scholarly journals Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces

2021 ◽  
Vol 11 ◽  
Author(s):  
Sundar Khadka ◽  
Seiichi Omura ◽  
Fumitaka Sato ◽  
Kazuto Nishio ◽  
Hideaki Kakeya ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Bacterial Species ◽  
Principal Component ◽  
High Serum ◽  
Free Form ◽  
Anatomical Site ◽  
Ileal Mucosa ◽  
The Central Nervous System ◽  
The Individual

We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose intravenous/intraperitoneal injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to alter the gut microbiota and immune responses, it is unclear whether the altered microbiota could be associated with inflammation in immune-mediated diseases, such as multiple sclerosis (MS). We aimed to determine whether CMG administration could affect the gut microbiota at three anatomical sites (feces, ileal contents, and the ileal mucosa), leading to suppression of inflammation in the central nervous system (CNS) in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE). We injected EAE mice with CMG, harvested the brains and spinal cords for histological analyses, and conducted microbiome analyses using 16S rRNA sequencing. CMG administration modulated EAE clinically and histologically, and altered overall microbiota compositions in feces and ileal contents, but not the ileal mucosa. Principal component analysis (PCA) of the microbiome showed that principal component (PC) 1 values in ileal contents, but not in feces, correlated with the clinical and histological EAE scores. On the other hand, when we analyzed the individual bacteria of the microbiota, the EAE scores correlated with significant increases in the relative abundance of two bacterial species at each anatomical site: Ruminococcus bromii and Blautia (Ruminococcus) gnavus in feces, Turicibacter sp. and Alistipes finegoldii in ileal contents, and Burkholderia spp. and Azoarcus spp. in the ileal mucosa. Therefore, CMG administration could alter the gut microbiota at the three different sites differentially in not only the overall gut microbiome compositions but also the abundance of individual bacteria, each of which was associated with modulation of neuroinflammation.

scholarly journals Gut Microbiota in Neurological Disorders

2019 ◽  
Vol 67 (6) ◽  
pp. 375-383 ◽  
Author(s):  
Marta Grochowska ◽  
Tomasz Laskus ◽  
Marek Radkowski
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Neurological Disorders ◽  
Bacterial Species ◽  
Human Intestine ◽  
Microbiota Composition ◽  
The World ◽  
The Central Nervous System ◽  
Development Course

Abstract The incidence of neurological disorders such as multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD) is increasing throughout the world, but their pathogenesis remains unclear and successful treatment remains elusive. Bidirectional communications between the central nervous system and gut microbiota may play some role in the pathogenesis of the above disorders. Up to a thousand bacterial species reside in human intestine; they colonize the gut shortly after birth and remain for life. Numerous studies point to the role of microbiota composition in the development, course and treatment of MS, AD and PD.

Cold-induced reactivity in multiple sclerosis patients

2017 ◽  
pp. 56-62 ◽  
Author(s):  
Л.И. Герасимова-Мейгал ◽  
И.М. Сиренев
Keyword(s):  
Multiple Sclerosis ◽  
Cold Test ◽  
Typical Feature ◽  
Humid Climate ◽  
Ssr Analysis ◽  
Epidemiological Surveys ◽  
The Central Nervous System ◽  
The Individual ◽  
Hands And Feet ◽  
Multiple Sclerosis Patients

Цель исследования - изучение особенностей восприимчивости пациентов с рассеянным склерозом (РС) к холодовому воздействию с помощью функциональных тестов, характеризующих функцию терморегуляции. Как известно, РС - хроническое прогрессирующее аутоиммунное заболевание центральной нервной системы мультифакториальной природы, более часто встречающееся в регионах с холодным и влажным климатом. Нарушения терморегуляции вследствие автономной дисфункции являются характерным признаком РС, вместе с тем участию холодового фактора в развитии заболевания не придается существенного значения. Методика. Обследовано 32 пациента (17 мужчин и 15 женщин, средний возраст 29,6 ± 4,2 года) с установленным диагнозом: РС ремиттирующе-рецидивирующая форма течения (средняя продолжительность заболевания - 4,2 ± 2,7 года) и 18 практически здоровых лиц группы сравнения. Восприятие холода оценивали с помощью визуально-аналоговой шкалы. Продолжительность холод-индуцированной вазоконстрикции после локального холодового теста изучали по данным инфракрасной термометрии. Вегетативную регуляцию вазомоторных реакций оценивали по результатам анализа вызванных кожных вегетативных потенциалов (ВКВП). Результаты. На основе анализа самооценки восприятия холода у пациентов с РС показана низкая переносимость холодового фактора. При проведении локального холодового теста отмечено замедление восстановления температуры кожи кисти, что характерно для усиления холод-индуцированной вазоконстрикции. В группе пациентов с РС выявлено снижение параметров ВКВП ладоней и стоп, свидетельствующее о дефиците нейрогенного контроля терморегуляционных сосудистых реакций. Заключение. У пациентов с РС выявлены нарушения механизмов терморегуляции при действии холода, что обусловливает высокую индивидуальную восприимчивость к холоду у данной категории лиц. Сопоставление результатов анализа механизмов индивидуальной холод-индуцированной реактивности у пациентов с РС с данными эпидемиологических исследований приводит к заключению о потенциальном модулирующем влиянии холодового фактора на течение РС. The purpose of the present study was focused on the evaluation of the sensitivity to cold in multiple sclerosis (MS) patients by means of functional thermoregulatory based tests. MS is known to be a chronic autoimmune progressive disease of the central nervous system of multifactor origin that is very common in regions with cold and humid climate. Disorder of thermoregulation caused by autonomic dysfunction is a typical feature of MS, however the role of the cold in the disease development is still underestimated. Methods. Thirty two MS patients (17 males, 15 females, mean age 29,6 ± 4,2 years) with the remittent form of the disease (mean disease duration 4,2 ± 2,7 years) and 18 age-matched healthy controls volunteered to participate in this study. Susceptibility to cold was analyzed with the use of visual-analogous scale. The duration of cold-induced vasoconstriction after local cold test was estimated using by infrared thermometry. Autonomic regulation of vasomotor reactions was investigated with the help of the skin sympathetic response (SSR) analysis. Results. The analysis of self-reported perception of the cold in MS patients showed their low tolerance to cold. Slow recovery of the skin temperature of the hand in the local cold test observed in MS patients was considered as the aggravated cold-induced vasoconstriction. The decreased SSR in the hands and feet in MS patients was found that indicates the deficit of the neurogenic control of thermoregulatory vasomotor reactions. Conclusion. The results obtained demonstrate the impairment of thermoregulation under cold in MS patients that leads to higher individual susceptibility to cold of this group. Comparing of the data found in this study on the mechanisms of the individual cold-induced reactivity in MS patients with epidemiological surveys enable to conclude that cold environment has potential modulating effect of on the course of MS.

scholarly journals The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials

2019 ◽  
Vol 28 (12) ◽  
pp. 1507-1527 ◽  
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
System A ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Review Reports

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing–remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.

scholarly journals Fair data for next-generation management of multiple sclerosis

2017 ◽  
Vol 24 (9) ◽  
pp. 1151-1156 ◽  
Author(s):  
Liesbet M Peeters
Keyword(s):  
Multiple Sclerosis ◽  
Multidisciplinary Treatment ◽  
Treatment Strategies ◽  
Population Based ◽  
Disease Modifying Drugs ◽  
Disease Epidemiology ◽  
Individual Level ◽  
Precision Level ◽  
The Central Nervous System ◽  
The Individual

Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the central nervous system with symptoms depending on the disease type and the site of lesions and is featured by heterogeneity of clinical expressions and responses to treatment strategies. An individualized clinical follow-up and multidisciplinary treatment is required. Transforming the population-based management of today into an individualized, personalized and precision-level management is a major goal in research. Indeed, a complex and unique interplay between genetic background and environmental exposure in each case likely determines clinical heterogeneity. To reach insights at the individual level, extensive amount of data are required. Many databases have been developed over the last few decades, but access to them is limited, and data are acquired in different ways and differences in definitions and indexing and software platforms preclude direct integration. Most existing (inter)national registers and IT platforms are strictly observational or focus on disease epidemiology or access to new disease modifying drugs. Here, a method to revolutionize management of MS to a personalized, individualized and precision level is outlined. The key to achieve this next level is FAIR data.

Biological markers in body fluids for activity and progression in multiple sclerosis

1999 ◽  
Vol 5 (4) ◽  
pp. 287-290
Author(s):  
Per Soelberg Sùrensen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Markers ◽  
Body Fluids ◽  
Therapeutic Effects ◽  
Therapeutic Decisions ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Relapsing Remitting Multiple Sclerosis

Reliable biological markers in body fluids for disease activity and progression are important for our understanding of the pathophysiology and therapeutic decisions in various subtypes of multiple sclerosis. Sampling from body fluids such as cerebrospinal fluid, blood, and urine constitutes the problem that the local immuno-inflammatory process takes place in the central nervous system whereas the disease activity is only to some extent reflected in the systemic immune compartment. Promising results have been obtained in studies of adhesion molecules, pro-inflammatory cytokines, co-stimulatory molecules and neopterin as markers of disease activity in relapsing-remitting multiple sclerosis. However, these results apply to groups of patients but not necessarily to individual patients. Currently no single body fluid marker is sufficiently correlated to disease activity to be used in the individual patient in monitoring disease activity, progression, or therapeutic effects.

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

2021 ◽  
Vol 19 ◽  
Author(s):  
Xu Wang ◽  
Zhen Liang ◽  
Shengnan Wang ◽  
Di Ma ◽  
Mingqin Zhu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Demyelinating Disease ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
Autoimmune Response ◽  
Therapeutic Implications ◽  
The Central Nervous System ◽  
Underlying Mechanisms

: The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study (Preprint)

2019 ◽  
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

BACKGROUND Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. OBJECTIVE Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. METHODS This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. RESULTS Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. CONCLUSIONS The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16162

The mechanism of action of methylprednisolone in the treatment of multiple sclerosis

2005 ◽  
Vol 11 (4) ◽  
pp. 425-432 ◽  
Author(s):  
J S Sloka ◽  
M Stefanelli
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Current Treatment ◽  
Necrosis Factor Alpha ◽  
Cytotoxic Effects ◽  
Treatment Regimes ◽  
The Central Nervous System ◽  
Factor Alpha ◽  
Cytokine Cascade ◽  
The Individual

Methylprednisolone plays an important role in the current treatment of multiple sclerosis (MS), particularly in the acute phase of relapse. It acts in various ways to decrease the inflammatory cycle including: dampening the inflammatory cytokine cascade, inhibiting the activation of T cells, decreasing the extravasation of immune cells into the central nervous system, facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha. This paper reviews the most recent observations on these mechanisms both to understand the disease mechanism and its treatment. As more becomes known about these mechanisms, it may become possible to design treatment regimes that are more specific towards both the individual and the disease state.

scholarly journals COMPARATIVE ANALYSIS OF THE RESULTS RECEIVED IN THE PAIN EFFECTS SCALE IN WOMEN WITH MULTIPLE SCULPROSIS

2018 ◽  
Vol 28 (2) ◽  
pp. 519-523
Author(s):  
Inna Mincheva Ivanova
Keyword(s):  
Multiple Sclerosis ◽  
Statistical Significance ◽  
Pain Syndrome ◽  
Chronic Fatigue ◽  
The Body ◽  
Final Study ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
The Individual ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS), one of the biggest puzzles in medicine. A number of drugs and therapies have been developed that affect the symptoms or change the severity and frequency of the seizures. Multiple sclerosis is of great social and economic importance to the world, due to the great invasion at early age. It affects the "young adults" in their creatively active period - between 10 and 50 years of age. Contrary to most allegations that pain is absent in MS patients, this is not the case. In the first periods of the disease, pain is almost absent, apart from the periodic manifestation of cramps, perceptions and all types of pain in the body, which at night interfere with sleep, provoke chronic fatigue and irritability (as they themselves have other mechanisms leading to the event their). However, some studies show that pain persists more frequently in women than in men. In most cases, disabling and immobilizing patients is exalted by their attempts to avoid pain. Physiotherapy is a basic tool for maintaining and improving the general condition of the patient. The study involved 22 patients with relapsing-remitting MS. The survey was conducted on the territory of Sofia - NSA "Vasil Levski", in the period from 01.09.2013 to 30.10.2015. The pain syndrome was evaluated in multiple sclerosis patients, at the beginning, the 10th procedure and the last procedure. For each patient in the experimental group, 20 procedures were performed within 10 weeks. The duration of the individual activity was 1 hour. The procedures for hippotherapy were a total of 16, each lasting 30 minutes. After the completion of the 10-week Physiotherapy program, each of the patients continues the hippotherapy courses on the Khan Asparuh horse base. The therapeutic program we have prepared and tested includes the following: Exercise with a large therapeutic ball (fitball); proprioceptive neuromuscular facilitation (PNF); myofascial techniques (MFT); autogenous training (AT); hippo therapy (HT). During the study, the subsequent results showed a significant decrease in pain in the tested group. At the end of the study, the improvement of the indicators from the initial to the final study were seen. The statistical significance is less than or equal to 0.01, with the possibility of error being minimal. From the conclusions, it can be said that the methodology thus performed brings great positives in terms of pain reduction in women with multiple sclerosis who participated in the study.

scholarly journals Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study

10.2196/16162 ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. e16162
Author(s):  
Jeske van Pamelen ◽  
Lynn van Olst ◽  
Andries E Budding ◽  
Helga E de Vries ◽  
Leo H Visser ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Disease Onset ◽  
Oral Microbiota ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Moment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Brain

Background Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. Objective Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. Methods This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. Results Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. Conclusions The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16162

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