Antibiotics-Induced Intestinal Immunomodulation Attenuates Experimental Autoimmune Neuritis (EAN)
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Published:2024-05-31
Issue:1
Volume:19
Page:
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ISSN:1557-1904
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Container-title:Journal of Neuroimmune Pharmacology
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language:en
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Short-container-title:J Neuroimmune Pharmacol
Author:
Sprenger-Svačina Alina,Klein Ines,Svačina Martin K. R.,Bobylev Ilja,Kohle Felix,Schneider Christian,Schweitzer Finja,Piekarek Nadin,Barham Mohammed,Vehreschild Maria J. G. T.,Lehmann Helmar C.,Farowski Fedja
Abstract
Abstract
Background
The composition of gut microbiota plays a pivotal role in priming the immune system and thus impacts autoimmune diseases. Data on the effects of gut bacteria eradication via systemic antibiotics on immune neuropathies are currently lacking. This study therefore assessed the effects of antibiotics-induced gut microbiota alterations on the severity of experimental autoimmune neuritis (EAN), a rat model of Guillain-Barré Syndrome (GBS). Myelin P0 peptide 180–199 (P0 180–199)-induced EAN severity was compared between adult Lewis rats (12 weeks old) that received drinking water with or without antibiotics (colistin, metronidazole, vancomycin) and healthy rats, beginning antibiotics treatment immediately after immunization (day 0), and continuing treatment for 14 consecutive days. Neuropathy severity was assessed via a modified clinical score, and then related to gut microbiota alterations observed after fecal 16S rRNA gene sequencing at baseline and after EAN induction. Effectors of gut mucosal and endoneurial immunity were assessed via immunostaining. EAN rats showed increased gut mucosal permeability alongside increased mucosal CD8+ T cells compared to healthy controls. Antibiotics treatment alleviated clinical EAN severity and reduced endoneurial T cell infiltration, decreased gut mucosal CD8+ T cells and increased gut bacteria that may be associated with anti-inflammatory mechanisms, like Lactobacillus or Parasutterella. Our findings point out a relation between gut mucosal immunity and the pathogenesis of EAN, and indicate that antibiotics-induced intestinal immunomodulation might be a therapeutic approach to alleviate autoimmunity in immune neuropathies. Further studies are warranted to evaluate the clinical transferability of these findings to patients with GBS.
Graphical Abstract
Funder
Universitätsklinikum Köln
Publisher
Springer Science and Business Media LLC
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