Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar 6;17(1):79.
doi: 10.1186/s12974-020-01766-9.

Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease

Clemens Gödel  1   2 , Birgit Kunkel  3 , Alireza Kashani  4 , Hans Lassmann  5 , Manimozhiyan Arumugam  3 , Gurumoorthy Krishnamoorthy  6
Affiliations

Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease

Clemens Gödel et al. J Neuroinflammation. .

Abstract

The gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.

Keywords: Antibiotics; CNS autoimmunity; EAE; Microbiota; Multiple sclerosis; microbiome.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Antibiotic treatment prevents spontaneous CNS autoimmune disease. a Schematic view of the treatment protocol. Significant increase in the cecum size following antibiotic treatment. Exemplary pictures are shown. b Bodyweight change in percent compared to the initial weight. n = 10 per group. c Incidence of spontaneous EAE in a cohort of antibiotic-treated OSE mice. n = 15 per group. *P < 0.05 (Gehan-Breslow-Wilcoxon test). d Frequencies of IL-17, IFNγ, IL-22, and TNF-α-producing CD4+CD45+cells in the small intestine from control and antibiotic-treated mice. n = 6–8 mice per group. *P < 0.05 (Mann-Whitney test). e Comparison of fecal microbiome alpha-diversities (Shannon index) of control and antibiotic-treated mice. f Comparison of fecal microbiome phylum compositions in control and antibiotic-treated mice. g Fold changes of significant OTUs identified by the Wilcoxon rank-sum test as differentially abundant in fecal microbiomes. OTUs are colored by phylum affiliation and grouped by the highest taxonomic resolution
Fig. 2
Fig. 2
Antibiotic treatment does not affect ongoing CNS autoimmune disease. a Bodyweight change in percent compared to the initial weight of EAE-affected OSE mice treated with antibiotics. n = 10 per group. b Mean cumulative score of EAE-affected OSE mice treated with antibiotics. n = 10 per group. c Mean clinical score of sick OSE mice treated with antibiotics. n = 10 per group. Quantification of the inflammatory score (d), demyelination score (e) of spinal cord, and demyelination score (f) of the optic nerve after 2 weeks of antibiotic treatment. n = 10 per group. g Mean clinical score of EAE-affected RR SJL/J mice treated with antibiotics. n = 6 per group
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kuntz TM, Gilbert JA. Introducing the microbiome into precision medicine. Trends Pharmacol Sci. 2016;38(1):81–91. doi: 10.1016/j.tips.2016.10.001. - DOI - PubMed
    1. Zmora N, Soffer E, Elinav E. Transforming medicine with the microbiome. Sci Transl Med. 2019;11(477):eaaw1815. doi: 10.1126/scitranslmed.aaw1815. - DOI - PubMed
    1. Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, Xia Z, Liu C, Klotz L, Stauffer U, Baranzini SE, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017;114(40):10719–10724. doi: 10.1073/pnas.1711233114. - DOI - PMC - PubMed
    1. Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–541. doi: 10.1038/nature10554. - DOI - PubMed
    1. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4615–4622. doi: 10.1073/pnas.1000082107. - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources