Experimental autoimmune encephalomyelitis is associated with changes of the microbiota composition in the gastrointestinal tract

Abstract

The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We collected fecal samples at key stages of EAE progression and quantified microbial abundances with 16S V3–V4 amplicon sequencing. Our analysis of the data suggests that the abundance of commensal Lactobacillaceae decreases during EAE while other commensal populations belonging to the Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae families expand. Community analysis with microbial co-occurrence networks points to these three expanding taxa as potential mediators of gut microbiome dysbiosis. We also employed PICRUSt2 to impute MetaCyc Enzyme Consortium (EC) pathway abundances from the original microbial abundance data. From this analysis, we found that a number of imputed EC pathways responsible for the production of immunomodulatory compounds appear to be enriched in mice undergoing EAE. Our analysis and interpretation of results provides a detailed picture of the changes to the gut microbiome that are occurring throughout the course of EAE disease progression and helps to evaluate EAE as a viable model for gut dysbiosis in MS patients.

Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity

“…The first found that commensal colonization with this microbe exacerbated EAE (102), fully consistent with our findings. The second found that continuous administration of a probiotic strain of L. reuteri suppressed EAE (103); the discordance with our study owing most likely to the mode of delivery and/or bacterial strain differences, as discussed above.…”

ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis

“…Namely, peptides originating from Lactobacillus reuteri mimic MOG, while Erysipelotrichaceae has been shown to act as an adjuvant to enhance the responses of encephalitogenic Th17 cells. Also, gut microbiota composition was shown to change during EAE and to vary between the disease stages and between different clinical subtypes of the disease (89)(90)(91). The contribution of gut dysbiosis to the CNS autoimmunity is shown in Figure 3, while the possibility to alter gut microbiota for the benefit of MS patients is discussed in Box 2.…”

“…Gut microbiota composition modulation by broad-spectrum antibiotics before EAE induction reduced the clinical severity of the disease (92)(93)(94), while the therapeutic application was inefficient (95). Still, EAE aggravation as the consequence of broad antibiotic application was observed in rats (89). Minocycline has been considered as a potential therapeutic for MS (96), and its effectiveness in the prevention of clinically isolated syndrome transition into definitive MS was evaluated in a clinical study (97).…”

The Nerves to Conduct a Multiple Sclerosis Crime Investigation

“…People moving from countries with a low prevalence of MS to those with a high prevalence adopt a higher risk of developing the disease [ 6 , 7 , 8 , 9 ], perhaps facilitated by changes in lifestyle and diet that drive a shift in the composition of the intestinal flora. People with MS [ 10 , 11 , 12 ] and animal models of the disease [ 13 ] have altered gut microbiota composition, which brings us to question whether the microbiome could be a driver of MS pathogenesis. There is an imminent need to better characterize changes in the microbiome composition of individuals living with MS and study the complex mechanisms by which microbiota can influence host biology and affect disease pathogenesis ( Box 1 ).…”