Abstract

Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a “Western Diet” (WD group; N = 10) for at least 12 months. Gut microbiota composition, analyzed by 16 S V4 rRNA gene sequencing and immunological profiles, was examined after a minimum of 12 months of diet. Results showed that, in the HV/LP diet group compared to the WD group: (1) Lachnospiraceae family was significantly more abundant; (2) IL-17-producing T CD4+ lymphocytes (p = 0.04) and PD-1 expressing T CD4+ lymphocytes (p = 0.0004) were significantly decreased; and (3) PD-L1 expressing monocytes (p = 0.009) were significantly increased. In the HV/LP diet group, positive correlations between Lachnospiraceae and both CD14+/IL-10+ and CD14+/TGFβ+monocytes (RSp = 0.707, p = 0.05, and RSp = 0.73, p = 0.04, respectively), as well as between Lachnospiraceae and CD4+/CD25+/FoxP3+ T lymphocytes (RSp = 0.68, p = 0.02) were observed. Evaluation of clinical parameters showed that in the HV/LP diet group alone the relapse rate during the 12 months follow-up period and the Expanded Disability Status Scale score at the end of the study period were significantly reduced. Diet modulates dysbiosis and improves clinical parameters in MS patients by increasing anti-inflammatory circuits. Because Lachnospiraceae favor Treg differentiation as well as TGFβ and IL-10 production this effect could be associated with an increase of these bacteria in the microbiota.

Highlights

  • Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and mediated by an auto-reactive immune process directed against central neural tissues

  • All filtered reads were classified at the Kingdom level, 93.08% of reads were classified at the family level, 54.78% of reads were classified at the genus level, 22.7% of reads were classified at the species level and 23.87% of reads were classified at the strain level

  • Diet plays an essential role in shaping the composition of the gut microbiome [35], and the gut microbiota modulates the status of the immune response [36]

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Summary

Introduction

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by demyelination and mediated by an auto-reactive immune process directed against central neural tissues. The use of a cocktail of antibiotics to alter the gut microbiota of mice prior to EAE induction was shown to result in a significant reduction of EAE severity This effect was mediated by an increase of CD4+/ CD25+/FoxP3+ regulatory T cells (Treg) cells [5] and of regulatory CD5+/B cells [6]. Results indicated that EAE-resistant germ-free mice are rendered susceptible to the disease by the introduction of segmented filamentous bacteria into their gut microbiome. This phenomenon was the consequence of an increased differentiation of proinflammatory Th17 cells [7]. A low-calorie diet was shown to have a beneficial effect in EAE [20], whereas a salt-rich diet resulted in an increased severity of EAE as a consequence of an upregulation of Th17 cell activity [21]

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