The lung microbiome regulates brain autoimmunity

Nature. 2022 Mar;603(7899):138-144. doi: 10.1038/s41586-022-04427-4. Epub 2022 Feb 23.


Lung infections and smoking are risk factors for multiple sclerosis, a T-cell-mediated autoimmune disease of the central nervous system1. In addition, the lung serves as a niche for the disease-inducing T cells for long-term survival and for maturation into migration-competent effector T cells2. Why the lung tissue in particular has such an important role in an autoimmune disease of the brain is not yet known. Here we detected a tight interconnection between the lung microbiota and the immune reactivity of the brain. A dysregulation in the lung microbiome significantly influenced the susceptibility of rats to developing autoimmune disease of the central nervous system. Shifting the microbiota towards lipopolysaccharide-enriched phyla by local treatment with neomycin induced a type-I-interferon-primed state in brain-resident microglial cells. Their responsiveness towards autoimmune-dominated stimulation by type II interferons was impaired, which led to decreased proinflammatory response, immune cell recruitment and clinical signs. Suppressing lipopolysaccharide-producing lung phyla with polymyxin B led to disease aggravation, whereas addition of lipopolysaccharide-enriched phyla or lipopolysaccharide recapitulated the neomycin effect. Our data demonstrate the existence of a lung-brain axis in which the pulmonary microbiome regulates the immune reactivity of the central nervous tissue and thereby influences its susceptibility to autoimmune disease development.

MeSH terms

  • Animals
  • Autoimmune Diseases
  • Autoimmunity*
  • Brain* / physiology
  • Lipopolysaccharides / pharmacology
  • Lung / microbiology
  • Microbiota*
  • Multiple Sclerosis* / etiology
  • Neomycin
  • Rats


  • Lipopolysaccharides
  • Neomycin