Hai-yin Jiang

Altered fecal microbiota composition in patients with major depressive disorder

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Use of Selective Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Bleeding: A Systematic Review and Meta-analysis

BACKGROUND & AIMS Selective serotonin reuptake inhibitors (SSRIs) are used to treat various psychiatric disorders. However, there are concerns that SSRIs increase the risk for upper gastrointestinal bleeding (UGIB). METHODS We performed a systematic review and meta-analysis of controlled observational studies to determine whether SSRI use affects the risk for UGIB. Our analysis included all observational studies that compared UGIB development among patients receiving SSRIs vs no treatment. We calculated pooled odds ratios using random- and fixed-effects models. RESULTS A total of 22 studies (6 cohort and 16 case-control studies) involving more than 1,073,000 individuals were included in our meta-analysis. In comparing SSRI users with patients who had not taken SSRIs, the odds for developing UGIB were 1.55-fold higher (odds ratio, 1.55; 95% confidence interval, 1.35-1.78). In subgroup analyses, the association was greatest for patients who received concurrent therapy with nonsteroidal anti-inflammatory or antiplatelet drugs; we found no significant increase in the risk of developing UGIB among patients receiving concurrent acid-suppressing drugs. CONCLUSIONS SSRI use was associated with an almost 2-fold increase in the risk of developing UGIB, especially among patients at high risk for GI bleeding (concurrent use of nonsteroidal anti-inflammatory or antiplatelet drugs). This risk might be reduced significantly by concomitant use of acid-suppressing drugs.

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.

Decreased Diversity of the Oral Microbiota of Patients with Hepatitis B Virus-Induced Chronic Liver Disease: A Pilot Project.

Increasing evidence suggests that altered gut microbiota is implicated in the pathogenesis of hepatitis B virus-induced chronic liver disease (HBV-CLD). However, the structure and composition of the oral microbiota of patients with HBV-CLD remains unclear. High-throughput pyrosequencing showed that decreased oral bacterial diversity was found in patients with HBV-CLD. The Firmicutes/Bacteroidetes ratio was increased significantly, which indicated that dysbiosis of the oral microbiota participated in the process of HBV-CLD development. However, the changing patterns of the oral microbiota in patients with HBV-induced liver cirrhosis (LC) were almost similar to patients with chronic hepatitis B (CHB). HBV infection resulted in an increase in potential H2S- and CH3SH-producing phylotypes such as Fusobacterium, Filifactor, Eubacterium, Parvimonas and Treponema, which might contribute to the increased oral malodor. These key oral-derived phylotypes might invade into the gut as opportunistic pathogens and contribute to altering the composition of the gut microbiota. This study provided important clues that dysbiosis of the oral microbiota might be involved in the development of HBV-CLD. Greater understanding of the relationships between the dysbiosis of oral microbiota and the development of HBV-CLD might facilitate the development of non-invasive differential diagnostic procedures and targeted treatments of HBV-CLD patients harbouring specific oral phylotypes.

Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a systematic review and meta-analysis

OBJECTIVES Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis. METHODS A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile. RESULTS This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009). CONCLUSIONS Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.

Immune response to hepatitis B vaccination among people with inflammatory bowel diseases: A systematic review and meta-analysis

INTRODUCTION The response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low and varies markedly. We performed a systematic review and meta-analysis to determine the response rate to HBV vaccination and identified the factors predictive of an immune response. METHODS We searched PubMed, Cochrane Library, and Embase databases, and reviewed the titles and abstracts of studies on the efficacy of HBV vaccination in IBD patients performed through July 2016. Anti-HBs levels>10IU/L was considered to be an effective immune response. The primary outcome measure was the response rate to HBV vaccination after series completion, and the secondary outcome was identification of factors at baseline predictive of an immune response. RESULTS Thirteen studies including 1688 patients were eligible for inclusion. Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53-69). Young age (mean difference [MD]: -5.7; 95% CI: -8.46, -2.95) and vaccination during disease remission (relative risk [RR]: 1.62; 95% CI: 1.15-2.29) were associated with a positive response to HBV vaccination. In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95% CI: 1.08-1.63) or anti-tumor necrosis factor-α (anti-TNF-α) (RR: 1.57; 95% CI: 1.19-2.08) therapy. CONCLUSIONS Based on this meta-analysis, only three of five IBD patients will show a serological response to HBV vaccination. Vaccination should be performed at the time of IBD diagnosis, during disease remission, or before starting immunosuppressive therapy.

Use of Antipsychotics and Risk of Myocardial Infarction: A Systematic Review and Meta‐analysis

AIM There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS We performed a systematic review and meta-analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION The findings of this meta-analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users.

Gut microbiota profiles in treatment-naïve children with attention deficit hyperactivity disorder

HighlightsWe characterized the gut microbiota profiles in treatment‐naive children with ADHD.Faecalibacterium were decreased in children with ADHD.A negative correlation was found between Faecalibacterium and ADHD severity. Backgrounds: Although increasing evidence suggests a role for the gut microbiota in neurodevelopment, the actual structure and composition of microbiota in children with attention‐deficit/hyperactivity disorder (ADHD) remain unclear. Methods: Thus, the present study aimed to define the characteristics of gut microbiota in treatment‐naive children with ADHD and to assess their relationship with the severity of ADHD symptoms. High‐throughput pyrosequencing was used to investigate the microbiota composition in fecal matter from 51 children with ADHD and 32 healthy controls (HC). Results: An operational taxonomical unit (OTU)‐level analysis revealed a significant decrease in the fractional representation of Faecalibacterium in children with ADHD compared to HC. In individuals with ADHD, the abundance of Faecalibacterium was negatively associated with parental reports of ADHD symptoms. However, there was no significant difference in alpha diversity between the ADHD and control groups. Conclusions: This present findings support the involvement of microbiota alteration in psychiatric diseases and Faecalibacterium may represent a potential novel marker of gut microbiota in ADHD. Future studies are needed to validate these findings and to elucidate the temporal and causal relationships between these variables.

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis

Purpose Previous studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients. Results HCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92–3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81–2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761–2.260). Materials and Methods We conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients. Conclusions Serum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.PURPOSE Previous studies have supported an association between serum insulin-like growth factor 1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients. RESULTS HCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92-3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81-2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761-2.260). MATERIALS AND METHODS We conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients. CONCLUSIONS Serum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.

The Effect of Probiotic Treatment on Patients Infected with the H7N9 Influenza Virus.

Background A novel avian-origin influenza A (H7N9) virus emerged and spread among humans in Eastern China in 2013. Prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. This study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the H7N9 virus. Methods This is a retrospective study in archival samples. Between April 1 and May 10, 2013, 113 stool, sputum, and blood specimens were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to determine the composition of the patient microbiomes. Microbial diversity was calculated using Gel-Pro analyzer and Past software. Cluster analysis of DGGE pattern profiles was employed to create a phylogenetic tree for each patient, and multidimensional scaling (MDS) and principal component analysis (PCA) were performed to visualize relationships between individual lanes. Results Five patients had secondary infections, including Klebsiella pneumonia, Acinetobacter baumanii and Candida albicans infection. The DGGE profiles of fecal samples obtained at different time points from the same individual were clearly different, particularly for patients with secondary infections. Shannon’s diversity index and evenness index were lower in all infected groups compared to the control group. After B. subtilis and E. faecium or C. butyricum administration, the fecal bacterial profiles of patients who had not been treated with antibiotics displayed a trend of increasing diversity and evenness. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients, but administration of B. subtilis and E. faecium appeared to reduce/ameliorate secondary infection in one patient. Conclusion H7N9 infection might decrease intestinal microbial diversity and species richness in humans. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients. B. subtilis and E. faecium may also play a role in reducing/ameliorating secondary infection in these patients.