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Bacterial Nanovesicles as Interkingdom Signaling Moieties Mediating Pain Hypersensitivity
Sameh Almousa1, Susy Kim1, Ashish Kumar1
1Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States.
ACS Nano
|January 17, 2025
Summary
Nanosized bacterial extracellular vesicles (bEVs) from gut dysbiosis induce pain hypersensitivity (allodynia) and systemic inflammation. These bEVs activate immune pathways via surface LPS, highlighting their role in disease.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Gut dysbiosis is linked to various pathologies, but mechanisms of microbiota influence on distant responses are unclear.
- Diet-induced obesity (DIO) models gut dysbiosis, offering a platform to study these mechanisms.
- Nanosized bacterial extracellular vesicles (bEVs) are potential mediators of gut-systemic communication.
Purpose of the Study:
- To investigate the role of bEVs in mediating allodynia in a DIO gut dysbiosis model.
- To determine the mechanisms by which bEVs influence pain sensitivity and inflammation.
Main Methods:
- bEVs were isolated from lean and DIO mice feces using ultracentrifugation and immunoprecipitation.
- bEVs were administered to wild-type and knockout mice to assess pain sensitivity and biodistribution.
- Immune cell responses, inflammation markers, and cellular uptake were analyzed using various assays.
Main Results:
- bEVs from DIO mice (bEVDIO) induced allodynia in wild-type mice, mimicking the DIO phenotype.
- The allodynia induced by bEVDIO was dependent on TRPA1/TRPV1 channels.
- bEVDIO entered circulation, caused systemic inflammation via LPS-TLR2/TLR4 pathways, and showed enhanced monocyte uptake.
Conclusions:
- bEVs are key mediators of allodynia and inflammation associated with gut dysbiosis.
- bEV surface components, particularly LPS, play a critical role in immune activation and pain signaling.
- This study reveals a novel mechanism linking gut dysbiosis to systemic pathologies through bacterial vesicles.
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