Effects of Chinese heart-healthy diet on blood lipids, glucose, and estimated 10-y cardiovascular disease risk among Chinese adults: results on secondary outcomes of a randomized controlled trial.

BACKGROUND: Healthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown. METHODS: In this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population. RESULTS: Among 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (-0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (-1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (-0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results. CONCLUSIONS: The CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted. This trial was registered at clinicaltrials.gov as NCT03882645.

Effect of lard plus soybean oil on blood pressure and other cardiometabolic risk factors in healthy subjects: a randomized controlled-feeding trial.

Lard has been consumed by humans for thousands of years, but its consumption has declined substantially in the last few decades, because of negative publicity about the consumption of animal-derived saturated fats. Emerging evidence highlights that lard plus soybean oil (blend oil) could be more beneficial for body weight and liver function than the individual use of the two oils. This study aimed to evaluate the effects of blend oil on cardiometabolic risk factors in healthy subjects. This was a parallel, three-arm, randomized controlled-feeding trial. 334 healthy subjects (mean age: 33.1 years, 60% women) were randomized into three isoenergetic diet groups with three different edible oils (30 g day-1) (soybean oil, lard, and blend oil [50% lard and 50% soybean oil]) for 12 weeks. 245 (73.4%) participants completed the study. After the 12-week intervention, reductions in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were greater in the blend oil group than in the other two groups (P = 0.023 and 0.008 for the interaction between the diet group and time, respectively). Reductions of SBP and DBP in the blend oil group were more significant than those in the soybean oil group with P = 0.008 and P = 0.026 and the lard group with P < 0.001 and P < 0.001. Changes in SBP/DBP at 12 weeks were -6.0 (95% CI: -8.6 to -3.4)/0.8 (95% CI: -1.7 to 3.2) mmHg in the blend oil group, -3.3 (95% CI: -5.7 to -0.9)/1.5 (95% CI: -1.0 to 4.0) mmHg in the soybean oil group and -1.2 (95% CI: -3.7 to 1.4)/3.3 (95% CI: 0.9 to 5.8) mmHg in the lard group. Subgroup analyses showed that blend oil significantly decreased SBP and DBP compared with the other two groups in participants with BP ≥ 130/80 mmHg and body mass index ≥25. There were no significant differences in the changes in body weight, waist circumference, serum lipids, or glucose between groups. In conclusion, our findings suggest that blend oil (lard plus soybean oil) reduces BP compared with soybean oil and lard in healthy subjects.

Effect of Lard or Plus Soybean Oil on Markers of Liver Function in Healthy Subjects: A Randomized Controlled-Feeding Trial.

Humans have consumed lard for thousands of years, but in recent decades, it has become much less popular because it is regarded as saturated fat. Animal studies showed that lard plus soybean oil (blend oil) was more advantageous for liver health than using either oil alone. This study aims to assess the effects of blend oil on liver function markers in healthy subjects. The 345 healthy subjects were randomized into 3 isoenergetic diet groups with different edible oils (30 g/day) (soybean oil, lard, and blend oil (50% lard and 50% soybean oil)) for 12 weeks. The reductions in both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were greater in the blend oil group than in the two other groups (p = 0.001 and <0.001 for the interaction between diet group and time, respectively). The reductions in AST and ALT in the blend oil group were more significant compared with those in the soybean oil group (p < 0.001) or lard group (p < 0.001). There were no significant differences in the other liver function markers between the groups. Thus, blend oil was beneficial for liver function markers such as AST and ALT compared with soybean oil and lard alone, which might help prevent non-alcoholic fatty liver disease in the healthy population.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

Water Level Has Higher Influence on Soil Organic Carbon and Microbial Community in Poyang Lake Wetland Than Vegetation Type.

Although microorganisms play a key role in the carbon cycle of the Poyang Lake wetland, the relationship between soil microbial community structure and organic carbon characteristics is unknown. Herein, high-throughput sequencing technology was used to explore the effects of water level (low and high levels above the water table) and vegetation types (Persicaria hydropiper and Triarrhena lutarioriparia) on microbial community characteristics in the Poyang Lake wetland, and the relationships between soil microbial and organic carbon characteristics were revealed. The results showed that water level had a significant effect on organic carbon characteristics, and that soil total nitrogen, organic carbon, recombinant organic carbon, particle organic carbon, and microbial biomass carbon were higher at low levels above the water table. A positive correlation was noted between soil water content and organic carbon characteristics. Water level and vegetation type significantly affected soil bacterial and fungal diversity, with water level exerting a higher effect than vegetation type. The impacts of water level and vegetation type were higher on fungi than on bacteria. The bacterial diversity and evenness were significantly higher at high levels above the water table, whereas an opposite trend was noted among fungi. The bacterial and fungal richness in T. lutarioriparia community soil was higher than that in P. hydropiper community soil. Although both water level and vegetation type had significant effects on bacterial and fungal community structures, the water level had a higher impact than vegetation type. The bacterial and fungal community changes were the opposite at different water levels but remained the same in different vegetation soils. The organic carbon characteristics of wetland soil were negatively correlated with bacterial diversity but positively correlated with fungal diversity. Soil water content, soluble organic carbon, C/N, and microbial biomass carbon were the key soil factors affecting the wetland microbial community. Acidobacteria, Alphaproteobacteria, Verrucomicrobia, Gammaproteobacteria, and Eurotiomycetes were the key microbiota affecting the soil carbon cycle in the Poyang Lake wetland. Thus, water and carbon sources were the limiting factors for bacteria and fungi in wetlands with low soil water content (30%). Hence, the results provided a theoretical basis for understanding the microbial-driven mechanism of the wetland carbon cycle.

Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model.

Sepsis is considered as a life-threatening organ dysfunction caused by a dysregulated response of the host to an infection. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition, and is the type of organ injury that is most commonly induced by sepsis. Resveratrol (RSV) has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties. The present study aimed to investigate whether RSV could mitigate sepsis-induced ALI/ARDS, and also to unravel the underlying mechanism. The model of sepsis was established by applying the cecal ligation and puncture (CLP) method, and mitochondria from the lung tissue were isolated to assess mitochondrial function, as determined from measuring mitochondrial superoxide production using MitoSOX red mitochondrial superoxide indicator and the membrane potential. It was found that RSV could exert a protective role in CLP-induced ALI/ARDS, as evidenced by moderate levels of inflammatory cell infiltration and interstitial edema, as well as decreased levels of C-reactive protein (P<0.01), interleukin (IL)-6 (P<0.01), IL-1ß (P<0.01) and tumor necrosis factor-α (P<0.01). Moreover, phospholipid scramblase 3 (PLSCR-3)-mediated mitochondrial dysfunction and mitophagy were shown to contribute towards the CLP-caused lung damage, which was reversed upon RSV administration, as demonstrated by improved mitochondrial function and markedly reduced increases in the protein levels of autophagy related (ATG)5 (P<0.01), ATG7 (P<0.05) and microtubule-associated protein 1A/1B-light chain 3 (LC3-Ⅰ/Ⅱ) (P<0.01), and a significantly increased expression of P62 (P<0.05). In addition, with regard to the CLP-induced lung injury in the mouse model, overexpression of PLSCR-3 was found to remove the beneficial effects observed upon RSV treatment. Taken together, the results of the present study have uncovered a novel molecular mechanism through which RSV may alleviate ALI/ARDS via regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in CLP-induced mouse model.

The alleviating effect of sphingosine kinases 2 inhibitor K145 on nonalcoholic fatty liver.

Sphingosine kinase 2 (SphK2) inhibitors are developed for tumor therapy as considering its anti-tumor effect. Many studies also explored SphK2 modulated glucose and lipid homeostasis, which extended its potential function for metabolic diseases therapy. In this study, we discovered a significant reduction of hepatic lipid accumulation as well as recovery of liver function in ob/ob mice with intraperitoneal injection of K145. Also, db/db mice received K145 showed improvement of both NALFD and hyperglycemia. We furtherly analyzed the genes associated with lipid metabolism and found a remarkable decreased expression of lipogenic genes including FAS, ACC1 and SREBP1c whereas elevated mitochondrial fatty acid ß-oxidation (FAO) related genes expression including CPT1A, MCAD, LCAD, PPAR-α, UCP2. Consistent to in vivo study, in vitro study also confirmed the role of K145 in decreasing lipid accumulation in human HL7702 cells, while inhibiting FAS, ACC1 and SREBP1c mRNA expression. It indicated a possible mechanism of K145 induced improvement of hepatic lipid accumulation partly via inhibition of lipigenesis. Our study suggested a promising role of K145 in drug development for NAFLD and diabetes therapy.

Dexmedetomidine protects the heart against ischemia reperfusion injury via regulation of the bradykinin receptors.

BACKGROUND: Dexmedetomidine (DEX) has been reported to protect the heart against ischemia reperfusion (I/R) injury. However, the exact mechanisms are still not fully understood. METHODS AND RESULTS: A rat cardiac I/R injury model was induced by ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion for 2 h, and DEX was administered intravenously 30 min before ischemia. We confirmed that DEX treatment mitigated cardiac I/R injury. Interestingly, we found that DEX regulated the expression of bradykinin (BK) receptors (B1R and B2R) in rat hearts during I/R injury and enhanced the protective action of BK administered during reperfusion. Moreover, in vitro hypoxia reoxygenation (H/R) injury was induced in neonatal rat cardiomyocytes (CMs), and DEX was administered 1 h before hypoxia. The in vitro findings were consistent with the in vivo experiments. We found that an α2-adrenoceptor (α2-AR) antagonist (yohimbine) completely aborted DEX-induced B1R and B2R regulation; an adenylyl cyclase (AC) agonist (forskolin) blocked B1R downregulation, while a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) blocked B2R upregulation. The above findings indicated that DEX interacted with α2-AR in cardiomyocytes, inhibited B1R expression via suppression of AC, and stimulated B2R expression via activation of PI3K. CONCLUSIONS: DEX regulates BK receptor expression and potentiates the protection of BK in cardiac I/R injury, which suggests that modulating endogenous cardioprotective factors may play an important role in DEX-induced cardioprotection.

Inhibition of lipogenesis and induction of apoptosis by valproic acid in prostate cancer cells via the C/EBPα/SREBP-1 pathway.

Lipid metabolism reprogramming is now accepted as a new hallmark of cancer. Hence, targeting the lipogenesis pathway may be a potential avenue for cancer treatment. Valproic acid (VPA) emerges as a promising drug for cancer therapy; however, the underlying mechanisms are not yet fully understood. In this study, we aimed to investigate the effects and mechanisms of VPA on cell viability, lipogenesis, and apoptosis in human prostate cancer PC-3 and LNCaP cells. The results showed that VPA significantly reduced lipid accumulation and induced apoptosis of PC-3 and LNCaP cells. Moreover, the expression of CCAAT/enhancer-binding protein α (C/EBPα), as well as sterol regulatory element-binding protein 1 (SREBP-1) and its downstream effectors, including fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and anti-apoptotic B-cell lymphoma 2 (Bcl-2), was markedly decreased in PC-3 and LNCaP cells after VPA administration. Mechanistically, the overexpression of C/EBPα rescued the levels of SREBP-1, FASN, ACC1, and Bcl-2, enhanced lipid accumulation, and attenuated apoptosis of VPA-treated PC-3 cells. Conversely, knockdown of C/EBPα by siRNA further decreased lipid accumulation, enhanced apoptosis, and reduced the levels of SREBP-1, FASN, ACC1, and Bcl-2. In addition, SREBP-1a and 1c enhanced the expressions of FASN and ACC1, but only SREBP-1a had a significant effect on Bcl-2 expression in VPA-treated PC-3 cells. Based on the results, we concluded that VPA significantly inhibits cell viability via decreasing lipogenesis and inducing apoptosis via the C/EBPα/SREBP-1 pathway in prostate cancer cells. Therefore, VPA that targets lipid metabolism and apoptosis is a promising candidate for PCa chemotherapy.

Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes.

AIMS: Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. MATERIALS AND METHODS: One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-ß, early-phase insulin secretion index InsAUC30/GluAUC30, and total-phase insulin secretion index InsAUC120/GluAUC120. RESULTS: Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-ß level, early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. CONCLUSION: SIBO may be involved in lower levels of insulin release and worse glycemic control.

Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice.

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

The Compensatory Tillering in the Forage Grass Hordeum brevisubulatum After Simulated Grazing of Different Severity.

The response of compensatory growth is an important adaptive strategy for plants to grazing. However, most previous studies on compensatory growth of plants focused on the compensation of the biomass or the number of sexual reproductive offspring and neglected the compensatory growth of vegetative reproduction (VR). This is important not only for plant compensatory growth studies, but also for theoretical and practical studies of grassland production. The clonal tussock grass Hordeum brevisubulatum was selected as the research object. Four different clipping severities (unclipping and clipping stubble at heights of 15, 10, and 5 cm) at the jointing stage and flowering stage were implemented to study the effect of simulated grazing. To explore the effect of recovery growth time on plant growth after simulated grazing, three sampling times were used at different recovery times after simulated grazing (1, 3, and 7 weeks). We found that light and moderate grazing severity significantly increased the number of vegetative reproduction modules, the promotion of simulated grazing on the number of vegetative reproduction modules was higher in the jointing stage than the flowering stage, and the increase in simulated grazing severity decreased with prolonged recovery growth time. The number of tillers significantly decreased with the increase in simulated grazing in both the jointing and flowering stages at 1 week after damage, and the decreasing effect weakened with the prolonged recovery growth time. The bud number mainly showed over-compensation, the juvenile tiller number showed complete compensation, and the tiller number showed under-compensation at 1 and 3 weeks after recovery growth. The number of tillers showed complete compensation under different grazing severities in the jointing stage, while it showed under-compensation in the flowering stage at 7 weeks after recovery growth. Our results indicated that different grazing severities in the jointing stage could promote the output of tillers with matter production capacity from vegetative reproduction modules, as well as improve the capability of compensatory growth. Therefore, in plant production, there will be a sustainable development effect on the renewal and productivity of the H. brevisubulatum population, resulting in different grazing severities in the jointing stage.

Human milk microbiota development during lactation and its relation to maternal geographic location and gestational hypertensive status.

Bacteria in human milk could directly seed the infant intestinal microbiota, while information about how milk microbiota develops during lactation and how geographic location, gestational hypertensive status, and maternal age influence this process is limited. Here, we collected human milk samples from mothers of term infants at the first day, 2 weeks, and 6 weeks postpartum from 117 longitudinally followed-up mothers (age: 28.7 ± 3.6 y) recruited from three cities in China. We found that milk microbial diversity and richness were the highest in colostrum but gradually decreased over lactation. Microbial composition changed across lactation and exhibited more discrete compositional patterns in 2-week and 6-week milk samples compared with colostrum samples. At phylum level, the abundance of Proteobacteria increased during lactation, while Firmicutes showed the opposite trend. At genus level, Staphylococcus, Streptococcus, Acinetobacter, Pseudomonas, and Lactobacillus were predominant in colostrum samples and showed distinct variations across lactation. Maternal geographic location was significantly associated with the milk microbiota development and the abundance of predominant genus. In addition, milk from mothers with gestational prehypertension had a different and less diverse microbial community at genus level in early lactation times, and contained less Lactobacillus in the 2-week milk samples than those from normotensive mothers. Findings of our study outlined the human milk microbial diversity and community development over lactation, and underscored the importance of maternal geographic locations and gestational hypertensive status on milk microbiota, which might have important implications in the establishment of the infant intestinal microbiota via breastfeeding.

Salvianolic acid B improved insulin resistance through suppression of hepatic ER stress in ob/ob mice.

Impaired insulin sensitivity of insulin-sensitive tissues plays a major role in the pathogenesis of type 2 diabetes, salvianolic acid B (SalB), a natural antioxidant usually treated various cardiovascular diseases was also reported potential utility on diabetes and dyslipidemia. Based on these, we aimed to explored whether the antioxidant effect of SalB play a pivotal role in the molecular mechanisms leading to insulin resistance. We found that SalB improved glucose tolerance and insulin sensitivity, decreased serum ALT, AST and ALP levels of ob/ob mice. Also, transcription of Bip and CHOP, phosphorylation of PERK and IRE1 for endoplasmic reticulum stress (ER) and phosphorylation of IRS-1 for insulin sensitivity in the liver of ob/ob mice were relieved by SalB. Further, SalB decreased phosphorylation of PERK, IRE1 and IRS1 and transcription of Bip and CHOP stimulated by palmitate of hepatic cells HL7702, but did not reversed phosphorylation of JNK and IRS1 and transcription of Bip and CHOP when ER stress was stimulated by tunicamycin. These data shows that SalB improved insulin resistance of ob/ob mice through suppression of hepatic ER stress.

Overweight and underweight status are linked to specific gut microbiota and intestinal tricarboxylic acid cycle intermediates.

BACKGROUND & AIMS: Intestinal short-chain fatty acids have been demonstrated to modulate host energy metabolism and are elevated in overweight and obese individuals. We hypothesized that other intestinal energy products especially tricarboxylic acid (TCA) cycle intermediates might also related to overweight status. In addition, little information is available regarding to the potential relationship between gut microbiota and underweight status. Therefore, the aim of this study was to investigate whether gut microbiota and intestinal energy metabolites differ in underweight, normal weight, and overweight individuals, and their correlations with host cardiometabolic risk factors. SUBJECTS/METHODS: Gut microbiome, intestinal energy metabolites, circulating cardiometabolic risk factors, and proinflammatory markers were determined in 29 underweight, 67 normal weight, and 67 overweight adults. RESULTS: The fecal concentrations of succinic acid, fumaric acid, malic acid, propionic acid, and adipic acid were significantly increased in the overweight individuals in parallel with a higher relative abundance of Veillonellacea after adjusting for multiple comparisons (all p < 0.05). The intestinal concentration of TCA cycle intermediate succinic acid was positively associated with body weight (r = 0.28, p = 0.04), and malic acid were in positive association with circulating total cholesterol, low-density lipoprotein cholesterol, and interleukin-1ß (all r > 0.25, p < 0.05). Compared with the normal weight individuals, the gut microbial α-diversity was lower in the overweight (p = 0.007 for Shannon index and p = 0.009 for Ace index) and underweight (p = 0.05 for Shannon index and p = 0.08 for Ace index) groups. However, no significant differences in the overall gut microbiota composition were observed among the three groups. CONCLUSIONS: Our findings revealed that low gut microbiota diversity was associated with both overweight and underweight status. Intestinal TCA cycle intermediates were associated with overweight development and might be potential markers for future studies related to gut microbiota and host cardiometabolic health.

Contribution of diet to gut microbiota and related host cardiometabolic health: diet-gut interaction in human health.

Obesity and cardiometabolic diseases in both developed and developing counties in a state of nutrition transition are often related to diet, which also play a major role in shaping human gut microbiota. The human gut harbors diverse microbes that play an essential role in the well-being of their host. Complex interactions between diet and microorganisms may lead to beneficial or detrimental outcomes to host cardiometabolic health. Despite numerous studies using rodent models indicated that high-fat diet may disrupt protective functions of the intestinal barrier and contribute to inflammatory processes, evidence from population-based study is still limited. In our recent study of a 6-month randomized controlled-feeding trial, we showed that high-fat, low-carbohydrate diet was associated with unfavorable changes in gut microbiota, fecal microbial metabolites, and plasma proinflammatory factors in healthy young adults. Here, we provide an overview and extended discussion of our key findings, and outline important future directions.

Unconjugated and secondary bile acid profiles in response to higher-fat, lower-carbohydrate diet and associated with related gut microbiota: A 6-month randomized controlled-feeding trial.

BACKGROUND & AIMS: Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. METHODS: In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. RESULTS: The higher-fat diet resulted in an elevated concentration of total BAs (p < 0.001), and unconjugated BAs (p = 0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3ß-DCA and taurolithocholic acid (TLCA) (p < 0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r = 0.31, p = 0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r > 0.3, p = 0.02 and p = 0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p = 0.05). CONCLUSIONS: The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.

Habitual animal fat consumption in shaping gut microbiota and microbial metabolites.

Short-term intervention studies support a link between animal-based diet and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. However, whether habitual animal fat intake is associated with gut-related health remains unclear. Thus, we collected dietary information, clinical data and fecal samples from 297 healthy young subjects and characterized gut microbiota by 16S rRNA gene sequencing and microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs) using a gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF/MS) system and ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) platform, respectively. We found that the microbial diversity of butyric acid (rho = -0.17, p = 0.004 for the Shannon index) and the concentrations of butyric acid (rho = -0.33, p < 0.001) and valeric acid (rho = -0.28, p = 0.002) were negatively associated with animal fat consumption. In line with this, the abundance of SCFAs-producing bacteria such as Blautia, Eubacterium hallii, and Megamonas were significantly lower in the high animal fat group compared with the low animal fat group (all p < 0.05). Additionally, the high animal fat group had higher concentrations of total (p = 0.06) and unconjugated (p = 0.09) BAs relative to the lower animal fat groups. The findings of our study indicate that a diet with higher animal-based fat consumption is likely to be associated with moderately unfavorable impacts on gut microbial diversity, community, and regulation of fecal SCFAs, which may influence the host cardiometabolic health in the long term among healthy Chinese adults whose diet is in a nutrition transition.

Effects of Simulated Herbivory on the Vegetative Reproduction and Compensatory Growth of Hordeum brevisubulatum at Different Ontogenic Stages.

The response of plant vegetative reproduction and compensatory growth to herbivory has been widely discussed in biological and ecological research. Most previous research has supported the idea that both vegetative reproduction and compensatory growth are affected by their ontogenic stage. However, in many studies, the effects of foraging at different ontogenic stages was often confounded with the effects of foraging at different phenological periods for perennials. Our experiment was conducted in a natural meadow with a perennial grass, Hordeum brevisubulatum, and four ontogenic stages were chosen as our experimental objects. Three different clipping intensities during three phenological periods were implemented to explore the effects of simulating animal foraging on vegetative reproduction and compensatory plant growth. The results indicated that there were significant effects of ontogenic stage, phenological period, and clipping intensity on vegetative reproduction and compensatory growth. Moderate clipping intensities significantly increased the number of vegetative tillers, the total number of juvenile tillers and buds, and the aboveground biomass at early phenological periods for individuals at early ontogenic stages. Our results suggested that moderate clipping intensities could induce only an over-compensation response in perennial grasses at both the early ontogenic stage and phenological period, and the ability of compensatory growth gradually decreased with the progression of the ontogenic stage. This is of great significance to the primary production of grasslands subjected to herbivory.

Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial.

OBJECTIVE: To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS: In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS: The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION: Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER: NCT02355795; Results.