The impact of the world's first regulatory, multi-setting intervention on sedentary behaviour among children and adolescents (ENERGISE): a natural experiment evaluation.

BACKGROUND: Regulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world's first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils. METHODS: With a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status. RESULTS: Longitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings. CONCLUSIONS: This regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.

Protocatechuic acid alleviates TMAO-aggravated atherosclerosis via mitigating inflammation, regulating lipid metabolism, and reshaping gut microbiota.

Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. As a natural phenolic acid, protocatechuic acid (PCA) is abundant in various plant foods. The present study investigated the effect of PCA on TMAO-aggravated atherosclerosis in ApoE-/- mice. The mice were randomly divided into five groups and fed one of the following five diets for 12 weeks: namely a low-fat diet (LFD), a western diet (WD), a WD + 0.2% TMAO diet (WDT), a WDT + 0.5% PCA diet (WDT + LPCA), and a WDT + 1.0% PCA diet (WDT + HPCA). Results demonstrated that dietary TMAO exacerbated the development of atherosclerosis by eliciting inflammation and disturbing lipid metabolism. The diet with PCA at 1% reduced TMAO-induced aortic plaque by 30% and decreased the levels of plasma pro-inflammatory cytokines. PCA also improved lipid metabolism by up-regulating the hepatic gene expression of peroxisome proliferator-activated receptor alpha (PPARα). In addition, PCA supplementation enhanced fecal excretion of fatty acids and decreased hepatic fat accumulation. PCA supplementation favorably modulated gut microbiota by increasing the α-diversity with an increase in the abundance of beneficial genera (Rikenella, Turicibacter, Clostridium_sensu_stricto and Bifidobacterium) and a decrease in the abundance of the harmful Helicobacter genus. In summary, PCA could alleviate the TMAO-exacerbated atherosclerosis and inflammation, improve the lipid metabolism, and modulate gut microbiota.

National nutrition surveillance programmes in 18 countries in South-East Asia and Western Pacific Regions: a systematic scoping review.

Objective: To identify and analyse ongoing nutrition-related surveillance programmes led and/or funded by national authorities in countries in South-East Asian and Western Pacific Regions. Methods: We systematically searched for publications in PubMed® and Scopus, manually searched the grey literature and consulted with national health and nutrition officials, with no restrictions on publication type or language. We included low- and middle-income countries in the World Health Organization South-East Asia Region, and the Association of Southeast Asian Nations and China. We analysed the included programmes by adapting the United States Centers for Disease Control and Prevention's public health surveillance evaluation framework. Findings: We identified 82 surveillance programmes in 18 countries that repeatedly collect, analyse and disseminate data on nutrition and/or related indicators. Seventeen countries implemented a national periodic survey that exclusively collects nutrition-outcome indicators, often alongside internationally linked survey programmes. Coverage of different subpopulations and monitoring frequency vary substantially across countries. We found limited integration of food environment and wider food system indicators in these programmes, and no programmes specifically monitor nutrition-sensitive data across the food system. There is also limited nutrition-related surveillance of people living in urban deprived areas. Most surveillance programmes are digitized, use measures to ensure high data quality and report evidence of flexibility; however, many are inconsistently implemented and rely on external agencies' financial support. Conclusion: Efforts to improve the time efficiency, scope and stability of national nutrition surveillance, and integration with other sectoral data, should be encouraged and supported to allow systemic monitoring and evaluation of malnutrition interventions in these countries.

Cholesterol Oxidation Products: Potential Adverse Effect and Prevention of Their Production in Foods.

Cholesterol oxidation products (COPs) are a group of substances formed during food processing. COPs in diet is a health concern because they may affect human health in association with the risk of various diseases including atherosclerosis, Alzheimer's disease, age-related macular degeneration, diabetes, and chronic gastrointestinal inflammatory colitis. Production of COPs in foods can be affected by many factors such as temperature, pH, light, oxygen, water, carbohydrates, fatty acids, proteins, and metal cations. The key issue is preventing its generation in foods. Some COPs can also be produced in vivo by both nonenzymatic and enzymatic-catalyzed oxidation reactions. Currently, a number of natural antioxidants such as catechins, flavonoids, and other polyphenols have been proven to inhibit the generation of COPs. In addition, measures taken during food processing can also minimize the production of COPs, such as the Maillard reaction and marinating food with plant polyphenol-rich seasonings. In conclusion, a comprehensive approach encompassing the suppression on COPs generation and implementation of processing measures is imperative to safeguard human health against the production of COPs in the food chain.

Mangiferin alleviates trimethylamine-N-oxide (TMAO)-induced atherogenesis and modulates gut microbiota in mice.

Trimethylamine-N-oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis. Mangiferin is a bioactive xanthone initially extracted from mango (Mangifera indica). The present study aimed to investigate the effect of mangiferin on TMAO-induced atherogenesis in mice fed a high-choline diet. Female ApoE-/- mice were randomly divided into three groups and fed either a control diet, a high-choline diet with 1% free choline, or an experimental diet with 1% free choline plus 0.5% mangiferin for 15 weeks. Our results showed that a high-choline diet elevated plasma TMAO levels, accelerated atherogenesis, promoted cholesterol accumulation, and reduced the generation of short-chain fatty acids (SCFAs) by gut microbes. Mangiferin alleviated inflammation, and lowered plasma total cholesterol levels by facilitating the elimination of neutral and acidic sterols in feces, resulting in a 16.7-29.0% reduction in aortic atherosclerotic lesions. Notably, mangiferin could favorably remodel the composition of the gut microbiota by fostering the growth of the beneficial taxa Akkermansia, Parabacteroides, and Bifidobacteriaceae, while reducing the relative abundance of the pathogenic genus Helicobacter. This modulation led to a decrease in plasma lipopolysaccharide levels, enhanced the production of total SCFAs by gut microbes, and reduced susceptibility to atherosclerosis. In conclusion, mangiferin exhibited its ability to alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.

D-pinitol ameliorated H2O2-induced oxidative damage in PC12 cells and prolonged the lifespan by IIS pathway in Caenorhabditis elegans.

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H2O2-induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans, DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aß in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16, skn-1, hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3, ctl-1, ctl-2, gst-4, hsp-16.1, and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future.

Cultural adaptations and methodological innovations to group model building for the systems actions to reduce malnutrition in all its forms in Southeast Asian countries and China (SYSTAM CHINA-SEACS International Consortium) project.

BACKGROUND: Group Model Building (GMB) is a participatory system dynamics method increasingly used to address complex public health issues like obesity. GMB represents a set of well-defined steps to engage key stakeholders to identify shared drivers and solutions of a given problem. However, GMB has not yet been applied specifically to develop multi-duty interventions that address multiple inter-related issues such as malnutrition in all its forms (MIAIF). Moreover, a recent systematic review of empirical applications of a systems approach to developing obesity interventions found no published work from non-western, low- and middle-income countries (LMICs). In this paper we describe adaptations and innovations to a common GMB process to co-develop systemic MIAIF interventions with Chinese decision-makers. METHODS: We developed, piloted and implemented multiple cultural adaptations and two methodological innovations to the commonly used GMB process in Fang Cheng Gang city, China. We included formal, ceremonial and policy maker engagement events before and between GMB workshops, and incorporated culturally tailored arrangements during participant recruitment (officials of the same seniority level joined the same workshop) and workshop activities (e.g., use of individual scoring activities and hand boards). We made changes to the commonly used GMB activities which enabled mapping of shared drivers of multiple health issues (in our case MIAIF) in a single causal loop diagram. We developed and used a 'hybrid' GMB format combining online and in person facilitation to reduce travel and associated climate impact. RESULTS: Our innovative GMB process led to high engagement and support from decision-makers representing diverse governmental departments across the whole food systems. We co-identified and prioritised systemic drivers and intervention themes of MIAIF. The city government established an official Local Action Group for long-term, inter-departmental implementation, monitoring and evaluation of the co-developed interventions. The 'hybrid' GMB format enabled great interactions while reducing international travel and mitigating limitations of fully online GMB process. CONCLUSIONS: Cultural and methodological adaptations to the common GMB process for an Asian LMIC setting were successful. The 'hybrid' GMB format is feasible, cost-effective, and more environmentally friendly. These cultural adaptations could be considered for other Asian settings and beyond to address inter-related, complex issues such as MIAIF.

Effect of tea catechins on gut microbiota in high fat diet-induced obese mice.

BACKGROUND: Tea catechins have been shown to have beneficial effects on the alleviation of obesity, the prevention of diabetes, and the amelioration of metabolic syndrome. The purpose of the present work is to explore the underlying mechanisms linking the intestinal microbiota and anti-obesity benefits of green tea, oolong tea, and black tea catechins in C57BL/6J mice fed with a high-fat diet (HFD). RESULTS: The results indicated that, after the dietary intake of three tea catechins, obesity and low-grade inflammation were significantly alleviated. Hepatic steatosis was prevented, and this was accompanied by the upregulation of the mRNA and protein expressions of hepatic peroxisome proliferator-activated receptor α (PPARα). Metagenomic analysis of fecal samples suggested that the three tea catechins similarly changed the microbiota in terms of overall structure, composition, and protein functions by regulating the metabolites, facilitating the generation of short-chain fatty acids (SCFAs), and repressing lipopolysaccharides. CONCLUSION: The anti-obese properties of three tea catechins were partially mediated by their positive effect on gut microbiota, hepatic steatosis alleviation, and anti-inflammatory activity. © 2023 Society of Chemical Industry.

Dietary Oxidized Cholesterol Aggravates Chemically Induced Murine Colon Inflammation and Alters Gut Microbial Ecology.

Western diet with a higher intake of fat and cholesterol has been claimed as an intestinal inflammation trigger. Human diet contains both cholesterol and oxidized cholesterol. Oxidized cholesterol has been claimed to be associated with various inflammation diseases, but its effects on colitis and gut microbiome remain largely unknown. The present study was the first time to investigate the effect of the oxidized cholesterol on gut microbiota and dextran sodium sulfate-induced colitis using mice as a model. The results showed that oxidized cholesterol promoted colitis by exacerbating bleeding, body weight decrease, colon shortening, gut barrier damage, oxidative stress, and gut inflammation, whereas non-oxidized cholesterol had no effect. Meanwhile, oxidized cholesterol could adversely modulate the gut microbiota by increasing the relative abundance of pro-inflammatory bacteria (including Escherichia-Shigella and Bacteroides) and decreasing that of beneficial bacteria (Lachnospiraceae_NK4A136_group and Odoribacter). In addition, oxidized cholesterol significantly reduced the production of fecal short-chain fatty acids in colitis mice. It was concluded that oxidized cholesterol was a potential dietary factor of gut dysbiosis.

Effects of Thermally-Oxidized Frying Oils (Corn Oil and Lard) on Gut Microbiota in Hamsters.

Repeated reuse of frying oil raises health concerns due to the accumulation of oxidative products after each frying cycle. Gut microbiota is integral in lipid metabolism and immune regulation. The present study was designed to investigate the effects of thermally-oxidized corn oil and lard on gut microbiota in relation to atherosclerosis, inflammatory cytokines, and plasma lipids. Male Golden Syrian hamsters were randomly divided into four groups and fed one of four diets containing fresh corn oil (CF), oxidized corn oil (CO), fresh lard (LF), and oxidized lard (LO), for six weeks. CO and LO were prepared by deep-frying potatoes in corn oil or lard for seven days. Results indicated that oxidized oil and lard caused the loss of species diversity and richness of gut microbiota. Feeding CO and LO also reduced the body and adipose tissue weights, associated with genus Acetatifactor and Allobaculum. Plasma triacylglycerols significantly increased by 51% in the CO and 35% in the LO group compared with that in their CF and LF counterparts, respectively. CO could also affect the abundance of specific bacteria genera: Bacteroides, Barnesiella, Acetatifactor, Allobaculum, Clostridium_IV, Clostridium_XIVa, Coprococcus, Lactococcus, Paraprevotella, Parasutterella, and Oscillibacter. In addition, CO and LO could adversely remodel gut composition and affect intestinal production of short-chain fatty acids, pro-inflammatory biomarkers (LPS and IL-6), anti-inflammatory biomarker IL-10, and atherosclerotic progression. It was concluded that frying oil could adversely modulate the gut microbiota and exacerbate the atherosclerosis at least in a hypercholesterolemia hamster model.

Effects of hawthorn seed oil on plasma cholesterol and gut microbiota.

BACKGROUND: Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. METHODS: Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. RESULTS: HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. CONCLUSIONS: HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation.

Gut microbiota mediate melatonin signalling in association with type 2 diabetes.

AIMS/HYPOTHESIS: It has been shown that melatonin plays a general beneficial role in type 2 diabetes in rodents but its role in humans is controversial. In the present study, we investigated the association between serum melatonin and type 2 diabetes risk in a southern Chinese population in a case-control study. We also examined the role of gut microbiota in this relationship. METHODS: Individuals with type 2 diabetes (cases) and healthy individuals (controls) (n=2034) were recruited from a cross-sectional study and were matched for age and sex in a case-control study. The levels of serum melatonin were measured and the association between serum melatonin and type 2 diabetes risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n=120) in which gut microbial 16S rRNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach. RESULTS: Higher levels of serum melatonin were significantly associated with a lower risk of type 2 diabetes (OR 0.82 [95% CI 0.74, 0.92]) and with lower levels of fasting glucose after adjustment for covariates (ß -0.25 [95% CI -0.38, -0.12]). Gut microbiota exhibited alteration in the individuals with type 2 diabetes, in whom lower levels of serum melatonin, lower α- and ß-diversity of gut microbiota (p<0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (linear discriminant analysis [LDA] >2.0) were found. Seven genera were correlated with melatonin and type 2 diabetes-related traits; among them Bifidobacterium was positively correlated with serum lipopolysaccharide (LPS) and IL-10, whereas Coprococcus was negatively correlated with serum IL-1ß, IL-6, IL-10, IL-17, TNF-α and LPS (Benjamini-Hochberg-adjusted p value [false discovery rate (FDR)] <0.05). Moreover, altered metabolites were detected in the participants with type 2 diabetes and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR<0.05). Similarly, a significant correlation was found between Trp metabolites and inflammation factors, such as IL-1ß, IL-6, IL-10, IL-17, TNF-α and LPS (FDR<0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict type 2 diabetes status (AUC=0.804). CONCLUSIONS/INTERPRETATION: A higher level of serum melatonin was associated with a lower risk of type 2 diabetes. Gut microbiota-mediated melatonin signalling was involved in this association; especially, Bifidobacterium- and Coprococcus-mediated Trp metabolites may be involved in the process. These findings uncover the importance of melatonin and melatonin-related bacteria and metabolites as potential therapeutic targets for type 2 diabetes.

Dietary variety relates to gut microbiota diversity and abundance in humans.

PURPOSE: We aim to investigate the relationship between gut microbiota and dietary variety in a Chinese population using Dietary Variety Score (DVS), an index of dietary variety, as little has studied the relationship of dietary variety and gut microbiota in a general population. METHODS: In this cross-sectional study, recruited participants were conducted with face-to-face interview to collect information on 24-h food intake and dietary consumption using a valid food frequency questionnaire. Subjects (n = 128) were divided as high and low DVS groups by the median of DVS after rigorously matching for confounding factors. The gut microbiota was assessed by 16S rRNA sequencing and the correlations between key phylotypes and DVS, Index of Nutritional Quality (INQ) and clinical indices were examined using generalized linear model in negative binomial regression. RESULTS: Higher score of DVS, INQVB6, INQVE and INQZn exhibited higher α-diversity. DVS was correlated with INQ and six genera. Among the DVS-correlated genera, Turicibacter, Alistipes and Barnesiella were positively correlated with INQVE, INQZn and INQCu, individually or in combination, while Cetobacterium was negatively correlated with INQCu, INQZn and INQVE. The abundance of Coprococcus and Barnesiella increased with the elevated cumulative scores of INQVE, INQVB6 and INQZn. The combination of Alistipes, Roseburia and Barnesiella could moderately predict dietary variety status. CONCLUSION: Higher DVS was correlated with higher microbial diversity and more abundance of some potentially beneficial bacteria but with less some potentially pathogenic bacteria. A high variety dietary, therefore, should be recommended in our daily life.

Peony seed oil decreases plasma cholesterol and favorably modulates gut microbiota in hypercholesterolemic hamsters.

PURPOSE: Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. METHODS: Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6 weeks. RESULTS: PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. CONCLUSIONS: It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.

Cholesterol-lowering activity of protocatechuic acid is mediated by increasing the excretion of bile acids and modulating gut microbiota and producing short-chain fatty acids.

The present study aimed to investigate the effects of protocatechuic acid (PCA) on plasma lipid profiles and associated mechanisms with a focus on reshaping gut microbiota. Twenty-four male hamsters were randomly divided into three groups receiving a high-cholesterol diet (HCD) and two HCD diets containing 0.5% (PL) and 1% (PH) PCA, respectively. Feeding PL and PH diets for six weeks significantly reduced plasma total cholesterol by 18% and 24%, respectively. PL and PH diets also significantly lowered plasma non-HDL cholesterol by 37% and 44%, respectively. This was accompanied by an increase in fecal short-chain fatty acids (SCFAs) and fecal bile acids with up-regulation on gene of cholesterol 7α-hydroxylase and down-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase in the liver. Dietary PCA supplementation decreased hepatic lipid accumulation, whereas it increased fecal excretion of lipids. The 16S rRNA analysis found that dietary PCA significantly reduced the ratio of Firmicutes to Bacteroidetes and increased the relative abundance of Bacteroidales S24-7, whereas it reduced the abundance of Lactobacillaceae. It was concluded that dietary PCA favorably modulated plasma lipid profiles and prevented the accumulation of hepatic cholesterol and lipid disposition. Such effect was mediated at least partially by increasing gut production of SCFAs and fecal excretion of bile acids via modulating the gut microbiome.

Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration.

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

Blueberry and cranberry anthocyanin extracts reduce bodyweight and modulate gut microbiota in C57BL/6 J mice fed with a high-fat diet.

PURPOSE: Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota. METHODS: C57BL/6 J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively. RESULTS: Feeding BL and BH diets significantly decreased body weight gain by 20-23%, total adipose tissue weight by 18-20%, and total liver lipids by 16-18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha (TNF-α) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA). CONCLUSIONS: It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice.

Hawthorn fruit extract reduced trimethylamine-N-oxide (TMAO)-exacerbated atherogenesis in mice via anti-inflammation and anti-oxidation.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. METHODS: Five groups of male Apolipoprotein E knock-out (ApoE-/-) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. RESULTS: Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. CONCLUSIONS: The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice.

Ursolic acid alleviates hypercholesterolemia and modulates the gut microbiota in hamsters.

Ursolic acid (UA) is a triterpenoid acid widely abundant in fruits and vegetables such as apple, blueberry and cranberry. The present study was carried out to investigate the effect of UA supplementation in diet on blood cholesterol, intestinal cholesterol absorption and gut microbiota in hypercholesterolemic hamsters. A total of thirty-two hamsters were randomly assigned to four groups and given a non-cholesterol diet (NCD), a high-cholesterol diet containing 0.1% cholesterol (HCD), an HCD diet containing 0.2% UA (UAL), or an HCD diet containing 0.4% UA (UAH) for 6 weeks. Results showed that UA supplementation reduced plasma cholesterol by 15-16% and inhibited intestinal cholesterol absorption by 2.6-9.2%. The in vitro micellar cholesterol solubility experiment clearly demonstrated that UA could displace 40% cholesterol from micelles. In addition, UA decreased the ratio of Firmicutes to Bacteroidetes, whereas it enhanced the growth of short chain fatty acid (SCFA)-producing bacteria in the intestine. In conclusion, UA possessed a cholesterol-lowering activity and could favorably modulate the gut microbiota.