Short chain fatty acids levels in plasma of multiple sclerosis patients: a correlation with the disability of the disease and the activation of the immune system

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future.

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Short chain fatty acids (SCFA), the products of gut bacteria metabolism and their role in the host

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0011.6468 ◽

2018 ◽

Vol 72 ◽

pp. 131-142 ◽

Cited By ~ 7

Author(s):

Aleksandra Czajkowska ◽

Bogumiła Szponar

Keyword(s):

Fatty Acids ◽

Immune System ◽

Short Chain Fatty Acids ◽

Gastrointestinal Diseases ◽

Bacterial Consortium ◽

Treg Cells ◽

Short Chain ◽

Microbiome Composition ◽

Promising Tool ◽

Chain Fatty Acids

Gut bacterial consortium is essential for the homeostasis of the immune system in mammals. A significant role in maintaining this balance play short-chain fatty acids (SCFA), bacterial metabolites resulting from fermentation of dietary oligosaccharides. The most significant are butyric, propionic and acetic acids present in the microbiome in a specified mole ratio, but these proportions may change due to diet, age, diseases, and other factors. SCFA are the type of messengers between microbiota and immune system. They are responsible for maintaining the balance in the pro- and anti-inflammatory reaction through the set of free fatty acid receptors (GPR). Short chain fatty acids may induce regulatory T-cells (Treg) by an bakteinhibition of histone deacetylase enzyme; the biggest inhibitory potential has butyric acid, causing proliferation and an increase of the functional capabilities of Treg cells. Manipulation of the gut microbiome composition and SCFA level constitutes a promising tool supporting treatment of chronic gastrointestinal diseases associated with an inflammation or caused by dysbiosis due to intensive use of antibiotics.

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Short-chain fatty acids and gut microbiota in multiple sclerosis

Acta Neurologica Scandinavica ◽

10.1111/ane.13045 ◽

2018 ◽

Vol 139 (3) ◽

pp. 208-219 ◽

Cited By ~ 18

Author(s):

Pernille Melbye ◽

Anna Olsson ◽

Tue H. Hansen ◽

Helle B. Søndergaard ◽

Annette Bang Oturai

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis

Neurochemistry International ◽

10.1016/j.neuint.2019.104468 ◽

2019 ◽

Vol 129 ◽

pp. 104468 ◽

Cited By ~ 22

Author(s):

Qin Zeng ◽

Junli Gong ◽

Xiyuan Liu ◽

Chen Chen ◽

Xiaobo Sun ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Gut Dysbiosis ◽

Chinese Cohort ◽

Chain Fatty Acids

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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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Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs)

Acta Biochimica Polonica ◽

10.18388/abp.2018_2648 ◽

2019 ◽

Cited By ~ 30

Author(s):

Weronika Ratajczak ◽

Aleksandra Rył ◽

Arnold Mizerski ◽

Kinga Walczakiewicz ◽

Olimpia Sipak ◽

...

Keyword(s):

Fatty Acids ◽

Immune System ◽

Intestinal Microbiota ◽

Immune Cells ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Intestinal Microbiome ◽

16S Rrna Analysis ◽

Immunomodulatory Potential ◽

Chain Fatty Acids

Intestinal microbiota is an element of the bacterial ecosystem in all mammalian organisms. These microorganisms play a very important part in the development, functioning, and modulation of the immune system from the moment of birth. In recent years, owing to the use of modern sequencing techniques, the microbiome composition in healthy people has been identified based on bacterial 16S rRNA analysis. Currently, more and more attention is being given to the influence of microorganisms on the host’s cellular metabolism. Analysis of microbial metabolites, among them short-chain fatty acids (SCFAs), and disruption of intestinal microbiota homeostasis in terms of their effects on molecular regulatory mechanisms of immune reactions will surely improve the understanding of the etiology of many common diseases. SCFAs, mainly butyrate, propionate, and acetate, occur in specific amounts, and their proportions can change, depending on the diet, age and diseases. The levels of SCFAs are substantially influenced by the ratio of commensal intestinal bacteria, the disturbance of which (dysbiosis) can lead to a disproportion between the SCFAs produced. SCFAs are regarded as mediators in the communication between the intestinal microbiome and the immune system. The signal they produce is transferred, among others, in immune cells via free fatty acid receptors (FFARs), which belong to the family of G protein-coupled receptors (GPCRs). It has been also confirmed that SCFAs inhibit the activity of histone deacetylase (HDAC) – an enzyme involved in post-translational modifications, namely the process of deacetylation and, what is new, the process of histone crotonylation. These properties of SCFAs have an effect on their immunomodulatory potential i.e. maintaining the anti/pro-inflammatory balance. SCFAs act not only locally in the intestines colonized by commensal bacteria, but also influence the intestinal immune cells, and modulate immune response by multi-protein inflammasome complexes. SCFAs have been confirmed to contribute to the maintenance of the immune homeostasis of the urinary system (kidneys), respiratory system (lungs), central nervous system, and the sight organ.

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Review of short-chain fatty acids effects on the immune system and cancer

Food Bioscience ◽

10.1016/j.fbio.2020.100793 ◽

2020 ◽

Vol 38 ◽

pp. 100793 ◽

Cited By ~ 1

Author(s):

Yasin Fattahi ◽

Hamid Reza Heidari ◽

Ahmad Yari Khosroushahi

Keyword(s):

Fatty Acids ◽

Immune System ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-84881-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stephanie Trend ◽

Jonatan Leffler ◽

Anderson P. Jones ◽

Lilian Cha ◽

Shelley Gorman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

B Cells ◽

Immune Cells ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Bioactive Metabolites ◽

Healthy Controls ◽

Serum Factors ◽

Chain Fatty Acids

AbstractAltered 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.

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Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00625-0 ◽

2021 ◽

Author(s):

Chang H. Kim

Keyword(s):

Fatty Acids ◽

Immune System ◽

Cytotoxic T Cells ◽

Cell Types ◽

Short Chain Fatty Acids ◽

Lymphoid Cells ◽

Commensal Bacteria ◽

Short Chain ◽

Regulatory Functions ◽

Chain Fatty Acids

AbstractA mounting body of evidence indicates that dietary fiber (DF) metabolites produced by commensal bacteria play essential roles in balancing the immune system. DF, considered nonessential nutrients in the past, is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs. SCFAs act on many cell types to regulate a number of important biological processes, including host metabolism, intestinal functions, and immunity system. This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes. Current information regarding how SCFAs regulate innate lymphoid cells, T helper cells, cytotoxic T cells, and B cells and how these functions impact immunity, inflammation, and allergic responses are discussed.

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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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