Ontology highlight
ABSTRACT:
PROVIDER: PRJNA591748 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR10695407_1.fastq.gz | Fastqsanger.gz | |||
| SRR10695407_2.fastq.gz | Fastqsanger.gz | |||
| SRR10695408_1.fastq.gz | Fastqsanger.gz | |||
| SRR10695408_2.fastq.gz | Fastqsanger.gz |
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Project description:The trillions of microorganisms in the human gastrointestinal tract are an underexplored aspect of pharmacology. Despite numerous examples of microbial effects on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the commonly prescribed cardiac glycoside, digoxin, by Eggerthella lenta. Whole genome transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, absent in non-metabolizing E. lenta strains, and predictive of the efficiency of digoxin inactivation by the human gut microbiome. Digoxin inactivation was further enhanced by microbial interactions and inhibited by arginine. Pharmacokinetic studies using gnotobiotic mice revealed that increasing dietary protein reduces the in vivo metabolism of digoxin by E. lenta, with significant changes to drug concentration in the urine and serum. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes. RNA-Seq analysis of Eggerthella lenta cultured with or without digoxin.
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Project description:Kawasaki Disease (KD) is a multisystemic vasculitis of unknown etiology in children. The incidence of KD varies by geographic area and correlates with differences in gut microbiota patterns, with the highest incidence in Asian. This study aimed to investigate alterations in fecal microbiota and assess their relationship with systemic inflammation in KD patients. A total of 59 patients and 55 matched controls were included. Fecal samples were collected at the onset of KD. The V3/V4 regions of 16S rDNA were sequenced using the MiSeq platform. PICRUSt 2 was used to analyze the potential functional pathways involved in gut dysbiosis. Alpha (p<0.042) and beta (p<0.001) diversity in KD were significantly decreased when compared to the control group. After multivariate regression, among the seven critical microbes, increased Bacteroides ovtaus (p=0.016) and decreased Eggerthella lenta (p=0.014) could also predict KD risk using receiver operating characteristic curve (ROC) analysis (Eggerthella lenta: area under the ROC curve, AUC=0.841, odds ratio=23.956; Bacteroides ovatus: AUC=0.816, odds ratio=31.365). Notably, Bacteroides ovatus was positively correlated with blood segment cells (p=0.006), but negatively correlated with blood lymphocytes (p=0.013). After multivariate regression, flavone and flavonol biosynthesis decreased in children with KD (p<0.001). Our results indicated that both Bacteroides ovatus and Eggerthella lenta may deregulate flavone and flavonol biosynthesis, consequently modulating immune cells and potentially triggering KD. This study suggests that alterations in the gut microbiota are closely associated with immune responses and provides a new perspective on the etiology, pathogenesis, and treatment of KD.
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Project description:Adlercreutzia equolifaciens overview
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Project description:Bile acids are not only crucial for the uptake of lipids, but also have widespread systematic ef-fects and shape the gut-microbiome composition. Bile acids can directly shape the gut-microbiome and can be modified by bacteria such as Eggerthella lenta which in turn plays a crucial role in host metabolism and immune response. We cultivated eight strains that represent a simplified human intestinal microbiome and inves-tigated the molecular response to bile acids, co-culturing with Eggerthella lenta and the combina-tion. We observed growth inhibition of particularly gram-positive strains during bile acid stress, which could be alleviated through co-culturing with Eggerthella lenta. The inhibition of growth was related to a decrease in membrane integrity and genotoxic effects of bile acids, which we investigated using zeta potential measurements in combination with proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta alleviated stress through formation of oxidized and epimer-ized bile acids and the molecular response to co-culturing was seen to be strain specific. We also note that we could detect the recently described Microbial Bile Salt Conjugates in our cultures. This study highlights the significance of a potent bile acid modifier and how in-depth molecular analyses are required to decipher cross-communication between gut and host.
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Project description:The trillions of microorganisms in the human gastrointestinal tract are an underexplored aspect of pharmacology. Despite numerous examples of microbial effects on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the commonly prescribed cardiac glycoside, digoxin, by Eggerthella lenta. Whole genome transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, absent in non-metabolizing E. lenta strains, and predictive of the efficiency of digoxin inactivation by the human gut microbiome. Digoxin inactivation was further enhanced by microbial interactions and inhibited by arginine. Pharmacokinetic studies using gnotobiotic mice revealed that increasing dietary protein reduces the in vivo metabolism of digoxin by E. lenta, with significant changes to drug concentration in the urine and serum. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes.
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