Related Experiment Video
Updated: May 24, 2025
Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Short-chain fatty acids in multiple sclerosis: Associated with disability, number of T2 lesions, and inflammatory
Maria Inmaculada Dominguez-Mozo1, Daniel López-Mecández2, Luisa María Villar3
1Grupo de Investigación de Factores ambientales en enfermedades degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Española de Esclerosis Múltiple, Madrid, Spain.
Objective:
An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system.
Methods:
Multicentric observational retrospective cross-sectional study. In addition 161 pwMS and 130 HC were included. The following plasma SCFA were analyzed using liquid chromatography coupled to mass spectrometry: acetate (AA), propionate (PA) and butyrate (BA). Blood cell subpopulations and cytokine expression were analyzed by flow cytometry.
Results:
Plasma PA and PA/AA ratio was lower in pwMS than in HC (P = 0.0001, and P = 0.00005, respectively). PA/AA and BA/AA ratios were lower in pwMS with higher disability (P = 0.001, and P = 0.001, respectively). T2 lesion load inversely correlated with PA/AA (r = -0.353; P = 0.002) and BA/AA (r = -0.322; P = 0.005) ratios. Plasma PA/AA and/or BA/AA ratios negatively correlated with the following pro-inflammatory cytokines producing cells: GM-CSF+CD4+T, GM-CSF+CD8+T, TNF-alpha+CD4+T, TNF-alpha+CD8+T, IFN-gamma+CD4+T, IFN-gamma+CD8+T, and TNF-alpha+B cells.
Interpretation:
In MS, plasma PA/AA and BA/AA ratios are unbalanced, promoting an environment that could be boosting the mechanisms underlying the pathogenesis of the disease. Since we have found statistical significant associations with the EDSS and the number of T2 lesions, but not with the number of relapses or gadolinium enhancing lesions, PA/AA and BA/AA ratios could be more associated with those mechanisms of the disease related to the neurodegenerative processes than those related with the activity of the disease.
Insights
Short-chain fatty acids (SCFAs) like propionate (PA) and butyrate (BA) are altered in multiple sclerosis (MS) patients. Lower SCFA ratios correlate with increased disability and neurodegeneration markers in MS.
Area of Science:
- Neuroimmunology
- Microbiome research
- Metabolomics
Background:
- Alterations in gut microbiota composition are observed in multiple sclerosis (MS) patients compared to healthy controls (HC).
- Microorganism-derived metabolites, such as short-chain fatty acids (SCFAs), are implicated in MS pathogenesis.
- Understanding SCFA associations with disease parameters is crucial for MS research.
Purpose of the Study:
- To investigate the association between plasma SCFA levels and clinical/radiological parameters in MS.
- To explore the relationship between SCFAs and immune system inflammatory markers in MS patients.
- To analyze SCFA profiles in relation to disease severity and progression.
Main Methods:
- A multicentric observational retrospective cross-sectional study including 161 MS patients and 130 HC.
- Plasma SCFA (acetate, propionate, butyrate) were quantified using liquid chromatography-mass spectrometry.
- Blood cell subpopulations and cytokine expression were analyzed via flow cytometry.
Main Results:
- Lower plasma propionate (PA) and PA/acetate (AA) ratios were found in MS patients compared to HC.
- Reduced PA/AA and butyrate (BA)/AA ratios correlated with higher disability (EDSS) and T2 lesion load in MS patients.
- SCFA ratios negatively correlated with pro-inflammatory cytokine-producing immune cells (e.g., GM-CSF+, TNF-α+, IFN-γ+ T cells and TNF-α+ B cells).
Conclusions:
- Plasma PA/AA and BA/AA ratios are unbalanced in MS, potentially promoting disease pathogenesis.
- These SCFA ratios are significantly associated with EDSS and T2 lesion load, suggesting a link to neurodegenerative processes rather than active disease.
- Further research into SCFA modulation could offer novel therapeutic strategies for MS.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...