Adjudicative efficacy of Bifidobacterium animalis subsp. lactis BLa80 in treating acute diarrhea in children: a randomized, double-blinded, placebo-controlled study.

The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis BLa80, as an adjunct treatment for diarrhea in children with a randomized, double-blinded, placebo-controlled study design. Eligible diarrheal children, aged 0-3 years without the need for antibiotic treatment based on clinical diagnosis when recruited, were randomized into the intervention group (IG, n = 58, with probiotic) or the control group (CG, n = 53, placebo). The primary assessment was the duration of diarrhea. Fecal samples were collected for biochemical index measurement, analysis of gut microbiome composition, and prediction of gene family abundances. The total duration of diarrhea in the IG (122.6 ± 13.1 h) was significantly shorter than in the CG (148.4 ± 17.6 h, p < 0.001). More children in the IG showed improvements in diarrhea compared to the CG, both in intention-to-treat analysis (81.7% vs. 40.0%, p < 0.001) and per protocol analysis (84.4% vs 45.3%, p < 0.001). Cathelicidin level in the IG was significantly higher than that in the CG after the intervention (4415.00 ± 1036.93 pg/g vs. 3679.49 ± 871.18 pg/g, p = 0.0175). The intervention led to an increased abundance of Bifidobacterium breve and Collinsella aerofaciens species, higher alpha-diversity (p < 0.05), and enrichment of functional genes in the gut microbiota related to immunity regulation. Administration of BLa80 at a dose of 5 × 109 CFU/day resulted in a shorter duration of diarrhea and alterations in gut microbiome composition and gene functions.

Adjunctive efficacy of Bifidobacterium animalis subsp. lactis XLTG11 for functional constipation in children.

Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) (F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum, Bifidobacterium breve, and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 1010 CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism-related genes.

Association of gut microbiota and dietary component intake with COVID-19: A mendelian randomization study.

BACKGROUND: Growing evidence has indicated that alterations in the gut microbiota and nutritional quality of dietary intake were associated with COVID-19. Whether these associations reflect causality is still unknown. METHODS: We performed a two-sample Mendelian randomization analysis using genetic variants as instrumental variables for gut microbiota, dietary component intake, and COVID-19. FINDINGS: We found that the Ruminococcustorques group genus was significantly associated with COVID-19. The Ruminococcaceae UCG013 genus and Ruminococcus1 genus were suggestively associated with COVID-19. The Actinobacteria class, Bifidobacteriales order, Bifidobacteriaceae genus, R. group, and Tyzzerella3 genus were potentially associated with severe COVID-19. COVID-19 was significantly associated with the Lachnospira genus, Oscillospira, and RuminococcaceaeUCG009 genus and potentially associated with the Victivallis genus. Severe COVID-19 was significantly associated with the Turicibacter and Olsenella genus and potentially associated with Ruminococcus1, CandidatusSoleaferrea, and Parasutterella genus. Moreover, processed meat intake was significantly associated with COVID-19. Beef intake was suggestively associated with COVID-19. Salt added to food intake, and fresh fruit intake was suggestively associated with severe COVID-19. CONCLUSIONS: Our findings provide evidence supporting a causal effect of gut microbiota and dietary intake on COVID-19. We also found the causal effect of COVID-19 on the alteration of gut microbiota.

Adjunctive efficacy of Lactis XLTG11 for Acute diarrhea in children: A randomized, blinded, placebo-controlled study.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of Bifidobacterium animalis sp. Lactis XLTG11, as an adjunctive treatment for acute watery diarrhea in children, using a randomized, double-blinded, placebo-controlled study design. METHOD: Eligible children with diarrhea were randomly assigned into one of two groups: an intervention group (IG, n = 35), which received conventional treatment plus the probiotic, and a control group (CG, n = 35), which received only conventional treatment. Fecal samples were collected from all children before and after the intervention to measure biochemical indices and analyze gut microbiome (GM) composition. RESULT: The duration of diarrhea (121.3 ± 11.5 h) and hospital length of stay (3.4 ± 1.1 d) in the IG were significantly shorter than those in the CG (133.4 ± 14.1 h and 4 ± 1.3 d, respectively; P < 0.001 and P = 0.041, respectively). A higher percentage of children in the IG showed improvements compared with the CG (57.1% versus 25.7%, P < 0.001). The calprotectin level in the IG was significantly lower than that in the CG after the intervention (928.91 ± 158.90 ng/g versus 1029.86 ± 133.25 ng/g, P = 0.028). XLTG11 administration led to a higher abundance of species B. longum and < breve, increased α-diversity of the GM (P < 0.05), and upregulated the functional genes of the GM related to immunity and nutrient absorption. CONCLUSIONS: Administration of XLTG11 at a dose of 1 × 1010 CFU/d was effective in reducing the duration of diarrhea, inducing beneficial changes in GM composition and gene functions.

Iron status and obesity-related traits: A two-sample bidirectional Mendelian randomization study.

Background: The association between iron status and obesity-related traits is well established by observational studies, but the causality is uncertain. In this study, we performed a two-sample bidirectional Mendelian randomization analysis to investigate the causal link between iron status and obesity-related traits. Methods: The genetic instruments strongly associated with body mass index (BMI), waist-hip ratio (WHR), serum ferritin, serum iron, transferrin saturation (TSAT), and total iron-binding capacity (TIBC) were obtained through a series of screening processes from summary data of genome-wide association studies (GWAS) of European individuals. We used numerous MR analytical methods, such as inverse-variance weighting (IVW), MR-Egger, weighted median, and maximum likelihood to make the conclusions more robust and credible, and alternate methods, including the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis to evaluate the horizontal pleiotropy and heterogeneities. In addition, the MR-PRESSO and RadialMR methods were utilized to identify and remove outliers, eventually achieving reduced heterogeneity and horizontal pleiotropy. Results: The results of IVW analysis indicated that genetically predicted BMI was associated with increased levels of serum ferritin (ß: 0.077, 95% CI: 0.038, 0.116, P=1.18E-04) and decreased levels of serum iron (ß: -0.066, 95% CI: -0.106, -0.026, P=0.001) and TSAT (ß: -0.080, 95% CI: -0.124, -0.037, P=3.08E-04), but not associated with the levels of TIBC. However, the genetically predicted WHR was not associated with iron status. Genetically predicted iron status were not associated with BMI and WHR. Conclusions: In European individuals, BMI may be the causative factor of serum ferritin, serum iron, and TSAT, but the iron status does not cause changes in BMI or WHR.

COVID-19 and the risk of Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on the healthcare system, economy, and society. Studies have reported that COVID-19 may cause various neurologic symptoms, including cognitive impairment. We aimed to assess the causal effect of COVID-19 on neurodegenerative diseases using two-sample Mendelian randomization (MR) study. METHODS: Genetic variants were obtained from genome-wide association studies (GWAS) summary-level data and meta-analyses. We used the inverse variance-weighted (IVW) method as the primary analysis to estimate causal effects. Sensitivity analyses were performed to make the conclusions more robust and reliable. RESULTS: We found that the COVID-19 infection phenotype was associated with a higher risk of AD and inverse associated with the risk of ALS and MS. The hospitalized COVID-19 phenotype was associated with the risk of AD and wasn't associated with ALS and MS. We also found that the severe COVID-19 (main analysis) phenotype was associated with the AD outcome from UK biobank datasets but was not associated with other outcomes. The severe COVID-19 infection phenotype, the severe COVID-19 (subtype analysis) phenotype and the hospitalization risk of COVID-19 were not associated with each outcome. CONCLUSION: This MR study suggests a potential association between genetically predicted COVID-19 and a higher risk of AD and a reduced risk of ALS and MS. Further elucidations of this association and underlying mechanisms may inform public health messages to prevent COVID-19 and AD.

Origin and Genesis of the Permain Hydrocarbon in the Northeast of the Dongdaohaizi Depression, Junggar Basin, China.

Dongdaohaizi area is an important hydrocarbon-rich depression in the Junggar Basin. Early resource evaluation has revealed that it has superior hydrocarbon generation conditions. No major exploration breakthrough has been observed in the hydrocarbon from the Permian Pingdiquan Formation source rocks, which are widely distributed and have a large sedimentary thickness. The unclear recognition of the genesis, the sources, and the hydrocarbon evolution history of the formation seriously restricted further exploration and development. Sixty-four samples were acquired during the study, consisting of 30 source rocks, 13 crude oil samples, and 21 natural gas samples. Studying the geochemical characteristics of the source rock extract and the surrounding structural crude oil in the Dongdaohaizi Depression, the differences in the stable carbon isotope, the biomarker compound, and the molecular relative composition of the three sets of main source rock products in the research fields are summarized. The results reflect that the drying coefficient of natural gas in the study area is generally low, and the fractional distillation value of methane and ethane is 0.32, which is most likely due to the loss of oil and gas migration and the mixing of different types of natural gases. The carbon isotope value is relatively low, with the Pr/Ph being generally less than 3.0. The content of sterane C29 is the highest in the relative composition of steranes, followed by the content of sterane C28, which together account for more than 80% of the total sterane content, and then followed by a lower content of C27 sterane, accounting for only 5-20% of the total content, which generally conforms to the characteristics of Permian Pingdiquan Formation source rock products. The carbon isotope value of crude oil ranges from -30.94 to -28.31‰, which is different from the characteristics of typical Permian source rocks (values range from -34.49 to -28.21‰), while it is related to typical Carboniferous products (values range from -29.98 to -24.1‰), indicating that small amounts of Carboniferous source rock products were mixed in different degrees in the Dinan fault area. According to the distribution law of oil and gas, the geochemical characteristics and hydrocarbon sources were considered the oil source in the east of the Dongdaohaizi Depression, mainly from the source rocks of the Permian Pingdiquan Formation. The products of the peak period of hydrocarbon generation in the source rocks of the Pingdiquan Formation have not been transported to the high structural positions on a large scale to form reservoirs. They may still exist in the deep part of the Depression and the slope area. The low-amplitude structural and lithologic traps in the slope area of the Dongdahaizi Depression are promising targets for finding the products of the peak period of hydrocarbon generation. This is of great significance to reveal the Permain hydrocarbon evolution in the Junggar Basin and guide further research on the oil-source correlation of natural gas from the paleo-strata.

Fibrinogen in Alzheimer's Disease, Parkinson's Disease and Lewy Body Dementia: A Mendelian Randomization Study.

Fibrinogen is reportedly associated with neurodegenerative diseases (NDs), but the underlying causality remains controversial. Using Mendelian randomization (MR), this study aimed to assess the causal association between fibrinogen and Alzheimer's disease (AD), Parkinson's disease (PD), and Lewy body dementia (LBD). Genetic variants associated with fibrinogen and γ-fibrinogen were selected and used as instrumental variables. The effect estimates of the main analysis were obtained by inverse-variance weighting (IVW), complemented by sensitivity analyses to verify model assumptions, and multivariable MR was conducted to control for potential pleiotropic effect. Two-step MR was performed to assess the causal association through mediators. The main analysis suggested no causal association between genetically predicted plasma fibrinogen and γ-fibrinogen levels and the risk of AD, PD, and LBD. The effect estimates did not change in the follow-up sensitivity analyses and MVMR. However, the two-step MR analysis provides evidence that fibrinogen may contribute to the risk of AD via CRP levels. There was an inverse effect of adult height levels on the risk of AD. Our results support the effects of fibrinogen on the risk of AD through increasing plasma CRP levels. Our study found no evidence to support the effects of genetically determined fibrinogen and γ-fibrinogen levels on the risk of PD and LBD. Additionally, our findings suggested an inverse association between genetically determined adult height levels and the risk of AD. Future studies are needed to elucidate the underlying mechanisms and their clinical applications.

Dose effect of bovine lactoferrin fortification on diarrhea and respiratory tract infections in weaned infants with anemia: A randomized, controlled trial.

OBJECTIVE: The aim of this study was to explore the dose effect of bovine lactoferrin (bLF) fortification on the morbidity of diarrhea and respiratory tract infections in weaned infants with anemia. METHODS: A total of 108 infants with anemia, who were exclusively breast fed at 4 to 6 mo and weaned and formula fed at 6 to 9 mo, were recruited. The eligible infants were randomly assigned to fortified group 0 (FG0), fortified group 1 (FG1), or fortified group 2 (FG2) and were given formula fortified with 0 mg/100 g, 38 mg/100 g, and 76 mg/100 g of bLF, respectively, for 3 mo. The morbidity of diarrhea and respiratory tract infections (RTIs), the duration of respiratory and diarrhea-related illnesses, and the levels of fecal human beta-defensin 2 (HBD-2), cathelicidin LL-37 (LL-37), secretory IgA (sIgA), butyrate, and calprotectin were assessed. RESULTS: After the exclusion of 12 dropouts, the primary outcome measures, including episodes and duration of diarrhea and RTIs during the intervention, were obtained from 96 infants (35, 33, and 28 in FG0, FG1, and FG2, respectively). Compared with infants in FG0, there was a lower morbidity of rhinorrhea, wheezing, and skin rash among infants in FG1 (P < 0.05) and a lower morbidity of respiratory-related illness and wheezing among infants in FG2 (P < 0.05). Furthermore, a lower morbidity of diarrhea-related illness, diarrhea, vomiting, and nausea was observed among infants in FG2 than those in the other two groups (P < 0.05). In addition, the FG1 infants had a lower morbidity of vomiting and nausea than the FG0 infants (P < 0.05). The HBD-2, LL-37, sIgA, and calprotectin levels were significantly higher whereas the butyrate level was significantly lower in the FG2 infants than in infants in the other two groups after 3 mo of intervention (P < 0.05). CONCLUSIONS: The bLF-fortified formula was effective in reducing the morbidity of diarrhea and RTIs in infants with anemia, with the 76 mg/100 g bLF-fortified formula exhibiting a stronger effect. The bLF fortification could be a new strategy for the prevention of diarrhea and RTIs in infants with anemia.

Identification of key genes and biological pathways in lung adenocarcinoma via bioinformatics analysis.

Lung adenocarcinoma (LUAD) accounts for the majority of cancer-related deaths worldwide. Our study identified key LUAD genes and their potential mechanism via bioinformatics analysis of public datasets. GSE10799, GSE40791, and GSE27262 microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database. The RobustRankAggreg package was used to perform a meta-analysis, and 50 upregulated genes and 87 downregulated genes overlapped in three datasets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Furthermore, protein-protein interaction (PPI) networks of the differentially expressed genes (DEGs) were built by the Search Tool for the Retrieval of Interacting Genes (STRING) and 22 core genes were identified by Molecular Complex Detection (MCODE) and visualized with Cytoscape. Subsequently, these core genes were analyzed by the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA). The results showed that all 22 genes were significantly associated with reduced survival rates. For GEPIA, the expression of only one gene was not significantly different between LUAD tissues and normal tissues. A KEGG pathway enrichment reanalysis of the 21 genes identified five key genes (CCNB1, BUB1B, CDC20, TTK, and MAD2L1) in the cell cycle pathway. Finally, the Comparative Toxicogenomics Database (CTD) website was used to explore the relationship between these key genes and certain drugs. Based on the bioinformatics analysis, five key genes were identified in LUAD, and drugs closely associated these genes can provide clues for the treatment and prognosis of LUAD.

Integrated analysis of differentially expressed long noncoding RNAs and mRNAs associated with high-fat diet-induced hepatic insulin resistance in mice.

BACKGROUND: Hepatic insulin resistance (IR) is an early pathological characteristic of many metabolic diseases, such as type 2 diabetes. Long noncoding RNAs (lncRNAs) have been identified as mediators of IR and related diseases. However, the roles of lncRNAs in hepatic IR remain largely unknown. METHOD: High-throughput sequencing was performed on ten liver tissue samples from five normal diet (ND)-fed mice and five high-fat diet (HFD)-induced hepatic IR mice, respectively. lncRNAs and mRNAs that were differentially expressed (DE) between the two groups were identified by bioinformatic analyses. Seven DE lncRNAs were validated by quantitative real-time PCR (q-PCR). The potential functions of the DE lncRNAs were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of target genes. In addition, integrated analysis was performed for the DE lncRNAs and mRNAs to predict their interaction relationships. RESULTS: A total of 232 DE lncRNAs were identified in the HFD-induced hepatic IR mice compared with the ND-fed mice. These DE lncRNAs included 108 upregulated and 124 downregulated lncRNAs, and 7 of the DE lncRNAs were validated by q-PCR. In addition, 291 DE mRNAs including 166 upregulated and 125 downregulated mRNAs were identified in the HFD group. Furthermore, target genes of the DE lncRNAs were predicted, and functional enrichment results showed that the enriched genes were involved in IR- and glycolipid metabolism-related processes. Additionally, the coexpression network was also constructed to further reflect the potential functions of the DE lncRNAs. CONCLUSION: The study describes the expression profiles of lncRNAs and mRNAs and the functional networks involved in HFD-induced hepatic IR. These findings may provide a new perspective for the study of lncRNAs in hepatic IR- and glycolipid metabolism-related diseases.

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis.

Hepatocellular carcinoma (HCC) is a widespread, common type of cancer in Asian countries, and the need for biomarker-matched molecularly targeted therapy for HCC has been increasingly recognized. However, the effective treatment for HCC is unclear. Therefore, identifying additional hub genes and pathways as novel prognostic biomarkers for HCC is necessary. In this study, the expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus (GEO), including 132 HCC and 90 noncancerous liver tissues. Differentially expressed genes (DEGs) between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. In total, 109 DEGs were identified in these datasets, including 24 upregulated genes and 85 downregulated genes. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) preliminary analyses of the DEGs were performed using DAVID. The protein-protein interaction (PPI) network of the DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Module analysis of the PPI network was performed using MCODE to get hub genes. Moreover, the influence of the hub genes on overall survival was determined with Kaplan-Meier plotter. All hub genes were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and KEGG. Overall, the hub genes DTL, CDK1, CCNB1, RACGAP1, ECT2, NEK2, BUB1B, PBK, TOP2A, ASPM, HMMR, RRM2, CDKN3, PRC1, and ANLN were upregulated in HCC, and the survival rate was lower for HCC with increased expression of these hub genes. CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway, and CCNB1, CDK1, and BUB1B were enriched in the cell cycle. In brief, we screened 15 hub genes and pathways to identify potential prognostic markers for HCC treatment. However, the specific occurrence and development of HCC with expression of the hub genes should be verified in vivo and in vitro.

High-throughput sequencing of small RNAs and analysis of differentially expressed microRNAs associated with high-fat diet-induced hepatic insulin resistance in mice.

BACKGROUND: Hepatic insulin resistance (IR) plays a crucial role in the development of many metabolic diseases, such as type 2 diabetes. MicroRNAs (miRNAs) are involved in the pathogenesis of IR and related diseases; however, studies of miRNAs in hepatic IR are limited. METHOD: In this study, we adopted a high-throughput sequencing approach to construct small RNA libraries in the livers of normal mice and high-fat diet-induced hepatic IR mice. RESULTS: Through analysis of data, 107 known and 56 novel miRNAs were identified as differentially expressed miRNAs between the two groups. Additionally, bioinformatics methods were used to predict targets of the differentially expressed miRNAs and to explore the potential downstream Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways. Meanwhile, some differentially expressed miRNAs (miR-34a-5p, miR-149-5p, miR-335-3p, miR-10b-5p, miR-1a-3p, miR-411-5p, and miR-592-5p) were validated by quantitative-time PCR, and their potential target genes related to IR or glycolipid metabolism were also predicted and presented in this study. CONCLUSION: Taken together, our results defined miRNA expression signature that may lead to hepatic IR in mice, and the findings provided a foundation for future studies to further explore the effects and underlying mechanisms of the miRNAs and their target genes in the pathogenesis of hepatic IR and related diseases.