ArticlePLoS pathogens2021
Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Aging regulation by gut microbiota: molecular insights from Caenorhabditis elegans.Biogerontology · 2026Review
- Interplay between proteostasis pathways and innate immune responses inInfection and immunity · 2026Review
- MAPK/PMK-1 innate immune signaling protects the nematode Caenorhabditis elegans from increased intestinal colonization in an animal host-pathogen model in space.NPJ microgravity · 2026Article
- Caenorhabditis elegans as an experimental model for resilience-boosting microbiota interventions in nonmodel ectotherms.FEMS microbiology reviews · 2026Review
- The HDAC Inhibitor Butyrate Reduces SOD1 Aggregation and Improves Motor Function inInternational journal of cell biology · 2026Article
- Hedgehog-related genemicroPublication biology · 2026Article
- Neuroprotective Effects of Mushroom Biomass Digestive Fractions and Gut Microbiota Metabolites in Microglial andNutrients · 2025Article
- Effect of trypsin inhibitor isolated from tamarind seed (TTI) on caenorhabditis elegans survival under bacterial infection.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Exogenous prion-like proteins and their potential to trigger cognitive dysfunction.Molecular systems biology · 2025Article
- Caffeine-Induced Upregulation ofNutrients · 2024Article
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- Understanding the factors regulating host-microbiome interactions usingPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Multitier regulation of theJournal of bacteriology · 2024Article
- Feeding Drosophila gut microbiomes from young and old flies modifies the microbiome.Scientific reports · 2024Article
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- The gut microbiota modulate locomotion via vagus-dependent glucagon-like peptide-1 signaling.NPJ biofilms and microbiomes · 2024Article
- Gut Microbiota as a Modifier of Huntington's Disease Pathogenesis.Journal of Huntington's disease · 2024Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Protein conformational diseases are characterized by misfolding and toxic aggregation of metastable proteins, often culminating in neurodegeneration. Enteric bacteria influence the pathogenesis of neurodegenerative diseases; however, the complexity of the human microbiome hinders our understanding of how individual microbes influence these diseases. Disruption of host protein homeostasis, or proteostasis, affects the onset and progression of these diseases. To investigate the effect of bacteria on host proteostasis, we used Caenorhabditis elegans expressing tissue-specific polyglutamine reporters that detect changes in the protein folding environment. We found that colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad, while the presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity. Co-colonization with this butyrogenic strain suppressed bacteria-induced protein aggregation, emphasizing the importance of microbial interaction and its impact on host proteostasis. Further experiments demonstrated that the beneficial effect of butyrate depended on the bacteria that colonized the gut and that this protective effect required SKN-1/Nrf2 and DAF-16/FOXO transcription factors. We also found that bacteria-derived protein aggregates contribute to the observed disruption of host proteostasis. Together, these results reveal the significance of enteric infection and gut dysbiosis on the pathogenesis of protein conformational diseases and demonstrate the potential of using butyrate-producing microbes as a preventative and treatment strategy for neurodegenerative disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.