The role of gut microbiota in shaping the relapse-remitting and chronic-progressive forms of multiple sclerosis in mouse models

Gandy, K. Alexa Orr; Zhang, Jiajia; Nagarkatti, Prakash; Nagarkatti, Mitzi

doi:10.1038/s41598-019-43356-7

Cited by 79 publications

(71 citation statements)

References 48 publications

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“…The effects of probiotics on the host immune system could be also mediated by a modulation of the gut microbiota; indeed, several studies reported alterations in bacterial taxonomical composition in stools from patients and from animal models (54,55), suggesting an important role of microbiota in (auto)immune diseases. To our knowledge, this is the first study that characterize the intestinal microbiota composition in the Lewis rat EAMG model, considering also the effect of a probiotic therapeutic treatment.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

et al. 2019

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Beneficial effects of probiotics on gut microbiota homeostasis and inflammatory immune responses suggested the investigation of their potential clinical efficacy in experimental models of autoimmune diseases. Indeed, administration of two bifidobacteria and lactobacilli probiotic strains prevented disease manifestations in the Lewis rat model of Myasthenia Gravis (EAMG). Here, we demonstrate the clinical efficacy of therapeutic administration of vital bifidobacteria (i.e., from EAMG onset). The mechanisms involved in immunomodulation were investigated with ex vivo and in vitro experiments. Improvement of EAMG symptoms was associated to decreased anti-rat AChR antibody levels, and differential expression of TGFβ and FoxP3 immunoregulatory transcripts in draining lymph nodes and spleen of treated-EAMG rats. Exposure of rat bone marrow-derived dendritic cells to bifidobacteria or lactobacilli strains upregulated toll-like receptor 2 mRNA expression, a key molecule involved in bacterium recognition via lipotheicoic acid. Live imaging experiments of AChR-specific effector T cells, co-cultured with BMDCs pre-exposed to bifidobacteria, demonstrated increased percentages of motile effector T cells, suggesting a hindered formation of TCR-peptide-MHC complex. Composition of gut microbiota was studied by 16S rRNA gene sequencing, and α and β diversity were determined in probiotic treated EAMG rats, with altered ratios between Tenericutes and Verrucomicrobia (phylum level), and Ruminococcaceae and Lachnospiraceae (family level). Moreover, the relative abundance of Akkermansia genus was found increased compared to healthy and probiotic treated EAMG rats. In conclusion, our findings confirms that the administration of vital bifidobacteria at EAMG onset has beneficial effects on disease progression; this study further supports preclinical research in human MG to evaluate probiotic efficacy as supplementary therapy in MG.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

et al. 2019

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“…Amongst others, the genus Parabacteroides was significantly more abundant in the gut microbiota of N+ responders compared to N+ non-responders . Notably, a recent study conducted in murine models of RMS and chronic-progressive MS identified Parabacteroides as more abundant in the gut microbiota of control mice [52]. Additionally, a previous study detected a significant reduction of Parabacteroides populations in the faecal microbiota of 71 MS patients not undergoing immunesuppressive treatment compared to that of 71 healthy control subjects [53].…”

Section: Gut Microbial Differences Between N+ Responders and N+ Non-rmentioning

confidence: 96%

Experimental infection with the hookworm, Necator americanus, promotes gut microbial diversity in human volunteers with relapsing multiple sclerosis

Jenkins

Pritchard

Tanasescu

et al. 2020

Preprint

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Background Helminth-associated changes in gut microbiota composition have been hypothesised to contribute to the immune-suppressive properties of parasitic worms. Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system whose pathophysiology has been recently linked to alterations of gut microbial communities. Results In the present study we investigated, for the first time, qualitative and quantitative changes in gut microbial composition of human volunteers with remitting multiple sclerosis (RMS) prior to and following experimental infection with the human hookworm, Necator americanus ( N+ ), and following anthelmintic treatment, and compared the findings with data obtained from a cohort of RMS patients subjected to placebo treatment ( PBO ). Bacterial 16S rRNA high-throughput sequencing data revealed significantly decreased microbial alpha diversity in the gut microbiota of PBO compared to N+ subjects over the course of the trial; additionally, we observed significant differences in the abundances of several bacterial taxa with putative immune-modulatory functions between study cohorts. Parabacteroides were significantly expanded in the gut microbiota of N + individuals for which no relapses were recorded at the end of the trial. Conclusions Overall, these data lend support to the hypothesis of a contributory role of parasite-associated alterations in gut microbial composition to the immunomodulatory properties of hookworm parasites.

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“…. A potential pro-inflammatory role has been proposed for this genus [40] what could be related to a reduced incidence of enteric disorders when feed restriction is applied.…”

Section: Administration Of Antibiotics Impact On Some Taxa Relative Amentioning

confidence: 99%

Housing conditions, level of feeding and presence of antibiotics in the feed shape rabbit cecal microbiota

Velasco-Galilea¹,

Guivernau²,

Piles³

et al. 2020

Preprint

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Background: the effect of the production environment and different management practices in rabbit cecal microbiota remains poorly understood. While previous studies have proved the impact of the age or the feed composition, research in the housing conditions and other animal management aspects, such as the presence of antibiotics in the feed or the level of feeding, is still needed. Characterization of microbial diversity and composition of growing rabbits raised under different conditions could help better understand the role these practices play in cecal microbial communities and how it may result in different animal performance.Results: four hundred twenty-five meat rabbits raised in two different facilities, fed under two feeding regimes (ad libitum or restricted) with feed supplemented or free of antibiotics, were selected for this study. A 16S rRNA gene-based assessment through the MiSeq Illumina sequencing platform was performed on cecal samples collected from these individuals at slaughter. Different univariate and multivariate approaches were conducted to unravel the influence of the different factors on microbial alpha diversity and composition at phylum, genus and OTU taxonomic levels. The animals raised in the facility harboring the most stable environmental conditions had greater, and less variable, microbial richness and diversity. Bootstrap univariate analyses of variance and sparse partial least squares-discriminant analyses endorsed that the farm exerted the largest influence on rabbit microbiota since the relative abundances of many taxa were found differentially represented between both facilities at all taxonomic levels characterized. Furthermore, only five OTUs were needed to achieve a perfect classification of samples according to the facility where animals were raised. The level of feeding and the presence of antibiotics did not modify the global alpha diversity but had an impact on some bacteria relative abundances, albeit in a small number of taxa compared with the farm, which is consistent with the lower sample classification power according to these factors achieved using microbial information.Conclusions: this study reveals different degrees of influence attributable to environment and animal management. It highlights the importance of offering a controlled breeding environment that reduces differences in microbial cecal composition that could be causative of different animal performance.

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The role of gut microbiota in shaping the relapse-remitting and chronic-progressive forms of multiple sclerosis in mouse models

Cited by 79 publications

References 48 publications

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

Experimental infection with the hookworm, Necator americanus, promotes gut microbial diversity in human volunteers with relapsing multiple sclerosis

Housing conditions, level of feeding and presence of antibiotics in the feed shape rabbit cecal microbiota

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