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

2019 ◽  
Vol 129 ◽  
pp. 104468 ◽  
Author(s):  
Qin Zeng ◽  
Junli Gong ◽  
Xiyuan Liu ◽  
Chen Chen ◽  
Xiaobo Sun ◽  
...  
2018 ◽  
Vol 139 (3) ◽  
pp. 208-219 ◽  
Author(s):  
Pernille Melbye ◽  
Anna Olsson ◽  
Tue H. Hansen ◽  
Helle B. Søndergaard ◽  
Annette Bang Oturai

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.


2018 ◽  
Vol 315 (5) ◽  
pp. G788-G798 ◽  
Author(s):  
Pekka Määttänen ◽  
Eberhard Lurz ◽  
Steven R. Botts ◽  
Richard Y. Wu ◽  
C. William Yeung ◽  
...  

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8–15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation. NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.


Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian-Mei Li ◽  
Rong Yu ◽  
Li-Ping Zhang ◽  
Shi-Yu Wen ◽  
Shui-Juan Wang ◽  
...  

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.


2021 ◽  
Vol 13 ◽  
Author(s):  
Ailin Luo ◽  
Shan Li ◽  
Xuan Wang ◽  
Zheng Xie ◽  
Shiyong Li ◽  
...  

Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.


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).


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 12 (1) ◽  
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 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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