Gut microbiota accelerates obesity in peri-/post-menopausal women via Bacteroides fragilis and acetic acid.

OBJECTIVE: Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women. METHODS: We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods. RESULTS: Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels. CONCLUSIONS: We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.

Bioactive polysaccharides and their potential health benefits in reducing the risks of atherosclerosis: A review.

Atherosclerosis is a kind of lipid-driven chronic inflammatory disease of arteries and is the principal pathological basis of life-threatening cardiovascular disease events, such as strokes and heart attacks. Clinically, statins are the most commonly prescribed drugs for the treatment of atherosclerosis, but prolonged use of these drugs exhibit many adverse reactions and have limited efficacy. Polysaccharides are important natural biomacromolecules widely existing in plants, animals, microorganisms and algae. They have drawn considerable attention worldwide due to their multiple healthy functions, along with their non-toxic property. Importantly, a growing number of studies have demonstrated that bioactive polysaccharides exhibit prominent efficiency in controlling atherosclerotic risk factors like hyperlipemia, hypertension, oxidative stress, and inflammation. In recent decades, various bioactive polysaccharides with different structural features and anti-atherosclerotic potential from natural sources have been isolated, purified, and characterized. The aim of this review is to focus on the research progress of natural polysaccharides in reducing the risks of atherosclerosis based on evidence of in vitro and in vivo studies from 1966 to 2022. PRACTICAL APPLICATIONS: In the future, it is still necessary to strengthen the research on the development and mechanism of polysaccharides with anti-atherosclerotic potential. These anti-atherosclerotic polysaccharides with different structural characteristics and physiochemical properties from different sources will constitute a huge source of materials for future applications, especially in functional foods and drugs. The information summarized here may serve as useful reference materials for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

Polygonatum cyrtonema Hua polysaccharide exhibits anti-fatigue activity via regulating osteocalcin signaling.

In the present study, we explored the anti-fatigue activity and its potential mechanism of a purified Polygonatum cyrtonema polysaccharide (PCP) on mice using weight-loaded swimming test. Results showed that PCP remarkably prolonged the exhaustive swimming time of mice when compared with normal control group. Meanwhile, PCP decreased serum levels of lactic acid (LA), blood uric nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), and increased the contents of liver glycogen, muscle glycogen and muscle ATP. These results revealed that PCP had good anti-fatigue ability. The histomorphologic analysis showed that PCP increased the cross-section area of the muscle fibers. Furthermore, PCP significantly enhanced the protein levels of bone morphogenetic protein-2 (BMP-2), phosphor-Smad1, Runt-related transcription factor 2 (Runx2) and osteocalcin (OC) in skeleton. Similar variation was also observed in the expression of osteocalcin signaling mediators of phosphorylated cAMP-response element binding protein (p-CREB) and phosphorylated hormone-sensitive lipase (p-HSL) in skeletal muscle. These results suggested that PCP resisted fatigue possibly via regulating osteocalcin signaling.

Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women.

BACKGROUND: Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community-dwelling healthy menopausal women. METHODS: Estimated SMM was derived from whole-body dual-energy X-ray absorptiometry. We performed integrated analyses on whole-genome sequencing, shotgun metagenomic sequencing, and serum short-chain fatty acids (SCFAs), as well as available host SMM measurements among community-dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome-wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one-sample and two-sample Mendelian randomization (MR) analyses, respectively. RESULTS: In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate-producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10-7 ) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10-4 ) and B. virosa (SCC = 0.17, P = 2.4 × 10-4 )]. One-sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two-sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). CONCLUSIONS: Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.

The hydrogel of whey protein isolate coated by lotus root amylopectin enhance the stability and bioavailability of quercetin.

In this study, whey protein isolate (WPI)-quercetin (Que)-lotus root amylopectin (LRA) hydrogels (WPI-QUE-LRA) was developed to improve the solubility, stability and bioavailability of quercetin. Results showed that the favorable WPI-QUE-LRA was formed using WPI and LRA in the ratio of 1:2 at pH 7.0. Under this condition, the average size, polydispersity index, zeta potential of the WPI-QUE-LRA was 179.5 nm, 0.271, -18.6 mV, respectively. The analysis of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffractometer revealed that the quercetin was successfully encapsulated in WPI-LRA, giving a high encapsulation efficiency of 92.4 %. Moreover, the WPI-LRA could significantly improve the storage stability and photochemical stability of quercetin. The in vitro and in vivo experiments showed that LRA-coated WPI hydrogel can enable quercetin to be stable in stomach and be effectively released in small intestine, leading to the enhancement of the bioavailability of quercetin.

Sarcopenia-related traits and coronary artery disease: a bi-directional Mendelian randomization study.

Previous Mendelian randomization (MR) studies have yielded a conflicting causal relationship between sarcopenia and coronary artery disease (CAD), and lack the association of CAD with sarcopenia. We performed a bi-directional MR approach to clarify the causality and causal direction between sarcopenia-related traits and CAD. In stage 1 analysis, estimates of inverse variance weighting (IVW) and several sensitivity analyses were obtained by applying genetic variants that predict sarcopenia-related traits to CAD. Conversely, we also applied genetic variants that predict CAD to sarcopenia-related traits in stage 2 analyses. IVW analysis showed that higher handgrip strength reduces risk for CAD: A 1-kilogram (kg) increase in genetically determined left handgrip strength reduced odds of CAD by 36% [odds ratio (OR) = 0.64, 95% confidence interval (CI) 0.498 - 0.821, p = 4.56E-04], and right handgrip strength reduced odds of CAD by 41.1% (OR = 0.599, 95% CI 0.476 - 0.753, p = 1.10E-05). However, genetically predicted CAD did not show any causal association with handgrip strength, and no significant causal relationship was detected between genetically instrumented body lean mass and CAD. Our results suggest that decreased muscle strength but not decreased muscle mass leads to the increased risk of CAD in sarcopenia.

Causal Effects of Genetically Predicted Cardiovascular Risk Factors on Chronic Kidney Disease: A Two-Sample Mendelian Randomization Study.

Observational studies have demonstrated that cardiovascular risk factors are associated with chronic kidney disease (CKD). However, these observational associations are potentially influenced by the residual confounding, including some unmeasured lifestyle factors and interaction risk factors. Two-sample mendelian randomization analysis was conducted in this study to evaluate whether genetically predicted cardiovascular risk factors have a causal effect on the risk of CKD. We selected genetic variants associated with cardiovascular risk factors and extracted the corresponding effect sizes from the largest GWAS summary-level dataset of CKD. Cardiovascular risk factors contain high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglyceride (TG), glycated hemoglobin (HbA1c), fasting glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP). A Bonferroni corrected threshold of P = 0.006 was considered as significant, and 0.006 < P < 0.05 was considered suggestive of evidence for a potential association. Genetically predicted DBP was significantly associated with CKD [odds ratio (OR) was 1.35 (95% confidence interval (CI) (1.10, 1.65); P = 0.004)]. There was suggestive evidence for potential associations between genetically predicted higher HDL cholesterol [OR: 0.88, 95%CI (0.80, 0.98), P = 0.025] and lower adds of CKD, and between higher SBP [OR: 1.36, 95%CI (1.07, 1.73), P = 0.013] and higher adds of CKD. However, genetically predicted LDL cholesterol, TC, TG, HbA1c, and fasting glucose did not show any causal association with CKD.