-
Brain, Behavior, and Immunity Oct 2023The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS.
METHODS
Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases.
RESULTS
METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues.
CONCLUSIONS
Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mental Disorders
PubMed: 37557965
DOI: 10.1016/j.bbi.2023.08.003 -
International Journal of Molecular... Feb 2024CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a...
CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. (logLDA score = 4.39) and (logLDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with (OR: 5.73; 95% CI: 1.32-29.55; = 0.022) and with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; = 0.110). Additionally, was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (logLDA score = 2.88) and II (logLDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species ( and ) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.
Topics: Humans; Male; Middle Aged; Gastrointestinal Microbiome; Prospective Studies; Adenosine; Antibodies, Neutralizing; Antibodies, Viral; COVID-19 Vaccines; Vaccines, Inactivated
PubMed: 38473829
DOI: 10.3390/ijms25052583