in an impaired intestinal permeability and inflammation in HFD-fed mice, which can be attenuated by sodium butyrate (NaB). SIRT3KO HFD-fed mice is followed by an increased lipopolysaccharide into the circulation and dysregulated expressions of cannabinoid receptor 1 and 2 in colon and liver, which are significantly associated with the alterations of intestinal microbiota. CONCLUSIONS: SIRT3 deficiency promotes NAFLD progression in correlation with impaired intestinal permeability through gut microbiota dysbiosis.

Crosstalk between gut microbiota and Sirtuin-3 in colonic inflammation and tumorigenesis.

Colorectal cancer (CRC) is a disease involving a variety of genetic and environmental factors. Sirtuin-3 (Sirt3) is expressed at a low level in cancer tissues of CRC, but it is unclear how Sirt3 modulates colonic tumorigenesis. In this study, we found that gut microbiota play a central role in the resistance to CRC tumor formation in wild-type (WT) mice through APC (Adenomatous Polyposis Coli)-mutant mouse microbiota transfer via Wnt signaling. We also found that Sirt3-deficient mice were hypersusceptible to colonic inflammation and tumor development through altered intestinal integrity and p38 signaling, respectively. Furthermore, susceptibility to colorectal tumorigenesis was aggravated by initial commensal microbiota deletion via Wnt signaling. Mice with Sirt3-deficient microbiota transfer followed by chemically induced colon tumorigenesis had low Sirt3 expression compared to WT control microbiome transfer, mainly due to a decrease in Escherichia/Shigella, as well as an increase in Lactobacillus reuteri and Lactobacillus taiwanensis. Collectively, our data revealed that Sirt3 is an anti-inflammatory and tumor-suppressing gene that interacts with the gut microbiota during colon tumorigenesis.

Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.

Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP.

Healthy Subjects Differentially Respond to Dietary Capsaicin Correlating with Specific Gut Enterotypes.

CONTEXT: Previous population studies in evaluating the beneficial effects of capsaicin (CAP) have yielded inconclusive results, and the mechanisms responsible for possible benefit remain unclear. OBJECTIVE: The objective was to assess the effect of dietary CAP on metabolic and immune profiles and its potential associations with gut microbial patterns in healthy adults. DESIGN: In a 6-week controlled feeding trial, subjects were given the weight maintenance diet sequentially contained with 0, 5, 0, and 10 mg/d CAP from chili powder. SETTING AND PARTICIPANTS: The study was conducted in 12 healthy subjects enrolled in Third Military Medical University in Chongqing. MAIN OUTCOME MEASURES: At the end of each period, anthropometric and basal metabolism measures together with blood and fecal samples were collected. Plasma metabolic and inflammatory markers and gut microbial ecology of each subject were subsequently assessed. RESULT: Dietary CAP increased the Firmicutes/Bacteroidetes ratio and Faecalibacterium abundance, accompanied with increased plasma levels of glucagon-like peptide 1 and gastric inhibitory polypeptide and decreased plasma ghrelin level. Further enterotype analysis revealed that these subjects could be clustered into Bacteroides enterotype (E1) and Prevotella enterotype (E2), and the above beneficial effects were mainly obtained in E1 subjects. Moreover, E1 subjects had significantly higher fecal Faecalibacterium abundance and butyrate concentration after CAP interventions than those in E2 subjects. CONCLUSION: Our study showed that gut enterotypes may influence the beneficial effects of dietary CAP, providing new evidence for the personalized nutrition guidance of CAP intervention on health promotion linking with gut microbiota patterns.