Abstract
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.
Highlights
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS)
There were no associations between levels of any SCFA and the time since their magnetic resonance imaging (MRI) when presenting with Clinically Isolated Syndrome (CIS) or MS (n = 30, data not shown)
In this study of SCFAs in the serum of CIS/MS patients, propionate levels were significantly lower than those measured in the serum of healthy controls
Summary
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). Levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS. Abbreviations ARG Arginase BAFF B-cell activating factor CIS Clinically isolated syndrome DN Double negative (IgD−CD27−) GDF15 Growth differentiation factor 15 IDO Indoleamine 2,3-dioxygenase MBC Memory B-cells MFI Median fluorescence intensity MRI Magnetic resonance imaging MS Multiple sclerosis MZ Marginal zone SCFAs Short-chain fatty acids SD Standard deviation Sw MBC Class-switched memory B-cells Tfh T follicular helper. An investigation of the circulating levels of SCFAs provides one mechanism to investigate the collective and indirect effects of the microbiome on distal immune cells
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