Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis.

CONTEXT: Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions. OBJECTIVE: A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD. DATA SOURCES: Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022. DATA EXACTION: Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305). RESULTS: Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants. CONCLUSION: Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020222305.

Phenotypic and genotypic characterization of antibiotic-resistant Salmonella isolated from humans, aquaculture, and poultry in Sri Lanka: A retrospective study.

BACKGROUND: In Sri Lanka, foodborne diseases caused by nontyphoidal Salmonella are of increasing concern. We therefore aimed to characterize the dominant Salmonella serovars in humans, poultry, and aquaculture through a One Health approach. METHODS: We collected isolates from different sectors, confirmed their identities using PCR, screened their antibiotic resistance profiles, and determined their antibiotic resistance genes based on whole-genome sequencing. RESULTS: Of the 75 Salmonella isolates identified, the majority of serotypes were unidentified. Both Salmonella enterica serovar Enteritidis (S. Enteritidis) and Salmonella enterica serovar Typhimurium (S. Typhimurium) could be isolated from human sources and were also found prevalent in the poultry sector. ST36, ST11 and ST1541 were the dominant serotypes of S. Typhimurium and S. Enteritidis, respectively. Alarmingly, 4% (1/25) of poultry Salmonella isolates were resistant to ciprofloxacin, suggesting an emergence of this phenotype. Moreover, virulence genes were very diverse among S. Enteritidis and S. Typhimurium isolates. CONCLUSIONS: With the diversity of unidentified serotypes found and the detection of emerging resistances, our study highlights the importance of a One Health approach to monitoring antibiotic resistance. For public health initiatives in Sri Lanka to be successful in mitigating salmonellosis, all three sectors - humans, aquaculture, and poultry - must be tackled concomitantly in a coordinated manner under the One Health approach because antibiotic resistance genes, and even specific sequence types, may be able to spread across the aforementioned sectors. We anticipate that our results will inform public health policies in Sri Lanka to tackle foodborne illnesses.

COVID-19 mRNA vaccine-mediated antibodies in human breast milk and their association with breast milk microbiota composition.

Newborns can acquire immunological protection to SARS-CoV-2 through vaccine-conferred antibodies in human breast milk. However, there are some concerns around lactating mothers with regards to potential short- and long-term adverse events and vaccine-induced changes to their breast milk microbiome composition, which helps shape the early-life microbiome. Thus, we sought to explore if SARS-CoV-2 mRNA vaccine could change breast milk microbiota and how the changes impact the levels of antibodies in breast milk. We recruited 49 lactating mothers from Hong Kong who received two doses of BNT162b2 vaccine between June 2021 and August 2021. Breast milk samples were self-collected by participants pre-vaccination, one week post-first dose, one week post-second dose, and one month post-second dose. The levels of SARS-CoV-2 spike-specific IgA and IgG in breast milk peaked at one week post-second dose. Subsequently, the levels of both antibodies rapidly waned in breast milk, with IgA levels returning to baseline levels one month post-second dose. The richness and composition of human breast milk microbiota changed dynamically throughout the vaccination regimen, but the abundances of beneficial microbes such as Bifidobacterium species did not significantly change after vaccination. Additionally, we found that baseline breast milk bacterial composition can predict spike-specific IgA levels at one week post-second dose (Area Under Curve: 0.72, 95% confidence interval: 0.58-0.85). Taken together, our results identified specific breast milk microbiota markers associated with high levels of IgA in the breast milk following BNT162b2 vaccine. Furthermore, in lactating mothers, BNT162b2 vaccines did not significantly reduce probiotic species in breast milk.

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines.

The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.

Longitudinal monitoring reveals the emergence and spread of blaGES-5-harboring carbapenem-resistant Klebsiella quasipneumoniae in a Hong Kong hospital wastewater discharge line.

Testing hospital wastewater (HWW) is potentially an effective, long-term approach for monitoring trends in antimicrobial resistance (AMR) patterns in health care institutions. Over a year, we collected wastewater samples from the clinical and non-clinical sites of a tertiary hospital and from a downstream wastewater treatment plant (WWTP). We focused on the extent of carbapenem resistance among Enterobacteriaceae isolates given their clinical importance. Escherichia coli and Klebsiella spp. were the most frequently isolated Enterobacteriaceae species at all sampling sites. Additionally, a small number of isolates belonging to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), except K. pneumoniae, were detected. Of the 232 Klebsiella spp. isolates, 100 (43.1 %) were multi-drug resistant (MDR), with 46 being carbapenem-resistant. Most of these carbapenem-resistant isolates were K. quasipneumoniae (CRKQ) (n = 44). All CRKQ isolates were isolated from the wastewater of a clinical site that includes intensive care units, which also yielded significantly more multi-drug resistant isolates compared to all other sampling sites. Among the CRKQ isolates, blaGES-5 genes (n = 42) were the primary genetic determinant of carbapenem resistance. Notably, three different CRKQ isolates, collected within the same month in HWW and the influent and effluent flow of the WWTP, shared >99 % sequence similarity between their blaGES-5 genes and between their flanking regions and upstream integron-integrase region. The influent isolate was phylogenetically close to K. quasipnuemoniae isolates from wastewater collected in Japan. Its blaGES-5 gene and surrounding sequences were > 99 % identical to blaGES-24 genes found in the Japanese isolates. Our results suggest that testing samples from sites located closer to hospitals could support antibiotic stewardship programs compared to samples collected further downstream. Moreover, testing samples collected regularly from WWTPs may reflect the local and global spread of pathogens and their resistances.