GEO accession GSE252555 is currently private and is scheduled to be released on Dec 31, 2025.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1061165 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gnotobiotic mice were mono-colonized with either the wild-type Clostridioides difficile ATCC 43255 strain or the proline reductase mutant (ΔprdB) of the ATCC 43255 strain. Cecal contents were collected and underwent RNASeq at the timepoints indicated below for pathway enrichment and transcritpmic analyses. Metatranscriptomic sequence processing was carried out as in Girinathan, et al, 2021 (PMID: 34637781)
2026-06-09 | GSE252555 | GEO
Project description:C. difficile's proline reductase harnesses host and commensal factors to drive efficient metabolism and progression to disease. Commensal plus C. difficile.
| PRJNA1064116 | ENA
Project description:Gnotobiotic mice were colonized with Clostridium sardiniense DSM 599 7 days prior to infection with 10^3 spores of wild-type Clostridioides difficile ATCC 43255 or the proline reductase (ΔprdB) mutant of ATCC43255 strain. Cecal contents were collected and underwent RNASeq at the timepoints indicated below for pathway enrichment and transcritpmic analyses. Metatranscriptomic sequence processing was carried out as in Girinathan, et al, 2021 (PMID: 34637781)
2026-06-09 | GSE253149 | GEO
Project description:Clostridium difficile, a proteolytic Gram-positive anaerobe, has emerged as a significant nosocomial pathogen. Stickland fermentation reactions are thought to be important for growth of C. difficile. In Stickland reactions, pairs of amino acids donate and accept electrons, generating ATP and reducing power in the process. Reduction of the electron acceptors proline and glycine requires the D-proline reductase (PR) and the glycine reductase (GR) enzyme complexes, respectively. PrdR, a sigma54-dependent regulator, activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoding genes, suggesting that PrdR is a central metabolism regulator that controls preferential utilization of proline and glycine to produce energy via the Stickland reactions. Here, transcriptional profiling of C. difficile comparing growth in TY medium supplemented with 30 mM L-proline to growth in TY medium alone is performed.
2015-10-01 | GSE42469 | GEO
Project description:Clostridium difficile, a proteolytic Gram-positive anaerobe, has emerged as a significant nosocomial pathogen. Stickland fermentation reactions are thought to be important for growth of C. difficile. In Stickland reactions, pairs of amino acids donate and accept electrons, generating ATP and reducing power in the process. Reduction of the electron acceptors proline and glycine requires the D-proline reductase (PR) and the glycine reductase (GR) enzyme complexes, respectively. PrdR, a sigma54-dependent regulator, activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoding genes, suggesting that PrdR is a central metabolism regulator that controls preferential utilization of proline and glycine to produce energy via the Stickland reactions. Here, transcriptional profiling of the C. difficile 630E strain vs. a prdR mutant (LB-CD8) after 4h of growth in the presence of proline is performed.
2015-10-01 | GSE42471 | GEO
Project description:The microbiota produces thousands of potentially bioactive small molecules1-3. High-throughput bioactivity screens of in vitro commensal cultures have exposed microbiota metabolites that shape host physiology by activating diverse G protein-coupled receptors (GPCR)4-7. However, due to technical limitations, the GPCRome-wide bioactivities of in vivo metabolomes, which result from complex diet-microbe-host interactions, remain unexplored. Here we leveraged a novel multiplexed GPCR screening technology to assess GPCRome-wide bioactivities of 100 commensal strains grown in vivo in mono-associated germ-free mice or in vitro in bacterial culture media. In vivo and in vitro commensal metabolomes exhibited distinct GPCR activation patterns due to: 1) host-mediated metabolite degradation, 2) in vivo microbial metabolic reprogramming, and 3) biotransformation of dietary substrates. Notably, we identified multiple commensal strains that produced acetylcholine (ACh) in vivo via the conversion of dietary choline, including select Bifidobacteria strains that dominate the microbiome in early life and a probiotic Pediococcus strain. Mechanistically, we identified and characterized the bacterial enzymes mediating this biotransformation in Bifidobacterium breve and Pediococcus pentosaceus, and generated an isogenic mutant B. breve strain lacking ACh production. Mice colonized with an ACh-producing B. breve strain and treated with an FDA-approved acetylcholinesterase inhibitor exhibited enhanced intestinal immunoglobulin A (IgA) production, altered microbiota composition, and increased resistance to enteric infection. Together, these findings suggest that commensal-derived ACh can enhance intestinal IgA production, strengthen mucosal immune defenses, and reinforce host-microbiota mutualism.
2026-05-29 | GSE326448 | GEO
Project description:The microbiota produces thousands of potentially bioactive small molecules1-3. High-throughput bioactivity screens of in vitro commensal cultures have exposed microbiota metabolites that shape host physiology by activating diverse G protein-coupled receptors (GPCR)4-7. However, due to technical limitations, the GPCRome-wide bioactivities of in vivo metabolomes, which result from complex diet-microbe-host interactions, remain unexplored. Here we leveraged a novel multiplexed GPCR screening technology to assess GPCRome-wide bioactivities of 100 commensal strains grown in vivo in mono-associated germ-free mice or in vitro in bacterial culture media. In vivo and in vitro commensal metabolomes exhibited distinct GPCR activation patterns due to: 1) host-mediated metabolite degradation, 2) in vivo microbial metabolic reprogramming, and 3) biotransformation of dietary substrates. Notably, we identified multiple commensal strains that produced acetylcholine (ACh) in vivo via the conversion of dietary choline, including select Bifidobacteria strains that dominate the microbiome in early life and a probiotic Pediococcus strain. Mechanistically, we identified and characterized the bacterial enzymes mediating this biotransformation in Bifidobacterium breve and Pediococcus pentosaceus, and generated an isogenic mutant B. breve strain lacking ACh production. Mice colonized with an ACh-producing B. breve strain and treated with an FDA-approved acetylcholinesterase inhibitor exhibited enhanced intestinal immunoglobulin A (IgA) production, altered microbiota composition, and increased resistance to enteric infection. Together, these findings suggest that commensal-derived ACh can enhance intestinal IgA production, strengthen mucosal immune defenses, and reinforce host-microbiota mutualism.
2026-05-29 | GSE326301 | GEO
Project description:The microbiota produces thousands of potentially bioactive small molecules1-3. High-throughput bioactivity screens of in vitro commensal cultures have exposed microbiota metabolites that shape host physiology by activating diverse G protein-coupled receptors (GPCR)4-7. However, due to technical limitations, the GPCRome-wide bioactivities of in vivo metabolomes, which result from complex diet-microbe-host interactions, remain unexplored. Here we leveraged a novel multiplexed GPCR screening technology to assess GPCRome-wide bioactivities of 100 commensal strains grown in vivo in mono-associated germ-free mice or in vitro in bacterial culture media. In vivo and in vitro commensal metabolomes exhibited distinct GPCR activation patterns due to: 1) host-mediated metabolite degradation, 2) in vivo microbial metabolic reprogramming, and 3) biotransformation of dietary substrates. Notably, we identified multiple commensal strains that produced acetylcholine (ACh) in vivo via the conversion of dietary choline, including select Bifidobacteria strains that dominate the microbiome in early life and a probiotic Pediococcus strain. Mechanistically, we identified and characterized the bacterial enzymes mediating this biotransformation in Bifidobacterium breve and Pediococcus pentosaceus, and generated an isogenic mutant B. breve strain lacking ACh production. Mice colonized with an ACh-producing B. breve strain and treated with an FDA-approved acetylcholinesterase inhibitor exhibited enhanced intestinal immunoglobulin A (IgA) production, altered microbiota composition, and increased resistance to enteric infection. Together, these findings suggest that commensal-derived ACh can enhance intestinal IgA production, strengthen mucosal immune defenses, and reinforce host-microbiota mutualism.
2026-05-29 | GSE326271 | GEO
Project description:The microbiota produces thousands of potentially bioactive small molecules1-3. High-throughput bioactivity screens of in vitro commensal cultures have exposed microbiota metabolites that shape host physiology by activating diverse G protein-coupled receptors (GPCR)4-7. However, due to technical limitations, the GPCRome-wide bioactivities of in vivo metabolomes, which result from complex diet-microbe-host interactions, remain unexplored. Here we leveraged a novel multiplexed GPCR screening technology to assess GPCRome-wide bioactivities of 100 commensal strains grown in vivo in mono-associated germ-free mice or in vitro in bacterial culture media. In vivo and in vitro commensal metabolomes exhibited distinct GPCR activation patterns due to: 1) host-mediated metabolite degradation, 2) in vivo microbial metabolic reprogramming, and 3) biotransformation of dietary substrates. Notably, we identified multiple commensal strains that produced acetylcholine (ACh) in vivo via the conversion of dietary choline, including select Bifidobacteria strains that dominate the microbiome in early life and a probiotic Pediococcus strain. Mechanistically, we identified and characterized the bacterial enzymes mediating this biotransformation in Bifidobacterium breve and Pediococcus pentosaceus, and generated an isogenic mutant B. breve strain lacking ACh production. Mice colonized with an ACh-producing B. breve strain and treated with an FDA-approved acetylcholinesterase inhibitor exhibited enhanced intestinal immunoglobulin A (IgA) production, altered microbiota composition, and increased resistance to enteric infection. Together, these findings suggest that commensal-derived ACh can enhance intestinal IgA production, strengthen mucosal immune defenses, and reinforce host-microbiota mutualism.
2026-05-29 | GSE326286 | GEO
Project description:The microbiota produces thousands of potentially bioactive small molecules1-3. High-throughput bioactivity screens of in vitro commensal cultures have exposed microbiota metabolites that shape host physiology by activating diverse G protein-coupled receptors (GPCR)4-7. However, due to technical limitations, the GPCRome-wide bioactivities of in vivo metabolomes, which result from complex diet-microbe-host interactions, remain unexplored. Here we leveraged a novel multiplexed GPCR screening technology to assess GPCRome-wide bioactivities of 100 commensal strains grown in vivo in mono-associated germ-free mice or in vitro in bacterial culture media. In vivo and in vitro commensal metabolomes exhibited distinct GPCR activation patterns due to: 1) host-mediated metabolite degradation, 2) in vivo microbial metabolic reprogramming, and 3) biotransformation of dietary substrates. Notably, we identified multiple commensal strains that produced acetylcholine (ACh) in vivo via the conversion of dietary choline, including select Bifidobacteria strains that dominate the microbiome in early life and a probiotic Pediococcus strain. Mechanistically, we identified and characterized the bacterial enzymes mediating this biotransformation in Bifidobacterium breve and Pediococcus pentosaceus, and generated an isogenic mutant B. breve strain lacking ACh production. Mice colonized with an ACh-producing B. breve strain and treated with an FDA-approved acetylcholinesterase inhibitor exhibited enhanced intestinal immunoglobulin A (IgA) production, altered microbiota composition, and increased resistance to enteric infection. Together, these findings suggest that commensal-derived ACh can enhance intestinal IgA production, strengthen mucosal immune defenses, and reinforce host-microbiota mutualism.
2026-05-29 | GSE326280 | GEO