Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.

BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.

Mapping multi-omics characteristics related to short-term PM2.5 trajectory and their impact on type 2 diabetes in middle-aged and elderly adults in Southern China.

The relationship between PM2.5 and metabolic diseases, including type 2 diabetes (T2D), has become increasingly prominent, but the molecular mechanism needs to be further clarified. To help understand the mechanistic association between PM2.5 exposure and human health, we investigated short-term PM2.5 exposure trajectory-related multi-omics characteristics from stool metagenome and metabolome and serum proteome and metabolome in a cohort of 3267 participants (age: 64.4 ± 5.8 years) living in Southern China. And then integrate these features to examine their relationship with T2D. We observed significant differences in overall structure in each omics and 193 individual biomarkers between the high- and low-PM2.5 groups. PM2.5-related features included the disturbance of microbes (carbohydrate metabolism-associated Bacteroides thetaiotaomicron), gut metabolites of amino acids and carbohydrates, serum biomarkers related to lipid metabolism and reducing n-3 fatty acids. The patterns of overall network relationships among the biomarkers differed between T2D and normal participants. The subnetwork membership centered on the hub nodes (fecal rhamnose and glycylproline, serum hippuric acid, and protein TB182) related to high-PM2.5, which well predicted higher T2D prevalence and incidence and a higher level of fasting blood glucose, HbA1C, insulin, and HOMA-IR. Our findings underline crucial PM2.5-related multi-omics biomarkers linking PM2.5 exposure and T2D in humans.

Proteome-wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis: A 9.8-year prospective study.

The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)-related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta-analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.

Comparing a new multimorbidity index with other multimorbidity measures for predicting disability trajectories.

BACKGROUND: The optimal multimorbidity measures for predicting disability trajectories are not universally agreed upon. We developed a multimorbidity index among middle-aged and older community-dwelling Chinese adults and compare its predictive ability of disability trajectories with other multimorbidity measures. METHODS: This study included 17,649 participants aged ≥50 years from the China Health and Retirement Longitudinal Survey 2011-2018. Two disability trajectory groups were estimated using the total disability score differences calculated between each follow-up visit and baseline. A weighted index was constructed using logistic regression models for disability trajectories based on the training set (70 %). The index and the condition count were used, along with the pattern identified by the latent class analysis to measure multimorbidity at baseline. Logistic regression models were used in the training set to examine associations between each multimorbidity measure and disability trajectories. C-statistics, integrated discrimination improvements, and net reclassification indices were applied to compare the performance of different multimorbidity measures in predicting disability trajectories in the testing set (30 %). RESULTS: In the newly developed multimorbidity index, the weights of the chronic conditions varied from 1.04 to 2.55. The multimorbidity index had a higher predictive performance than the condition count. The condition count performed better than the multimorbidity pattern in predicting disability trajectories. LIMITATION: Self-reported chronic conditions. CONCLUSIONS: The multimorbidity index may be considered an ideal measurement in predicting disability trajectories among middle-aged and older community-dwelling Chinese adults. The condition count is also suggested due to its simplicity and superior predictive performance.

Early-life exposure to the Great Chinese Famine and gut microbiome disruption across adulthood for type 2 diabetes: three population-based cohort studies.

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.

Effectiveness and safety of interspinous spacer versus decompressive surgery for lumbar spinal stenosis: A meta-analysis of randomized controlled trials.

STUDY DESIGN: A meta-analysis of randomized controlled trials. OBJECTIVE: Our meta-analysis was conducted to investigate whether interspinous spacer (IS) results in better performance for patients with lumbar spinal stenosis (LSS) when compared with decompressive surgery (DS). BACKGROUND DATA: DS and IS are common surgeries for the treatment of LSS. However, controversy remains as to whether the IS is superior to DS. METHODS: We comprehensively searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for prospective randomized controlled trials that compared IS versus DS for LSS. The retrieved results were last updated on July 30, 2023. RESULTS: Eight studies involving 852 individuals were included in the meta-analysis. The pooled data indicated that IS was superior to DS considering shorter operation time (P = .003), lower dural violation rate (P = .002), better Zurich Claudication Questionnaire Physical function score (P = .03), and smaller foraminal height decrease (P = .004), but inferior to DS considering the higher rate of reoperation (P < .0001). There was no significant difference between the 2 groups regarding hospital stay (P = .26), blood loss (P = .23), spinous process fracture (P = .09), disc height decrease (P = .87), VAS leg pain score (P = .43), VAS back pain score (P = .26), Oswestry Disability Index score (P = .08), and Zurich Claudication Questionnaire symptom severity (P = .50). CONCLUSIONS: In summary, we considered that IS had similar effects with DS in hospital stay, blood loss, spinous process fracture, disc height decrease, VAS score, Oswestry Disability Index score, and Zurich Claudication Questionnaire Symptom severity, and was better in some indices such as operation time, dural violation, Zurich Claudication Questionnaire Physical function, and foraminal height decrease than DS. However, due to the higher rate of reoperation in the IS group, we considered that both IS and DS were acceptable strategies for treating LSS. As a novel technique, further well-designed studies with longer-term follow-up are needed to evaluate the effectiveness and safety of IS.

Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-Based Multi-Omics Study.

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Bioinspired and self-restorable alginate-tyramine hydrogels with plasma reinforcement for arthritis treatment.

Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.

Population serum proteomics uncovers a prognostic protein classifier for metabolic syndrome.

Metabolic syndrome (MetS) is a complex metabolic disorder with a global prevalence of 20%-25%. Early identification and intervention would help minimize the global burden on healthcare systems. Here, we measured over 400 proteins from ∼20,000 proteomes using data-independent acquisition mass spectrometry for 7,890 serum samples from a longitudinal cohort of 3,840 participants with two follow-up time points over 10 years. We then built a machine-learning model for predicting the risk of developing MetS within 10 years. Our model, composed of 11 proteins and the age of the individuals, achieved an area under the curve of 0.774 in the validation cohort (n = 242). Using linear mixed models, we found that apolipoproteins, immune-related proteins, and coagulation-related proteins best correlated with MetS development. This population-scale proteomics study broadens our understanding of MetS and may guide the development of prevention and targeted therapies for MetS.

Furan fatty acid metabolite CMPF is associated with lower risk of type 2 diabetes, but not chronic kidney disease: a longitudinal population-based cohort study.

BACKGROUND: Furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. OBJECTIVE: We performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. METHODS: In the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. RESULTS: Each standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). CONCLUSIONS: Our findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.

Predicting new-onset post-stroke depression from real-world data using machine learning algorithm.

Introduction: Post-stroke depression (PSD) is a serious mental disorder after ischemic stroke. Early detection is important for clinical practice. This research aims to develop machine learning models to predict new-onset PSD using real-world data. Methods: We collected data for ischemic stroke patients from multiple medical institutions in Taiwan between 2001 and 2019. We developed models from 61,460 patients and used 15,366 independent patients to test the models' performance by evaluating their specificities and sensitivities. The predicted targets were whether PSD occurred at 30, 90, 180, and 365 days post-stroke. We ranked the important clinical features in these models. Results: In the study's database sample, 1.3% of patients were diagnosed with PSD. The average specificity and sensitivity of these four models were 0.83-0.91 and 0.30-0.48, respectively. Ten features were listed as important features related to PSD at different time points, namely old age, high height, low weight post-stroke, higher diastolic blood pressure after stroke, no pre-stroke hypertension but post-stroke hypertension (new-onset hypertension), post-stroke sleep-wake disorders, post-stroke anxiety disorders, post-stroke hemiplegia, and lower blood urea nitrogen during stroke. Discussion: Machine learning models can provide as potential predictive tools for PSD and important factors are identified to alert clinicians for early detection of depression in high-risk stroke patients.

The Association between Circulating 25-Hydroxyvitamin D and Carotid Intima-Media Thickness Is Mediated by Gut Microbiota and Fecal and Serum Metabolites in Adults.

SCOPE: Vitamin D is vital to cardiovascular health. This study examines the association between plasma 25-hydroxyvitamin D (25[OH]D) and the progression of carotid intima-media thickness (cIMT) and identifies the potential mediating biomarkers of gut microbiota and metabolites in adults. METHODS AND RESULTS: This 9-year prospective study includes 2975 subjects with plasma 25(OH)D at baseline and determined cIMT every 3 years. Higher circulating 25(OH)D is associated with decreased odds of higher (≥median) 9-year cIMT changes at the common carotid artery (hΔCCA-cIMT) (p-trend < 0.001). Multivariable-adjusted OR (95%CI) of hΔCCA-cIMT for tertiles 2 and 3 (vs. 1) of 25(OH)D is 0.87 (0.73-1.04) and 0.68 (0.57-0.82). Gut microbiome and metabolome analysis identify 18 biomarkers significantly associated with both 25(OH)D and hΔCCA-cIMT, including three microbial genera, seven fecal metabolites, eight serum metabolites, and pathway of synthesis and degradation of ketone bodies. Mediation/path analyses show the scores generated from the overlapped differential gut microbiota, fecal and serum metabolites, and serum acetoacetic acid alone could mediate the beneficial association between 25(OH)D and hΔCCA-cIMT by 10.8%, 23.1%, 59.2%, and 62.0% (all p < 0.05), respectively. CONCLUSIONS: These findings show a beneficial association between plasma 25(OH)D and the CCA-cIMT progression. The identified multi-omics biomarkers provide novel mechanistic insights for the epidemiological association.

Associations of serum betaine with blood pressure and hypertension incidence in middle-aged and older adults: a prospective cohort study.

The impact of betaine on the development of hypertension remains unclear, and prospective data are sparse. We aimed to investigate the association of serum betaine with repeated measurements of blood pressure (BP) and hypertension incidence. This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. Baseline serum betaine was measured by high-performance liquid chromatography-tandem mass spectrometry. BP and hypertension status were assessed at the baseline and 3-year intervals. Linear mixed-effects models (LMEMs) were used to analyze the longitudinal association of serum betaine with BP (n = 1996). Cox proportional hazard models were used to evaluate the association of baseline serum betaine with hypertension incidence (n = 1339). LMEMs showed that compared with the lowest quartile group, the higher quartile groups had lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (all P-trend < 0.05). Each standard deviation (16.3 µmol L-1) increase in serum betaine was associated with -0.92 (-1.52, -0.32) mmHg of SBP, -0.49 (-0.84, -0.13) mmHg of DBP and -0.43 (-0.81, -0.05) mmHg of pulse pressure. During a median follow-up of 9.2 years, 371 incident cases of hypertension were identified. Serum betaine was associated with lower risk of hypertension only when comparing the third quartile level with the lowest quartile (HR, 0.74; 95% CI, 0.56-0.99). A nonlinear association between serum betaine and the risk of hypertension was found (P-nonlinear = 0.040). A higher serum betaine level was associated with lower risk of hypertension below 54.5 µmol L-1. Our findings suggested that higher serum betaine was associated with favorable blood pressure in middle-aged and older Chinese adults. Higher concentrations of serum betaine were related to lower hypertension risk in people with relatively low serum betaine concentrations.

Influence of Cross-Linking and Crystalline Morphology on the Shape-Memory Properties of PET/PEN/PCL Copolyesters Using Trimesic Acid and Glycerol.

PCL-based biodegradable shape-memory polymers (SMPs) are limited in strength, which restricts their practical applications. In this study, a series of novel SMPs, composed of poly(ethylene terephthalate) (PET), poly(ethylene naphthalate) (PEN), and poly(ε-caprolactone) (PCL), were synthesized and cross-linked using planar (benzene-1,3,5-tricarboxylic acid, BTC) or non-planar (glycerol, GC) cross-linkers via the one-pot method. The influence of different kinds of cross-linkers and hard segments of copolyesters on the thermal properties, crystallization behavior, mechanical properties, shape-memory performance, and degradability was investigated by FT-IR, 1H-NMR, DSC, DMA, TGA, XRD, tensile test, intrinsic viscosity measurement, and in vitro enzymatic degradation test. The results indicate that the tensile strength of the copolyester can be significantly improved from 27.8 to 53.2 MPa by partially replacing PET with PEN while maintaining its shape-memory characteristics. Moreover, a small amount of cross-linking modification leads to higher temperature sensitivity, improved shape recovery rate at third round (Rr(3) = 99.1%), and biodegradability in the cross-linked PET/PEN/PCL shape-memory polymers. By changing the crystallization morphology and cross-linking forms of the material, we have developed a shape-memory polymer with both high strength and a high shape recovery rate, which provides a new strategy for the development of shape-memory materials.

The gut microbiota-bile acid axis mediates the beneficial associations between plasma vitamin D and metabolic syndrome in Chinese adults: A prospective study.

BACKGROUND & AIMS: Previous studies have suggested that circulating 25-hydroxyvitamin D (25 [OH]D, VD) and the gut microbiota-bile acid axis play crucial roles in metabolic health. Exploring the mediating role of the gut microbiota-bile acid axis would improve our understanding of the mechanisms underlying the effects of VD on human metabolic health. This study examined the association between plasma 25(OH)D and the prevalence/incidence of metabolic syndrome (MetS) and the mediating role of the gut microbiota-bile acid axis. METHODS: This prospective study included 3180 participants with plasma 25(OH)D data at baseline and 2966 participants with a 9-year follow-up. MetS was determined every three years. The gut microbiota was analyzed by 16S rRNA sequencing in 1752 participants, and targeted bile acid metabolites in feces were further determined in 974 participants using UPLC‒MS/MS at the middle of the study. Mediating roles of microbiota and bile acids in the VD-MetS associations were analyzed using mediation/path analyses adjusted for potential confounders. RESULTS: Among the 2966 participants who were followed-up, 1520, 193, 647, and 606 were MetS-free (normal), recovered, had incident MetS, and had persistent MetS, respectively. The multivariable-adjusted ORs (95% CIs) of MetS prevalence were 0.65 (0.50, 0.84) for baseline MetS and 0.46 (0.33, 0.65) for 9-year persistent MetS in quartile 4 (compared to quartile 1) of plasma 25(OH)D (median: 37.7 vs. 19.6, ng/ml). The corresponding HR (95% CI) of 9-year MetS incidence was 0.71 (0.56, 0.90) (all P-trend < 0.05). Higher VD concentrations were associated with greater α-diversity of the gut microbiota, which was inversely correlated with MetS risk. The groups classified by VD and MetS status had significantly different ß-diversity. Ruminiclostridium-6 and Christensenellaceae R-7 group were enriched in the high-VD group and were inversely associated with MetS. However, opposite associations were observed for Lachnoclostridium and Acidaminococcus. The overlapping differential microbial score (ODMS) developed from the four differential genera explained 12.2% of the VD-MetS associations (Pmediation = 0.015). Furthermore, the fecal bile acid score created from 11 differential bile acids related to ODMS and MetS mediated 34.2% of the association between ODMS and MetS (Pmediation = 0.029). Path analyses showed that the inverse association between plasma 25(OH)D and MetS could be mediated by the gut microbiota-bile acid axis. CONCLUSIONS: The findings suggest that the gut microbiota-bile acid axis partially mediates the beneficial association between plasma 25(OH)D and the risk of persistent MetS and incident MetS in the Chinese population.

Formula Milk Supplementation and Bone Acquisition in 4-6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

Increased Dietary Intakes of Total Protein, Animal Protein and White Meat Protein Were Associated with Reduced Bone Loss-A Prospective Analysis Based on Guangzhou Health and Nutrition Cohort, South China.

In this study, we aimed to prospectively investigate the relationships between different types of dietary protein and changes in bone mass in Chinese middle-aged and elderly people. Dietary intakes were evaluated by means of a validated food frequency questionnaire. Bone mineral density (BMD) was measured using a dual-energy bone densitometer at multiple bone sites. Multivariable regression models were applied to investigate the associations of the participants' dietary intakes of total protein, intakes of protein from various sources, and amino acid intakes with the annualized changes in BMD during a 3-year follow-up. A total of 1987 participants aged 60.3 ± 4.9 years were included in the analyses. Multivariable linear regression results showed that dietary intakes of total protein, animal protein, and protein from white meat were positively correlated with BMD changes, with standardized coefficients (ß) of 0.104, 0.073, and 0.074 at the femur neck (p < 0.01) and 0.118, 0.067, and 0.067 at the trochanter (p < 0.01), respectively. With each increase of 0.1g·kg-1·d-1 in animal protein and white meat protein intakes, the BMD losses were reduced by 5.40 and 9.24 mg/cm2 at the femur neck (p < 0.05) and 1.11 and 1.84 mg/cm2 at the trochanter (p < 0.01), respectively. Our prospective data, obtained from Chinese adults, showed that dietary total and animal protein, especially protein from white meat, could significantly reduce bone loss at the femur neck and trochanter.

Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility.

Identification of protein quantitative trait loci (pQTL) helps understand the underlying mechanisms of diseases and discover promising targets for pharmacological intervention. For most important class of drug targets, genetic evidence needs to be generalizable to diverse populations. Given that the majority of the previous studies were conducted in European ancestry populations, little is known about the protein-associated genetic variants in East Asians. Based on data-independent acquisition mass spectrometry technique, we conduct genome-wide association analyses for 304 unique proteins in 2,958 Han Chinese participants. We identify 195 genetic variant-protein associations. Colocalization and Mendelian randomization analyses highlight 60 gene-protein-phenotype associations, 45 of which (75%) have not been prioritized in Europeans previously. Further cross-ancestry analyses uncover key proteins that contributed to the differences in the obesity-induced diabetes and coronary artery disease susceptibility. These findings provide novel druggable proteins as well as a unique resource for the trans-ancestry evaluation of protein-targeted drug discovery.

Comparison of fecal and blood metabolome reveals inconsistent associations of the gut microbiota with cardiometabolic diseases.

Blood metabolome is commonly used in human studies to explore the associations of gut microbiota-derived metabolites with cardiometabolic diseases. Here, in a cohort of 1007 middle-aged and elderly adults with matched fecal metagenomic (149 species and 214 pathways) and paired fecal and blood targeted metabolomics data (132 metabolites), we find disparate associations with taxonomic composition and microbial pathways when using fecal or blood metabolites. For example, we observe that fecal, but not blood butyric acid significantly associates with both gut microbiota and prevalent type 2 diabetes. These findings are replicated in an independent validation cohort involving 103 adults. Our results suggest that caution should be taken when inferring microbiome-cardiometabolic disease associations from either blood or fecal metabolome data.

Increased Serum Adipsin Correlates with MAFLD and Metabolic Risk Abnormalities.

Purpose: A panel of international experts proposed a new definition of fatty liver in 2020, namely metabolic dysfunction-associated fatty liver disease (MAFLD). As an adipokine, adipsin is closely related to metabolic-related diseases. In this study, we aimed to evaluate the relationship among MAFLD, serum adipsin, and metabolic risk abnormalities. Methods: Our study was a cross-sectional study based on the first follow-up of the Guangzhou Nutrition and Health Study (GNHS). A total of 908 patients with hepatic steatosis were involved in our study. Detailed data of patients were collected based upon questionnaire information, physical examination, and blood biochemical test. Results: Among the 908 patients, 789 patients were diagnosed with MAFLD. The levels of serum adipsin in the MAFLD group and non-MAFLD group were (3543.00 (3187.94-3972.50) ng/mL) and (3095.33 (2778.71-3354.77) ng/mL) (P < 0.001), respectively. After adjusting for potential confounders, adipsin levels were found to be associated with MAFLD. The OR was 3.46 (95% CI: 1.57-7.64) for adipsin when comparing subjects in the highest tertile with those in the lowest tertile. With the increase in the number of metabolic risk abnormalities, both the levels of serum adipsin and the proportion of moderate to severe fatty liver increased (all p-trend < 0.001). Conclusion: Increased serum adipsin correlates with MAFLD. Both adipsin levels as well as fatty liver severity increase with higher numbers of metabolic risk abnormalities.