Ontology highlight
ABSTRACT:
PROVIDER: PRJNA770818 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microbiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. However, their involvement in the gut-brain axis has been poorly investigated. In this study, we aimed to investigate the cargo capacity of MEVs for bioactive metabolites and their interactions with the host. Metabolomics analysis identified various neuro-related compounds encapsulated within the 28 MEVs, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines. 29 Metaproteomics unveiled an enrichment of enzymes involved in neuronal metabolism, primarily in the glutamine/glutamate/GABA pathway. The detected neuro-related proteins and metabolites were correlated with Bacteroides spp. A GABA-producing Bacteroides isolate, B. finegoldii, released EVs with a high GABA content (4 µM) as opposed to a low GABA-producing isolate, Phocaeicola massiliensis. MEVs exhibited a dose-dependent paracellular transport and were endocytosed by Caco-2 and hCMEC/D3 cells. RNA-Seq analyses showed that MEVs stimulate several immune pathways while suppressing cell apoptosis process. The in vivo biodistribution confirmed the presence of MEVs in the brain, liver, stomach, and spleen. Overall, our results highlight the ability of MEVs to cross the intestinal and blood-brain barriers to deliver their cargoes to distant organs, including the brain, where it may modulate the organ functionalities. MEVs could be an integral part of microbiome-host communications, with potential implication for the gut-brain axis.
2024-11-05 | PXD045162 | Pride
Project description:Tertiary lymphoid structures (TLS) in the tumour microenvironment have been linked to positive clinical outcomes and responses to immune checkpoint inhibitors (ICI) in various cancers, including clear cell renal cell carcinoma (ccRCC) and soft tissue sarcoma (STS). However, a significant proportion of patients do not respond to ICI despite the presence of TLS. Our study unravels gamma-aminobutyric acid (GABA), a neurotransmission inhibitor, as a modulator of ICI resistance in TLS-positive tumours. By leveraging household and public multi-omic data, we demonstrated that GABA is upregulated in TLS-positive ccRCC and STS tumours from non-responders to ICI. In metastatic ccRCC, TLS from non-responders were distinguished from responders by a dysfunctional immune activation and a close proximity to GABA-producing proximal tubule-like tumour cells. The addition of a competitive inhibitor of GABA synthesis, 3-mercaptopropionic acid, significantly improved tumour control when compared to anti-PD1 alone when intra-tumourally injected in a mouse model of STS. Overall, our findings highlight GABA as a novel determinant of non-response to ICI in tumours harboring TLS, suggesting potential new approaches for patient stratification and personalized therapeutic strategies that could be applicable beyond metastatic ccRCC and STS.
2026-02-28 | GSE273952 | GEO
Project description:Tertiary lymphoid structures (TLS) in the tumour microenvironment have been linked to positive clinical outcomes and responses to immune checkpoint inhibitors (ICI) in various cancers, including clear cell renal cell carcinoma (ccRCC) and soft tissue sarcoma (STS). However, a significant proportion of patients do not respond to ICI despite the presence of TLS. Our study unravels gamma-aminobutyric acid (GABA), a neurotransmission inhibitor, as a modulator of ICI resistance in TLS-positive tumours. By leveraging household and public multi-omic data, we demonstrated that GABA is upregulated in TLS-positive ccRCC and STS tumours from non-responders to ICI. In metastatic ccRCC, TLS from non-responders were distinguished from responders by a dysfunctional immune activation and a close proximity to GABA-producing proximal tubule-like tumour cells. The addition of a competitive inhibitor of GABA synthesis, 3-mercaptopropionic acid, significantly improved tumour control when compared to anti-PD1 alone when intra-tumourally injected in a mouse model of STS. Overall, our findings highlight GABA as a novel determinant of non-response to ICI in tumours harboring TLS, suggesting potential new approaches for patient stratification and personalized therapeutic strategies that could be applicable beyond metastatic ccRCC and STS.
2026-02-28 | GSE273829 | GEO
Project description:An aerobic Lactobacillus plantarum culture displayed growth stagnation during early growth. Transcriptome analysis revealed that regain of growth after stagnation correlated with activation of CO2-producing pathways suggesting that limiting CO2-concentration induced stagnation. Analogously providing increased CO2 gas partial pressure during aerobic fermentation prevented the temporal growth stagnation. Keywords: cell type comparison
2008-01-18 | GSE10194 | GEO