Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis

Stanisavljević, Suzana; Lukić, Jovanka; Momčilović, Miljana; Miljković, Marija; Jevtić, Bojan; Kojić, Milan; Golić, Nataša; Stojković, M. Mostarica; Miljković, Djordje

doi:10.3920/bm2015.0159

Cited by 32 publications

(36 citation statements)

References 40 publications

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“…IFN-γ and IL-17 production were analyzed in parallel. The same pattern of IFN-γ and IL-17 production was observed as in our previous study (Stanisavljević et al, 2016). In order to get insight into IL-10 production relative to production of these major pro-inflammatory cytokines, ratios of IL-10 to IFN-γ and IL-17 were calculated for each sample.…”

Section: Resultssupporting

confidence: 89%

“…In addition, possible anti-inflammatory effects of Turicibacter were suggested (Presley et al, 2010; Werner et al, 2011; Suchodolski et al, 2012). In our previous study, when non-immunized AO and DA rats were compared, Turicibacter was detected only in feces of AO rats (Stanisavljević et al, 2016). In contrast to previous results, in this study Turicibacter sp.…”

Section: Discussionmentioning

confidence: 94%

“…Consequently, intensive CNS inflammation was observed in DA rats, but not in AO rats (reviewed in Momcilović et al, 2012). In our recent work, AO and DA rats have been compared for their GALT cellular composition and proinflammatory cytokine production as well as for their gut microbiota (Stanisavljević et al, 2016). Differences between the strains within the GALT, including lower percentage of CD4 + T cells and reduced generation of IL-17 and IFN-γ in MLN and PP of AO rats were determined (Stanisavljević et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…In our recent work, AO and DA rats have been compared for their GALT cellular composition and proinflammatory cytokine production as well as for their gut microbiota (Stanisavljević et al, 2016). Differences between the strains within the GALT, including lower percentage of CD4 + T cells and reduced generation of IL-17 and IFN-γ in MLN and PP of AO rats were determined (Stanisavljević et al, 2016). Microbial analyses of non-immunized animals have shown higher diversity of Lactobacillus spp.…”

Section: Introductionmentioning

confidence: 99%

“…in EAE-resistant AO rats comparing to DA rats. Moreover, an uncultivated species of Turicibacter genus was found to be exclusively present in feces of AO rats (Stanisavljević et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

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Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats

et al. 2016

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Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). It is widely accepted that autoimmune response against the antigens of the CNS is the essential pathogenic force in the disease. It has recently become increasingly appreciated that activated encephalitogenic cells tend to migrate toward gut associated lymphoid tissues (GALTs) and that interrupted balance between regulatory and inflammatory immunity within the GALT might have decisive role in the initiation and propagation of the CNS autoimmunity. Gut microbiota composition and function has the major impact on the balance in the GALT. Thus, our aim was to perform analyses of gut microbiota in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Albino Oxford (AO) rats that are highly resistant to EAE induction and Dark Agouti (DA) rats that develop EAE after mild immunization were compared for gut microbiota composition in different phases after EAE induction. Microbial analyses of the genus Lactobacillus and related lactic acid bacteria showed higher diversity of Lactobacillus spp. in EAE-resistant AO rats, while some members of Firmicutes and Proteobacteria (Undibacterium oligocarboniphilum) were detected only in feces of DA rats at the peak of the disease (between 13 and 16 days after induction). Interestingly, in contrast to our previous study where Turicibacter sp. was found exclusively in non-immunized AO, but not in DA rats, in this study it was detected in DA rats that remained healthy 16 days after induction, as well as in four of 12 DA rats at the peak of the disease. Similar observation was obtained for the members of Lachnospiraceae. Further, production of a typical regulatory cytokine interleukin-10 was compared in GALT cells of AO and DA rats, and higher production was observed in DA rats. Our data contribute to the idea that gut microbiota and GALT considerably influence multiple sclerosis pathogenesis.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats

et al. 2016

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CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice

et al. 2017

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Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Specifically, we showed that CD44 knockout (KO) mice were resistant to induction of EAE when compared to CD44wildtype (WT) mice and this was due to inhibition in the pro-inflammatory Th1/Th17 cells and increased induction of anti-inflammatory Th2/Treg cells. In the current study, we determined whether these effects resulted from an alteration in gut microbiota and the short-chain fatty acid (SCFA) production in CD44KO mice. Fecal transfer from naïve CD44KO but not CD44WT mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE. High-throughput bacterial 16S rRNA gene sequencing, followed by clustering sequences into operational taxonomic units (OTUs) and biochemical analysis, revealed that EAE-induced CD44KO mice showed significant diversity, richness, and evenness when compared to EAE-induced CD44WT mice at the phylum level, with dominant Bacteroidetes (68.5%) and low Firmicutes (26.8%). Further, data showed a significant change in the abundance of SCFAs, propionic acid and i-butyric acid in EAE-CD44KO compared to EAE-CD44WT mice. In conclusion, our results demonstrate that the attenuation of EAE seen following CD44 gene deletion in mice may result from alterations in the gut microbiota and SCFAs. Furthermore, our studies also demonstrate that the phenotype of gene knock-out animals may be shaped by gut microbiota.

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Microbiota and Diseases Associated with Rheumatic and Autoimmune Diseases

Henar

2024

Dysbiosis

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Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis

Cited by 32 publications

References 40 publications

Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats

Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats

CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice

Microbiota and Diseases Associated with Rheumatic and Autoimmune Diseases

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