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Genetically Determined Circulating Lactase/Phlorizin Hydrolase Concentrations and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.
Han, S, Yao, J, Yamazaki, H, Streicher, SA, Rao, J, Nianogo, RA, Zhang, Z, Huang, BZ
Nutrients. 2024;(6)
Abstract
Previous research has found that milk is associated with a decreased risk of colorectal cancer (CRC). However, it is unclear whether the milk digestion by the enzyme lactase-phlorizin hydrolase (LPH) plays a role in CRC susceptibility. Our study aims to investigate the direct causal relationship of CRC risk with LPH levels by applying a two-sample Mendelian Randomization (MR) strategy. Genetic instruments for LPH were derived from the Fenland Study, and CRC-associated summary statistics for these instruments were extracted from the FinnGen Study, PLCO Atlas Project, and Pan-UK Biobank. Primary MR analyses focused on a cis-variant (rs4988235) for LPH levels, with results integrated via meta-analysis. MR analyses using all variants were also undertaken. This analytical approach was further extended to assess CRC subtypes (colon and rectal). Meta-analysis across the three datasets illustrated an inverse association between genetically predicted LPH levels and CRC risk (OR: 0.92 [95% CI, 0.89-0.95]). Subtype analyses revealed associations of elevated LPH levels with reduced risks for both colon (OR: 0.92 [95% CI, 0.89-0.96]) and rectal cancer (OR: 0.92 [95% CI, 0.87, 0.98]). Consistency was observed across varied analytical methods and datasets. Further exploration is warranted to unveil the underlying mechanisms and validate LPH's potential role in CRC prevention.
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Association Between Circulating Zinc and Risk for Childhood Asthma and Wheezing: A Meta-analysis on 21 Articles and 2205 Children.
Xue, M, Wang, Q, Pang, B, Zhang, X, Zhang, Y, Deng, X, Zhang, Z, Niu, W
Biological trace element research. 2024;(2):442-453
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Abstract
Asthma is one of the most frequent chronic diseases in children, and growing focus is placed on the exploration of attributable risk factors. Currently, no consensus has been reached on the implication of circulating zinc in the development of asthma. We aimed to conduct a meta-analysis to examine the association between circulating zinc and risk for childhood asthma and wheezing. We searched PubMed, Web of Science, EMBASE, and Google Scholar from inception until December 1, 2022. All procedures were performed independently and in duplicate. Random-effects model was adopted to derive standardized mean difference (SMD) and 95% confidence interval (95% CI). Statistical analyses were completed using the STATA software. Twenty-one articles and 2205 children were meta-analyzed. Overall, there was a statistically significant association between circulating zinc and risk for childhood asthma and wheezing (SMD: -0.38; 95% CI: -0.60 to -0.17; I2=82.6%, p<0.001), without evidence of publication bias as revealed by Begg's (p=0.608) and Egger (p=0.408) tests. Subgroup analyses showed that children with asthma or wheezing in Middle Eastern countries had significantly lower circulating zinc levels than controls (SMD: -0.42; 95% CI: -0.69 to -0.14; p<0.001; I2=87.1%). Additionally, average circulating zinc levels in asthma children were 0.41 μg/dl lower than that in controls, and the difference was statistically significant (SMD: -0.41; 95% CI: -0.65 to -0.16; p<0.001; I2=83.7%). By contrast, children with wheezing were 0.20 μg/dl lower than that in controls, and no between-group difference was noted (SMD=-0.20; 95% CI: -0.58 to 0.17; p=0.072; I2=69.1%). Our findings indicated that circulating zinc was associated with a significant risk for childhood asthma and its related symptom wheezing.
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Differences in background environment and fertilization method mediate plant response to nitrogen fertilization in alpine grasslands on the Qinghai-Tibetan Plateau.
He, S, Du, J, Wang, Y, Cui, L, Liu, W, Xiao, Y, Ran, Q, Li, L, Zhang, Z, Tang, L, et al
The Science of the total environment. 2024;:167272
Abstract
Grassland degradation threatens ecosystem function and livestock production, partly induced by soil nutrient deficiency due to the lack of nutrient return to soils, which is largely ascribed to the intense grazing activities. Therefore, nitrogen (N) fertilization has been widely adopted to restore degraded Qinghai-Tibetan Plateau (QTP) grasslands. Despite numerous field manipulation studies investigating its effects on alpine grasslands, the patterns and thresholds of plant response to N fertilization remain unclear, thus hindering the prediction of its influences on the regional scale. Here, we established a random forest model to predict N fertilization effects on plant productivity based on a meta-analysis synthesizing 88 publications in QTP grasslands. Our results showed that N fertilization increased the aboveground biomass (AGB) by 46.51 %, varying wildly among plant functional groups. The positive fertilization effects intensified when the N fertilization rate increased to 272 kg ha-1 yr-1, and decreased after three years of continuous fertilization. These effects were more substantial when applying ammonium nitrate compared to urea. Further, a machine learning model was used to predict plant productivity response to N fertilization. The total explained variance and mean squared residuals ranged from 49.41 to 75.13 % and 0.011-0.058, respectively, both being the highest for grasses. The crucial predictors were identified as climatic and geographic factors, background AGB without N fertilization, and fertilization methods (i.e., rate, form, and duration). These predictors with easy access contributed 62.47 % of the prediction power of grasses' response, thus enhancing the generalizability and replicability of our model. Notably, if 30 % of yak dung is returned to soils on the QTP, the grassland productivity and plant carbon pool are predicted to increase by 5.90-6.51 % and 9.35-10.31 g C m-2 yr -1, respectively. Overall, the predictions of this study based on literature synthesis enhance our understanding of plant responses to N fertilization in QTP grasslands, thereby providing helpful information for grassland management policies. Conflict of interest: The authors declare no conflict of interest.
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Meta-analysis of changes in thiol-disulfide homeostasis during preeclampsia.
Wang, D, Yang, G, You, X, Zhang, Z
Biomolecules & biomedicine. 2024;(1):30-39
Abstract
The present study systematically assessed alterations in thiol-disulfide homeostasis among women with preeclampsia (PE) through meta-analysis. This was conducted as such changes are believed to be associated with the oxidative stress underlying this condition. A comprehensive search of Medline, Web of Science, and Embase databases was conducted from their inception until 22 March 2023, to identify studies comparing levels of native thiol, total thiol, and disulfide between pregnant women with PE and those without PE. Results were pooled using a random-effects model to account for study heterogeneity. The analysis included a total of 631 women diagnosed with PE and 668 healthy pregnant women, encompassing 13 case-control studies and 1 prospective study. Pooled outcomes revealed that women with PE had significantly lower blood levels of native thiol, (mean difference [MD] -51.42 umol/L; 95% confidence interval [CI] -79.75 to -23.10 umol/L; P < 0.001; I2 = 0% and total thiol (MD -65.56 umol/L; 95% CI -104.97 to -26.15 umol/L; P = 0.001; I2 = 0%) compared to the control group. In contrast, no significant difference was observed in blood disulfide levels between the two groups (MD -1.10 umol/L; 95% CI -4.41 to -2.21 umol/L; P = 0.51; I2 = 0%). Subgroup analyses indicated that the results were consistent across studies matched by gestational age and body mass index, as well as those with varying quality scores (P for subgroup differences all > 0.05). In conclusion, women with PE are associated with significantly reduced blood levels of native and total thiols but show no change in blood disulfide levels, suggesting a state of reduced antioxidants in PE.
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Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study.
Liu, C, Zheng, S, Gao, H, Yuan, X, Zhang, Z, Xie, J, Yu, C, Xu, L
European journal of nutrition. 2023;(1):379-383
Abstract
BACKGROUND AND AIM Prospective cohort studies have suggested that sugar-sweetened beverages (SSBs) intake is significantly associated with the risk of colorectal cancer (CRC). However, it remains unclear whether this observed association was susceptible to potential confounding factors due to the long-term development process of CRC, and the risk of CRC associated with sweet beverages has rarely been reported. We aimed to investigate the association between SSBs/sweet beverages and CRC risk. METHODS We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for SSBs and sweet beverages from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from two databases for malignant neoplasms of the colon and the rectum (FinnGen and UK Biobank). The inverse weighted method (IVW) meta-analysis was the main method used to estimate the relationship, and sensitivity analyses were performed with Cochran's Q test, leave-one-out analysis, MR-Egger regression, Steiger filtering, and the MR PRESSO test. RESULTS Genetically predicted SSBs intake was associated with a higher colonic malignant neoplasms risk (odds ratio (OR): 1.013; 95% confidence interval (CI) 1.001, 1.026; P = 0.036) in a combined sample size of 579,986 individuals (4029 cases). Such a significant causal effect of SSBs on rectal malignant neoplasms or sweet beverages on CRC was not observed. CONCLUSION Our findings corroborated a causal association between SSBs and colonic malignant neoplasms risk but did not support such a relationship in the analysis of the rectal malignant neoplasms nor the sweet beverage intake, which might be interpreted with caution and further confirmed.
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Effects of Sn-2-palmitate-enriched formula feeding on infants' growth, stool characteristics, stool fatty acid soap contents and bone mineral content: A systematic review and meta-analysis of randomized controlled trials.
Zhang, Z, Wang, Y, Li, Y, Lin, X, Hong, Z, Huang, J, Zhang, X, Yang, Y, Su, Y
Critical reviews in food science and nutrition. 2023;(30):10256-10266
Abstract
This systematic review and meta-analysis was performed to assess the effects of Sn-2-palmitate-enriched formula feeding on infants' growth, stool characteristics, stool fatty acid (FA) soap contents and bone mineral content (BMC). We searched PubMed, MEDLINE, Embase and Web of Science for randomized controlled trials published up to April 2022. Sixteen studies involving 1,931 infants were included. From each included study, weighted mean differences (WMDs) and 95% confidence intervals (CIs) for each of the above mentioned outcomes were extracted and pooled with a fixed-effects model (I2 ≤ 50%) or a random-effects model (I2 > 50%). Infants fed Sn-2-palmitate-enriched formula exhibited greater weight gains (WMD: 0.81; 95% CI: 0.23, 1.39 g/d; I2 = 0.00%), lower contents of total stool FA soaps (WMD: -3.47; 95% CI: -5.08, -1.86 mg/100 mg; I2 = 0.00%) and higher BMC (WMD: 7.08; 95% CI: 4.05, 10.10; I2 = 0.00%) than infants fed standard formula. However, no difference was observed in these outcomes between infants fed Sn-2-palmitate-enriched formula and those fed human milk. This meta-analysis demonstrated that compared with standard formula feeding, Sn-2-palmitate-enriched formula feeding could effectively promote weight gains, bone mineral accumulation and stool FA soap reduction in infants.
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7.
Agricultural diversification promotes sustainable and resilient global rice production.
He, X, Batáry, P, Zou, Y, Zhou, W, Wang, G, Liu, Z, Bai, Y, Gong, S, Zhu, Z, Settele, J, et al
Nature food. 2023;(9):788-796
Abstract
Rice is a staple food for half of the human population, but the effects of diversification on yields, economy, biodiversity and ecosystem services have not been synthesized. Here we quantify diversification effects on environmental and socio-economic aspects of global rice production. We performed a second-order meta-analysis based on 25 first-order meta-analyses covering four decades of research, showing that diversification can maintain soil fertility, nutrient cycling, carbon sequestration and yield. We used three individual first-order meta-analyses based on 39 articles to close major research gaps on the effects of diversification on economy, biodiversity and pest control, showing that agricultural diversification can increase biodiversity by 40%, improve economy by 26% and reduce crop damage by 31%. Trade-off analysis showed that agricultural diversification in rice production promotes win-win scenarios between yield and other ecosystem services in 81% of all cases. Knowledge gaps remain in understanding the spatial and temporal effects of specific diversification practices and trade-offs.
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Effects of Glucomannan Supplementation on Type II Diabetes Mellitus in Humans: A Meta-Analysis.
Zhang, Z, Zhang, Y, Tao, X, Wang, Y, Rao, B, Shi, H
Nutrients. 2023;(3)
Abstract
The hypoglycemic and lipid-lowering effects of glucomannan are widely known, and it is a potential effective treatment for type II diabetes. In this study, we evaluated the effects of glucomannan supplementation on blood-lipid-related indicators, blood-glucose-related indicators, blood pressure (BP), and body weight (BW) in patients suffering from type II diabetes. We searched databases including PubMed, Cochrane, the comprehensive biomedical research database (Embase), Web of Science, and China National Knowledge Infrastructure (CNKI) for literature on glucomannan and type II diabetes. Six randomized controlled trials (RCTs) were eligible (n = 440 participants) to be included in our analysis. Glucomannan not only reduced the total cholesterol (TC) (MD -0.38 [95% CI: -0.61, -0.15], p = 0.001) and low-density lipoprotein (LDL) levels (MD -0.35 [95% CI: -0.52, -0.17], p < 0.0001) compared with the control group, but also reduced the fasting blood glucose (FBG) (MD -1.08 [95% CI: -1.65, -0.50], p = 0.0002), 2 h postprandial blood glucose (P2hBG) (MD -1.92 [95% CI: -3.19, -0.65], p = 0.003), fasting insulin (FINS) (MD -1.59 [95% CI: -2.69, -0.50], p = 0.004), and serum fructosamine (SFRA) levels (SMD -1.19 [95% CI: -1.74, -0.64], p < 0.0001). Our analysis indicates that glucomannan is an effective nutritional intervention for type II diabetes.
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9.
Circulating Copper and Liver Cancer.
Chen, W, Zhang, Z, Liu, K, Jiang, D, Sun, X, Mao, Y, Li, S, Ye, D
Biological trace element research. 2023;(10):4649-4656
Abstract
The association between circulating copper and the risk of liver cancer has been investigated by previous studies, while the findings were inconsistent. Thus, we aimed to evaluate the association between circulating copper and liver cancer by using meta-analysis and Mendelian randomization (MR). For meta-analysis, PubMed and Web of Science were searched to identify eligible studies published before April 4, 2022. Standardized mean difference (SMD) with 95% confidence interval (CI) in circulating copper level between liver cancer patients and controls were pooled. Furthermore, we selected genetic instruments for circulating copper from a genome-wide association study (GWAS) to conduct MR analysis. The summary statistics related to liver cancer were obtained from two large independent cohorts, UKBB and FinnGen, respectively. MR analysis was performed mainly by inverse-variance weighted (IVW) approach, followed by maximum-likelihood method as sensitivity analysis. In meta-analysis of eight studies, circulating copper was found to be higher in liver cancer patients (SMD: 1.65; 95% CI: 0.65 to 2.65) with high heterogeneity (I2 = 96.40%, P = 0.001). However, inconsistent findings were observed among subgroups with high evidence. In MR analysis, genetically predicted circulating copper was not significantly associated with the risk of liver cancer by IVW in UKBB (OR: 1.38; 95% CI: 0.72 to 2.65) and FinnGen (OR: 1.10; 95% CI: 0.69 to 1.73) separately, and the pooled results produced similar results (OR: 1.18, 95% CI: 0.81 to 1.72). Moreover, non-significant finding was confirmed by using maximum-likelihood method. There is no sufficient evidence to demonstrate that high levels of circulating copper increase the risks of liver cancer.
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Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.
Zheng, Y, Zhang, Z, Tang, P, Wu, Y, Zhang, A, Li, D, Wang, CZ, Wan, JY, Yao, H, Yuan, CS
Frontiers in immunology. 2023;14:1143548
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Plain language summary
Intestinal barrier function is closely related to the pathogenesis of various immune and inflammatory diseases. The intestinal microbiota plays an essential role in maintaining gut homeostasis and functionality in the presence of pro-inflammatory and anti-inflammatory microbes. The aim of this study was to comprehensively evaluate the role of probiotics in contributing to intestinal barrier function, and the related immune function, inflammatory status, and gut microbiota composition. This study was a systematic review of 28 articles (qualitative synthesis), and a meta-analysis of 26 randomised controlled trials. Results showed that probiotics could significantly improve intestinal barrier function according to specific indicators. The meta-analysis also indicated that probiotic supplementation could reduce inflammatory factors. Furthermore, it also demonstrated that probiotics could modulate gut microbiota compositions by elevating the abundances of Bifidobacterium and Lactobacillus. Authors conclude that probiotics could improve intestinal barrier function to some extent, but more high-quality randomised controlled studies are needed to reach a solid conclusion.
Expert Review
Conflicts of interest:
None
Take Home Message:
The probiotics Bifidobacterium and Lactobacillus may be beneficial for health by addressing imbalances in gut bacteria (dysbiosis), reducing inflammation in the gut and improving the integrity and function of the gut barrier
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Probiotics are microorganisms that are considered beneficial to health. The aim of this study was to assess the role of probiotics in protecting intestinal barrier function as well as their effects on the composition of gut microbiota, inflammatory status, and immune function for reducing the risk of related diseases.
Methods
26 randomised controlled trials (RCTs) published between 2005-2021 with a total population of n=1891 (n = 955 Intervention, n = 936 controls)) were included in the meta-analysis. Outcome measures were categorised under indicators relating to intestinal barrier function, inflammatory markers, immune function and microbiota composition. Studies were conducted worldwide with participants being healthcare patients or athletes. Study durations ranged from 3 days to 6 months. Different dosages and forms of probiotics were used. Data was pooled for Bifidobacterium, Lactobacillus, Enterobacteriaceae and Enterococcus species.
Results
Gut barrier function in the probiotic groups was improved as measured by transepithelial resistance (TER) mean difference (MD) 5.27 {95% CI, 3.82 to 6.72, p = < 0.00001], lipopolysaccharide (LPS) standardised mean difference (SMD) -0.47 (95% CI, -0.85 to -0.09, p = 0.02), serum zonulin SMD -1.58 (95% CI,-2.49 to -0.66, p = 0.0007), and endotoxin SMD -3.20 (95% CI, -5.41 to - 0.98, p = 0.005).
The inflammatory markers interleukin 6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-a) were also improved compared to control groups. Lactobacillus (95% CI p=0.02) and Bifidobacterium (95% CI, p=0.01) enhanced microbial composition, however, Enterobacteriaceae and Enterococcus species did not. Immune function as measured by Immunoglobulin A (IgA), Immunoglobulin G IgG and Immunoglobulin M (IgM) were not improved.
Conclusion
The findings of this study suggest that intestinal barrier function and microbial composition could be improved using probiotics. They were also found to help alleviate inflammation. Further studies of high quality are however needed to confirm these results.
No conflicts of interest were reported.
Clinical practice applications:
The use of the probiotics Bifidobacterium and Lactobacillus may be beneficial for:
- supporting the integrity of gut barrier function
- improving the composition of gut microbiota
- lowering inflammation
Considerations for future research:
High heterogeneity between studies may affect the applicability of the results. Future research development should focus on the following areas:
- testing methods
- study durations
- measuring indicators
- the type and dose of probiotics
Abstract
BACKGROUND Probiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted. METHODS Four major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses. RESULTS Meta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus. CONCLUSION The present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion. CLINICAL TRIAL REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822.