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Molecular patterns from a human gut-derived Lactobacillus strain suppress pathogenic infiltration of leukocytes into the central nervous system

  • Sanchez, John Michael S.1
  • Doty, Daniel J.1
  • DePaula-Silva, Ana Beatriz1
  • Brown, D. Garrett1
  • Bell, Rickesha1
  • Klag, Kendra A.1
  • Truong, Amanda2
  • Libbey, Jane E.1
  • Round, June L.1
  • Fujinami, Robert S.1
  • 1 University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA , Salt Lake City (United States)
  • 2 Huntsman Cancer Institute, 2000 Circle of Hope, 2724 HCI-SOUTH, Salt Lake City, UT, 84112, USA , Salt Lake City (United States)
Published Article
Journal of Neuroinflammation
Springer (Biomed Central Ltd.)
Publication Date
Oct 06, 2020
DOI: 10.1186/s12974-020-01959-2
Springer Nature


BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating disease that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, the dense collection of microorganisms that colonize the gastrointestinal tract, plays a functional role in MS. Indeed, specific gut-resident bacteria are altered in patients with MS compared to healthy individuals, and colonization of gnotobiotic mice with MS-associated microbiota exacerbates preclinical models of MS. However, defining the molecular mechanisms by which gut commensals can remotely affect the neuroinflammatory process remains a critical gap in the field.MethodsWe utilized monophasic experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice and relapse-remitting EAE in SJL/J mice to test the effects of the products from a human gut-derived commensal strain of Lactobacillus paracasei (Lb).ResultsWe report that Lb can ameliorate preclinical murine models of MS with both prophylactic and therapeutic administrations. Lb ameliorates disease through a Toll-like receptor 2-dependent mechanism via its microbe-associated molecular patterns that can be detected in the systemic circulation, are sufficient to downregulate chemokine production, and can reduce immune cell infiltration into the central nervous system (CNS). In addition, alterations in the gut microbiota mediated by Lb-associated molecular patterns are sufficient to provide partial protection against neuroinflammatory diseases.ConclusionsLocal Lb modulation of the gut microbiota and the shedding of Lb-associated molecular patterns into the circulation may be important physiological signals to prevent aberrant peripheral immune cell infiltration into the CNS and have relevance to the development of new therapeutic strategies for MS.

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