Short-chain fatty acids and intestinal inflammation in multiple sclerosis: modulation of female susceptibility by microbial products?

Abstract Background Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal inflammation marker calprotectin are altered in MS. Methods 76 subjects (41 patients with relapsing–remitting MS and 35 age-matched controls) were investigated in this case–control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were compared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters. Results Median fecal calprotectin concentrations were within normal range in both groups without any group-specific differences. Fecal SCFA concentrations showed a non-significant reduction in MS patients compared to healthy subjects. Female subjects showed significantly reduced SCFA concentrations compared to male subjects. Conclusions In our cohort of MS patients, we found no evidence of an active intestinal inflammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.

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Short-chain fatty acids and intestinal inflammation in Multiple Sclerosis – Modulation of female susceptibility by microbial products?

10.21203/rs.3.rs-85998/v1 ◽

2020 ◽

Author(s):

Anouck Becker ◽

Mosab Abuazab ◽

Andreas Schwiertz ◽

Silke Walter ◽

Klaus C. Faßbender ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

Intestinal Inflammation ◽

Short Chain Fatty Acids ◽

Fecal Calprotectin ◽

Short Chain ◽

Therapeutic Regime ◽

Microbial Products ◽

Chain Fatty Acids

Abstract Background. Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data also suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFA) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we aimed to investigate whether SCFA and the fecal inflammation marker calprotectin are altered in MS. Methods. 76 subjects (41 patients with relapsing-remitting MS and 35 age-matched controls) were investigated in this case-control study. All subjects underwent clinical assessment with established scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentration. Fecal markers were compared between MS patients and controls, and were analyzed for an association with epidemiological as well as clinical parameters. Results. Median fecal calprotectin concentrations remained within normal range without any group-specific differences. Fecal SCFA showed a non-significant reduction in MS patients, whereas female subjects showed significantly reduced SCFA concentrations compared to male subjects. Conclusions. In our cohort of MS patients, we found no evidence of an active intestinal inflammation. As the vast majority of patients, however, was under immunotherapy, this might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFA in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.

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Fecal markers in Multiple Sclerosis Sex makes the difference

10.21203/rs.3.rs-41141/v1 ◽

2020 ◽

Author(s):

Anouck Becker ◽

Mosab Abuazab ◽

Andreas Schwiertz ◽

Silke Walter ◽

Klaus Faßbender ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Clinical Markers ◽

Control Subjects ◽

Fecal Markers ◽

Microbial Products ◽

Chain Fatty Acids

Abstract Background. Multiple Sclerosis (MS) is primarily considered as a neuro-inflammatory CNS disease. Yet, experimental data suggest a role for gut microbiota and microbial products like short chain fatty acids (SCFA) in the pathogenesis of MS. Very recently a high-ranked publication reported beneficial effects of propionate, a SCFA, in MS patients. Based on experimental and preliminary human data, we hypothesized that not only the gut microbiota but also microbial products and fecal inflammatory markers might be altered in MS.Methods. In a pilot study, we investigated fecal markers (short chain fatty acids, calprotectin) as well as clinical markers in patients with relapsing-remitting MS (RRMS) under different therapeutic regimes and compared the results to age-matched control subjects.Results. We observed a non-significant reduction in fecal SCFA in RRMS patients compared to control subjects. Fecal calprotectin concentrations did not differ significantly between MS patients and control subjects. We observed a significant reduction in fecal SCFA concentrations in women compared to men.Conclusions. We conclude that the observed sex-associated difference in fecal SCFA concentrations might be a contributing factor in the pathogenesis of MS, especially when taking into account the female predominance in MS. We suggest investigating the role of SCFA in MS in a longitudinal study (starting in drug-naïve patients) in larger cohorts of MS patients with defined therapeutic regimes. Such a study would allow to distinguish between drug effects and disease-immanent effects and might help to identify a potentially modifiable sex-associated contributing factor in MS.Trial registration. Registered by the local Ethics Committee (Reg.Nr. 81/18, Ethikkommission der Aerztekammer des Saarlandes, Saarbruecken, Germany).

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