In the recent years, gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are metabolites derived from microbial metabolism that could play a fundamental role in gut-brain axis. The most abundant SCFA are butyrate, propionate and acetate (more than 95%). There is a controversy with the role of these SCFA in relation to the immune system. While butyrate and propionate have anti-inflammatory properties, it has been proposed that acetate could be a pro-inflammatory metabolite. In a previous study of our group, acetate was found elevated in serum samples of MS patients in comparison with healthy controls.
To analyze the levels of acetate, propionate and butyrate in cerebrospinal fluid (CSF) and serum samples of patients with MS and other neurological diseases (OND).
Sixty-seven serum samples were collected (39 from MS patients, 30 at the time of clinically isolated syndrome [CIS] and 9 from patients with relapsing-remitting MS [RRMS], and 28 from patients with OND). For 41 of these patients we also had a CSF sample collected at the same time (31 from MS patients, 23 at the time of CIS and 8 from patients with RRMS, and 28 from patients with OND). We analyzed in these samples the levels of acetate, propionate and butyrate by liquid chromatography-mass spectrometry.
Serum acetate was significantly elevated in MS patients compared to OND patients (30.3 mM vs. 11.7 mM, respectively; p=0.002). Butyrate was significantly lower in the serum of MS patients (p = 0.026). Acetate / propionate and acetate / butyrate ratios were significantly elevated in serum samples of MS patients (p <0.0001, in both cases). We did not find significant differences between MS and OND when we analyzed the levels of acetate, butyrate and propionate in CSF samples.
In this study, acetate was found elevated in serum samples of MS patients in comparison to patients with OND. The ratios between acetate and propionate or butyrate (both anti-inflammatory metabolites), could help us to discriminate between MS patients and patients with OND. Larger cohorts are needed to study the possible relevance of SCFA in CSF samples.