Search

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the

The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome (psex-difference < 5 × 10−8). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites. The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome (psex-difference < 5 × 10−8). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites.