Multiple sclerosis and the Gut Microbiome: Some Preclinical Results

The gut microbiome is measured by assessing the prokaryotic DNA of a stool sample, which reflects the various types of bacteria that are generally commensal, beneficial residents of our gut in the normal human.

In the past 10 years it has become apparent that our gut microbiome can be quite different between individuals based on diet and region, and that persons with many different diseases can have characteristic differences in their gut microbiome from the average normal gut microbiome.

One hypothesis regarding these differences is that the gut microbiome in disease states is not reflecting the effect of disease, but instead may be one of its causes, especially as some type of enabling or modulating cause of a pertubation of immunity in autoimmune disease.

How do we tell cause from effect in such a case? One method is to see if a transfer of microbiome between healthy and diseased makes a difference.The study below reports results of such transfers (but to mice from human with MS).

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ABSTRACT

in PNAS October 3, 2017 vol. 114 no. 40 10713-10718

Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models Egle Cekanaviciutea,1,2, Bryan B. Yoob,1, Tessel F. Runiaa,3, Justine W. Debeliusc, Sneha Singha, Charlotte A. Nelsona, Rachel Kannera, Yadira Bencosmed, Yun Kyung Leeb,4, Stephen L. Hausera, Elizabeth Crabtree-Hartmana, Ilana Katz Sandd, Mar Gaciasd, Yungjiao Zhud, Patrizia Casacciad,e, Bruce A. C. Creea, Rob Knightc, Sarkis K. Mazmanianb, and Sergio E. Baranzinia,5

Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved August 7, 2017 (received for review June 30, 2017)

Significance

We have experimentally investigated the immunoregulatory effects of human gut microbiota in multiple sclerosis (MS). We have identified specific bacteria that are associated with MS and demonstrated that these bacteria regulate T lymphocyte-mediated adaptive immune responses and contribute to the proinflammatory environment in vitro and in vivo. Thus, our results expand the knowledge of the microbial regulation of immunity and may provide a basis for the development of microbiome-based therapeutics in autoimmune diseases.

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.