Most previous studies in the pathophysiology of major depressive disorder (MDD) focused on fecal samples, which limit the identification of the gut mucosal and luminal microbiome in depression. Here, we address this knowledge gap. Male cynomolgus macaques (Macaca fascicularis) were randomly assigned to a chronic unpredictable mild stress (CUMS) group, or to an unstressed control group. Behavioral tests were completed in both groups. At endpoint, microbe composition of paired mucosal and luminal samples from cecum, ascending, transverse, and descending colons were determined by 16S ribosomal RNA gene sequencing. The levels of 34 metabolites involved in carbohydrate or energy metabolism in luminal samples were measured by targeted metabolomics profiling. CUMS macaques demonstrated significantly more depressive-like behaviors than controls. We found differences in mucosal and luminal microbial composition between the two groups, which were characterized by Firmicutes and Bacteriodetes at the phylum level, as well as Prevotellaceae and Lachnospiraceae at the family level. The majority of discriminative microbes correlated with the depressive-like behavioral phenotype. In addition, we found 27 significantly different microbiome community functions between the two groups in mucosa, and one in lumen, which were mainly involved in carbohydrate and energy metabolism. A total of nine metabolites involved in these pathways were depleted in CUMS animals. Together, CUMS macaques with depressive-like behaviors associated with distinct alterations of covarying microbiota, carbohydrate and energy metabolism in mucosa and lumen. Further studies should focus on the mucosal and luminal microbiome to provide a deeper spatiotemporal perspective of microbial alterations in the pathogenesis of MDD.

BackgroundOlder adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors.MethodsRandomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456).ResultsOf the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55−89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77−96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80−4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80−96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82−93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45−99.98) and GMT (SMD 6.20, 95% CI: 2.02−10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38−1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22).ConclusionCOVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

Introduction Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine in treating MDD based on real-world data. Methods A systematic search of eight electronic databases was performed from inception until October 2022 to identify real-world studies, excluding randomized controlled trials. We conducted subgroup, meta-regression, sensitivity analyses, publication bias and quality assessments using the random-effects model. The effects were summarized by rates or standardized mean difference (SMD) with 95% confidence intervals (CI). Results Of the 870 records identified, 11 studies (3139 participants) and 10 case reports or series were eligible for inclusion. Vortioxetine significantly relieved depression symptoms as assessed by both patients (SMD 2.25, 95% CI: 1.60−2.89) and physicians (SMD 3.73, 95% CI: 2.78−4.69). Cognitive function (1.86, 1.11−2.62) and functional disability (1.71, 1.14−2.29) were similarly markedly improved. Subgroup and meta-regression analyses showed that geographic location and medication regimen (whether combined with other antidepressants) were crucial factors influencing the effectiveness, potentially contributing to significant heterogeneity. The estimated response and remission rates were 66.4% (95% CI: 51.2%−81.5%) and 58.0% (48.9%−67.1%), respectively. Vortioxetine was well-tolerated with a pooled dropout rate of 3.5% (1.8%−5.8%), and the most common adverse event was nausea, with an estimated rate of 8.9% (3.8%−15.8%). Limitations The study has some limitations, including significant heterogeneity and limited evidence for some outcomes. Conclusions Vortioxetine is effective, well-tolerated, and safe for treating MDD in clinical practice, with significant improvements observed in depressive severity, cognitive function, and functioning. Future studies should directly compare vortioxetine with other antidepressants in real-world settings to further evaluate its clinical utility.