scholarly journals Herpesvirus Antibodies, Vitamin D and Short-Chain Fatty Acids: Their Correlation with Cell Subsets in Multiple Sclerosis Patients and Healthy Controls

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 119
Author(s):  
Maria Inmaculada Dominguez-Mozo ◽  
Silvia Perez-Perez ◽  
Noelia Villarrubia ◽  
Lucienne Costa-Frossard ◽  
Jose Ignacio Fernandez-Velasco ◽  
...  

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.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie Trend ◽  
Jonatan Leffler ◽  
Anderson P. Jones ◽  
Lilian Cha ◽  
Shelley Gorman ◽  
...  

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.


2018 ◽  
Vol 139 (3) ◽  
pp. 208-219 ◽  
Author(s):  
Pernille Melbye ◽  
Anna Olsson ◽  
Tue H. Hansen ◽  
Helle B. Søndergaard ◽  
Annette Bang Oturai

2019 ◽  
Vol 129 ◽  
pp. 104468 ◽  
Author(s):  
Qin Zeng ◽  
Junli Gong ◽  
Xiyuan Liu ◽  
Chen Chen ◽  
Xiaobo Sun ◽  
...  

2020 ◽  
Author(s):  
Anouck Becker ◽  
Mosab Abuazab ◽  
Andreas Schwiertz ◽  
Silke Walter ◽  
Klaus C. Faßbender ◽  
...  

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.


2020 ◽  
Author(s):  
Anouck Becker ◽  
Mosab Abuazab ◽  
Andreas Schwiertz ◽  
Silke Walter ◽  
Klaus Faßbender ◽  
...  

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).


Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013225
Author(s):  
Szu-Ju Chen ◽  
Chieh-Chang Chen ◽  
Hsin-Yu Liao ◽  
Ya-Ting Lin ◽  
Yu-Wei Wu ◽  
...  

Background and Objectives:Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson’s disease (PD), but fecal levels of SCFAs in PD patients are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their inter-relationships with the PD disease process are scarce. We aimed to compare fecal and plasma levels of different SCFAs subtypes in PD patients and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD.Methods:A cohort of 96 PD patients and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical co-morbidities were evaluated, and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE).Results:Compared with controls, PD patients had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in PD patients. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of pro-inflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp. AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid.Discussion:Reductions in fecal SCFAs but increased plasma SCFAs were observed in PD patients and corelated to specific gut microbiota changes and the clinical severity of PD.Classification of evidence:This study provides Class III evidence that gut metabolite SCFAs distinguish between PD patients and controls, and are associated with disease severity in patients with PD.


CNS Oncology ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. CNS57 ◽  
Author(s):  
Antonio Dono ◽  
Anthony Patrizz ◽  
Ryan M McCormack ◽  
Nagireddy Putluri ◽  
Bhanu P Ganesh ◽  
...  

Aim: To explore fecal short-chain fatty acids and neurotransmitter alterations in a mouse–glioma model and glioma patients. Methods: Liquid chromatography–mass spectrometry and 16S rRNA-sequencing from fecal samples were performed to measure metabolite levels and taxa abundance in mice/humans. Mice underwent GL261 implantation with/without temozolomide. Glioma patients were compared with healthy controls. Results: Glioma altered several short-chain fatty acids and neurotransmitter levels. Reduced 5-hydroxyindoleaceic acid and norepinephrine levels were seen in mice and humans. Interestingly, temozolomide treatment abrogates the effects of glioma on fecal metabolites. Conclusion: Our findings demonstrate the interplay between glioma and the gut–brain axis. Further work is required to identify pathways within the gut–brain axis by which glioma influences and promotes the modulation of fecal metabolites and microbiome.


2021 ◽  
Author(s):  
Julio Madrigal-Matute ◽  
Sara Banon-Escandell

Colorectal cancer is one of the top contributors to the global burden of cancer incidence and mortality with genetic and environmental factors contributing to its etiology. Modifiable or environmental factors can be the cause of up to 60% of the risk of developing colorectal cancer. Hence, there is a growing interest in specifically defining what can be improved in our lifestyle to reduce this risk, improve the effectiveness of treatments, reduce side effects, and decrease the risk of recurrence. One of the elements directly related to lifestyle is gut microbiota. The microbial ecosystem has a vital role in colorectal cancer prevention and antitumoral response through modulation of the immune system and production of short-chain fatty acids. Numerous approaches have been used to identify healthy microbiota that can reduce the risk of cancer development, improve treatment efficacy, and reduce side effects. Scientific literature in this subject is growing exponentially and, therefore, systematic reviews and meta-analysis are required to ensure that appropriate recommendations are given to patients. This work aimed to perform a systematic analysis of the published literature to elucidate whether microbiota modulation through pre-, pro-, symbiotic treatment and/or nutritional intervention can be beneficial for patients diagnosed with colorectal cancer. Detailed analysis of published studies shows that some prebiotics, such as inulin and resistant starch, probiotics such as lactic strains producers of short-chain fatty acids, and consumption of unprocessed plant products, can be effective recommendations for patients diagnosed with colorectal cancer. This advice should always be individually tailored and followed up by a healthcare professional with expertise in the field.


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