Tag: multiple sclerosis

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Autoimmune Disorders Now Affect Roughly One in Ten Individuals

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A population-based study of 22 million people in the UK estimates that around one in ten individuals in the UK now live with an autoimmune disorder. The findings, published in The Lancet, also highlight important socioeconomic, seasonal and regional differences for several autoimmune disorders, providing new clues as to what factors may be involved in these conditions.

There are more than 80 known autoimmune diseases, including conditions like rheumatoid arthritis, type 1 diabetes and multiple sclerosis, some of which have been increasing in the last few decades.

This has raised the question whether overall incidence of autoimmune disorders is on the rise and what factors are involved, such as environmental factors or behavioural changes in society. The exact causes of autoimmune diseases remain largely unknown, including how much can be attributed to a genetic predisposition to disease and how much is down to exposure to environmental factors.

The study used anonymised electronic health data from 22 million individuals in the UK to investigate 19 of the most common autoimmune diseases. The authors examined whether incidence of autoimmune diseases is rising over time, who is most affected by these conditions and how different autoimmune diseases may co-exist with each other.

They found that the 19 autoimmune diseases studied affect around 10% of the population. This is higher than previous estimates, which ranged from 3–9% and often relied on smaller sample sizes and included fewer autoimmune conditions. The analysis also highlighted a higher incidence in women (13%) than men (7%).

The research discovered evidence of socioeconomic, seasonal and regional disparities for several autoimmune disorders, suggesting that these conditions are unlikely to be caused by genetic differences alone. This observation may point to the involvement of potentially modifiable risk factors such as smoking, obesity or stress. It was also found that in some cases a person with one autoimmune disease is more likely to develop a second, compared to someone without an autoimmune disease.

Dr Nathalie Conrad at the University of Oxford said: “We observed that some autoimmune diseases tended to co-occur with one another more commonly than would be expected by chance or increased surveillance alone. This could mean that some autoimmune diseases share common risk factors, such as genetic predispositions or environmental triggers. This was particularly visible among rheumatic diseases and among endocrine diseases. But this phenomenon was not generalised across all autoimmune diseases. Multiple sclerosis, for example, stood out as having low rates of co-occurrence with other autoimmune diseases, suggesting a distinct pathophysiology.”

These findings reveal novel patterns that will inform the design of further research into the possible common causes of different autoimmune diseases.

Professor Geraldine Cambridge at UCL Medicine said: “Our study highlights the considerable burden that autoimmune diseases place upon individuals and the wider population. Disentangling the commonalities and differences within this large and varied set of conditions is a complex task. There is a crucial need, therefore, to increase research efforts aimed at understanding the underlying causes of these conditions, which will support the development of targeted interventions to reduce the contribution of environmental and social risk factors.”

Source: University College London

Categories : Diseases, Syndromes and ConditionsTags :

Light Therapy Relieves MS Fatigue Symptoms

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Multiple Sclerosis (MS) is almost always accompanied by fatigue, a massive tiredness that is described by the vast majority of patients as the most distressing symptom. Researchers have now identified light therapy as a promising nonpharmaceutical treatment option: patients included in the study showed a measurable improvement after just 14 days of use. Their study’s results were published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

The research team led by Stefan Seidel from the Department of Neurology at MedUni Vienna and AKH Vienna, relied not only on surveys but also on objective measurements when selecting the test persons – the first study of its kind to do so. For example, sleep-wake disorders were ruled out in the 26 participating MS patients, particularly with the assistance of various sleep medicine examinations. “In this manner, for example, we ensured that MS patients with fatigue do not suffer from sleep apnoea or periodic leg movements during sleep. Both are sleep disorders that can lead to fatigue in everyday life,” elaborated study leader Stefan Seidel.

Performance improvement

The test persons – all patients of the Neurology Department at MedUni Vienna and AKH Vienna – were equipped with commercially available light sources for self-testing at home: Half of the participants received a daylight lamp with a brightness of 10 000 lux (equivalent not to a cloudy day but not direct sunlight), while the other half received an identical lamp that emitted a red light with an intensity of <300 lux due to a filter (about the intensity of an office working environment). While the red light used by the control group showed no effect, the researchers were able to observe measurable successes in the other group after only 14 days: The participants who used their 10 000 lux daylight lamp for half an hour every day showed improved physical and mental performance after only a short period of time. In addition, the group of participants who had consumed bright light displayed less daytime sleepiness in comparison with the other group.

A nonpharmaceutical approach

Fatigue is a severe form of tiredness and fatigability that occurs in 75 to 99 percent of people with MS and is described as particularly distressing. Nerve damage triggered by MS is one possible cause. In addition to behavioural measures, such as regular rest breaks, various medications are currently available to alleviate fatigue, but some of these are associated with severe side effects. “The findings from our study represent a promising non-drug therapeutic approach,” Stefan Seidel said. However, the results still need to be confirmed in a subsequent larger-scale study. The reinvigorating mechanism of light therapy on MS patients will also be the subject of further scientific research.

Source: Medical University of Vienna

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Scientists Uncover Three Genes Linked to Multiple Sclerosis

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Genetics
Image source: Pixabay

New research published in the Annals of Clinical and Translational Neurology has identified three genes and their expressed proteins that may be involved in the pathogenesis of multiple sclerosis.

By comparing information on the genes and proteins expressed in the brains of thousands of individuals with and without multiple sclerosis, investigators discovered different expression levels of the SHMT1, FAM120B, and ICA1L genes (and their proteins) in brain tissues of patients versus controls.

Protein abundance alteration in human brain has linked to MS. For instance, protein abundance of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP)3 and thymosin β-46 was dysregulated in lesions from MS patients’ brain, and these proteins have been used for disease severity prediction and targeted therapy lately. In addition, compared to bodily fluid samples like cerebrospinal fluid and plasma, human brain tissue directly reflects the pathophysiology changes of MS and has become increasingly important in disease biomarker identification. However, few studies focused on specific subregions of the brain, ignoring the possible differences in protein types and abundance between subregions with distinct functions.

Studying the functions of these genes may uncover new information on the mechanisms involved in the development and progression of multiple sclerosis. “Our findings shed new light on the pathogenesis of MS and prioritised promising targets for future therapy research,” the authors wrote.

Source: Wiley

Categories : Metabolic DisordersTags :

Anti-hyperglycaemic Drugs Raise or Lower MS Risk Depending on Age

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A new study published in the journal Heliyon found that people older than 45 whose Type 2 diabetes (T2D) was treated with anti-hyperglycaemic drugs had an increased risk of multiple sclerosis (MS), especially women, while the reverse was true in under 45s.

“Our findings reinforce the need for a precision medicine approach to preventing MS in these vulnerable populations,” said lead researcher Kathleen Rodgers, PhD, associate director of translational neuroscience at the Center for Innovation in Brain Science.

Multiple sclerosis (MS) is an unpredictable autoimmune neurological disorder that affects the central nervous system and leads to severe physical and cognitive disability. It is estimated that more than 2.8 million worldwide are living with MS.

For people with T2D, growing evidence links metabolic disorders and MS through a common driver of increased autoimmunity. This brings into question the impact of anti-hyperglycaemic therapeutics used to treat T2D, including insulin, on the incidence of MS.

“Previous research has shown a neuroprotective effect of anti-hyperglycaemic medications in Alzheimer’s disease and other related dementias,” Dr Rodgers said. “For MS, we wanted to further examine age and sex differences, particularly among men and women under 45 with Type 2 diabetes.”

They found that men older than 45 years old had a slightly significant increase of MS risk and women older than 45 years exhibited a significant increase in MS incidence after anti-hyperglycaemic exposure. In addition to age differences, the risk analysis by drug class showed that exposure to insulin in patients older than 45 years old was associated with a greater increased risk compared with other therapies.

In patients younger than 45, anti-hyperglycaemic exposure was protective against the development of MS.

The study drew on a US-based insurance claims database of 151 million participants to identify more than 5 million patients with a diagnosis of T2D and either early-onset or late-onset MS. Researchers segmented the data by age – T2D diagnosis before or after age 45 – and sex to decode the factors driving MS risk in both populations, especially in women over 45 years of age.

Source: University of Arizona Health Sciences

Categories : Diet and NutritionTags :

Guar Gum Limits Inflammation and Delays MS-like Symptoms

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Guar gum is a common additive in foods such as gummy sweets, but a healthier alternative should be found for its inflammation-limiting benefits. Photo by Amit Lahav on Unsplash

Guar gum is derived from guar beans, and is a common food additive and dietary fibre. Surprisingly, limited inflammation and delayed the onset of multiple sclerosis (MS) symptoms in mice, according to new research published in Cell Reports.

“The rapid increase of autoimmune and inflammatory disorders in industrialised countries in the last few decades indicates dietary choices are one environmental factor contributing to incidence,” said Dr Lisa Osborne, senior study researcher on the study.

“Dietary fibres are potent modulators of immune responses and can control inflammation in multiple diseases, but they’re a very biochemically diverse family. Our study gives us a clearer window into the potential of several sources of fibre in maintaining immune health.”

Dr Osborne and colleagues exposed groups of mice to a variety of diets: a control diet with 5% cellulose fibre, a no-fibre diet, or diets enriched (30%) with fibre in either resistant starch, inulin, pectin, or guar gum. Guar gum was the only fibre type that significantly limited the MS-like symptoms. 

Guar gum (guaran) is extracted from guar beans, and is often used as an additive to thicken and stabilise food and animal feed, and in industrial applications.

“Guar beans aren’t that common in western diets, and the gum isn’t used at these high levels as an additive in the west,” says Naomi Fettig, first author on the study and a PhD student with the Department of Microbiology and Immunology at UBC.

“Experts have consistently been saying fibre is good for you – and a variety of fibre sources is important to immune health – but there hasn’t been very much critical work into identifying how the body responds to different fibre types. It’s fascinating that this particular source has such an impact.”

In the US and Canada, the average daily intake of fibre is 15g – current recommendations are 30g, with no regard to specific fibre type. “Incorporating guar beans might be challenging to achieve at the doses we gave to mice,” says Dr Osborne. “But a guar gum derivative, partially hydrolysed guar gum, is commercially available as a prebiotic.”

After the gum is broken down by the gut microbiota of mice, the resulting molecules appeared to reduce the activity and proliferation of a type of CD4+ T cells, Th1 cells, which have a key role in triggering the autoimmune response, which can lead to MS-like symptoms in mice. The effects of fibre on Th1 cells remained largely unknown prior to this study, and these findings suggest that the biochemical differences in fibre structures can influence diverse immune pathways.  

Dr Osborne and her lab now want to explore the potential benefits in humans – including developing a more detailed understanding of the molecular picture, which might help design therapeutics that offer the benefits of such high guar gum diets in a more practical form.

Source: University of British Columbia

Categories : Diseases, Syndromes and Conditions Environmental EffectsTags :

Wealth Divide, not Vitamin D, Explains Differing MS Rates

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Differences in vitamin D exposure have been thought to explain why people who live farther from the equator are more likely to develop multiple sclerosis (MS). But countries farther from the equator are also more likely to be wealthier. A new analysis published in Neurology shows that the amount a country spends on health care may help explain this relationship between MS and latitude.

According to study author Deanna Saylor, MD, MHS, the results suggest that MS rates may be greatly underestimated in low-income countries with lower health care spending, which means that people have less access to neurologists who have the expertise to diagnose MS and MRI scanners that are needed to make the diagnosis.

Researchers analysed data from scientific studies and databases to determine current rates of MS in 203 countries and territories. Countries were then grouped into world regions and by income levels.

Rates of MS varied by region and income level. For example, in high-income countries an average of 46 of every 100 000 people had MS, compared to 10 people per 100 000 in low-income countries. Health care spending per capita was $2805 for high-income countries, compared to $45 in low-income countries.

For each location, researchers examined gross domestic product per capita, current health expenditure per capita, income levels, the availability of brain scans to diagnose MS, the number of neurologists per capita and universal health care. They also reviewed lifestyle factors such as obesity and tobacco use.

Once the researchers adjusted the data for other factors that could affect the risk of MS, such as age and sex, they found that health care spending and latitude were strongly associated with MS rates. The research showed that, with every increase of one standard deviation in health expenditure per capita, a country’s MS prevalence increased by 0.49. Alternatively, with every increase of one standard deviation in latitude, a country’s MS prevalence increased by 0.65.

Researchers also found that health care spending explained some, but not all, of the link between latitude and MS. After adjusting for other factors, the link between latitude and MS decreased by more than 20% when health care expenditure per capita was considered.

The availability of universal health care was associated with rates of MS in all world regions, except Southeast Asia, with universal health care tied to higher rates of MS.

In high-income countries, rates of MS were linked to most factors, including gross domestic product per capita, current health expenditure per capita, and the number of neurologists, but not tobacco use and obesity or the number of MRI units per capita. However, in low-income countries, there were no associations with any of these factors, which may be explained by a lack of significant variation in data from these countries, Saylor said.

According to Dr Saylor, the finding that current health expenditure per capita was very strongly linked with national rates of MS further supports the hypothesis that greater investment in health care leads to more robust reporting of rates of MS. She also said the minimal links between rates of MS and lifestyle factors such as tobacco use and obesity run counter to prior assumptions that lifestyle and consumption behaviours explain the large portions of regional differences in reported rates of MS.

Dr Saylor said strategies are urgently needed for the accurate assessment of the burden of MS in low-income countries, and these lower reported MS can obscure the need for training and funding regarding MS.

A limitation of the study is that different data sources may have collected information during different time periods or used different methods, which could affect the accuracy of estimates.

Source: American Academy of Neurology

Categories : Diseases, Syndromes and ConditionsTags :

Reduced Risk of Relapse in MS Sufferers Taking Cladribine

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A healthy neuron.
A healthy neuron. Credit: NIH

A study using real-world data has shown that multiple sclerosis (MS) sufferers taking cladribine were less likely to experience disease relapse than those who took other oral disease-modifying therapies.

Relapse and discontinuation outcomes favoured cladribine tablets over oral fingolimod, dimethyl fumarate, and teriflunomide. The findings were reported Helmut Butzkueven, PhD, of Monash University at ACTRIMS Forum 2022, the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.

For the study, researchers drew on data from the MSBase registry of more than 79 000 people with MS worldwide. Few clinical trials or real-world studies are available that compare the effectiveness of cladribine tablets to other oral disease-modifying therapies, the researchers noted.

“Many treatment choices that patients and their care teams have to make are not or not yet examined in classical randomised trials,” Dr Butzkueven told MedPage Today. “Sophisticated analysis of data gathered systematically and prospectively in clinical care is proving a valuable alternative to examine and compare the outcomes of different treatment choices in all kinds of scenarios.”

“Oral agents for use in relapsing MS are very convenient and effective treatment choices,” he added. “This work directly compares outcomes for people with MS who chose cladribine tablets versus other oral drugs.”

The chemotherapy drug cladribine, was recently approved by the FDA for active secondary progressive disease and relapsing MS. This was based on results from trial data showing that cladribine significantly decreased the number of MS relapses and reduced the progression of disability compared with placebo.

GLIMPSE was a longitudinal study that included data for 3475 MS patients on either cladribine, fingolimod, dimethyl fumarate or teriflunomide.

The 633 patients taking cladribine were propensity-score matched with those taking oral comparators on various factors such as age, sex and country.

In pairwise comparisons, cladribine versus fingolimod had 520 matched participants per group: the annualised relapse rate (ARR) was 0.09 compared with 0.15, respectively, the hazard ratio (HR) for time to first relapse was 0.60, and the HR for time to discontinuation was 0.22.

For cladribine versus dimethyl fumarate (450 people per group), the ARR was 0.10 compared with 0.15 the HR for time to first relapse was 0.58, and the HR for time to discontinuation was 0.10.

The cladribine versus teriflunomide (458 people per group) comparisons showed that the ARR was 0.09 compared with 0.17, the HR for time to first relapse was 0.33, and the HR for time to discontinuation was 0.10.

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags :

Link Between Consuming Dairy Products and MS Flareups Explained

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The reason why multiple sclerosis (MS) sufferers often complain of more severe disease symptoms after consuming dairy products may be down to the milk protein casein, which can trigger inflammation targeting the myelin sheath, according to a study published in the journal PNAS.

This link was demonstrated in mice, but there was evidence of a similar mechanism in humans. The researchers therefore recommend that certain groups of MS sufferers avoid dairy products.

“We hear again and again from sufferers that they feel worse when they consume milk, cottage cheese or yoghurt,” explained Professor Stefanie Kürten from the Institute of Anatomy at University Hospital Bonn. “We are interested in the cause of this correlation.”

The professor of neuroanatomy is considered a renowned expert on multiple sclerosis. “We injected mice with different proteins from cow’s milk,” she said. “We wanted to find out if there was a constituent that they were responding to with symptoms of disease.”

When they administered the cow’s milk constituent casein together with an effect enhancer to the animals, the mice went on to develop neurological disorders. Electron microscopy showed damage to the insulating myelin sheath, which normally prevents short circuits and significantly accelerates stimulus conduction.

In multiple sclerosis, the body’s immune system destroys the myelin sheath. Consequences range from paresthaesia and vision problems to movement disorders. With patients ending up in a wheelchair. In mice, the myelin sheath was also massively perforated, apparently triggered by casein administration. “We suspected that the reason was a misdirected immune response, similar to that seen in MS patients,” explained Rittika Chunder, a postdoctoral fellow in Prof. Kürten’s research group. “The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin.”

Such cross-reactivity can occur when two molecules share some similar parts, causing the immune system to mistake them for each other. “We compared casein to different molecules that are important for myelin production,” Dr Chunder said. “In the process, we came across a protein called MAG. It looks markedly similar to casein in some respects – so much so that antibodies to casein were also active against MAG in the lab animals.”

This means that in the casein-treated mice, the body’s own defences were also directed against MAG, destabilising the myelin. But to what extent can the results be transferred to people with MS? To answer this question, the researchers added casein antibodies from mice to human brain tissue. These did indeed accumulate in the cells responsible for myelin production in the brain.

The study found that the antibody-producing B cells in the blood of people with MS respond particularly strongly to casein. It is possible that at some point while consuming milk, the affected individuals developed an allergy to casein. Now, on consuming dairy products, the immune system produces masses of casein antibodies, which due to cross-reactivity with MAG, also damage the myelin sheath.

However, this only affects MS patients who are allergic to cow’s milk casein. “We are currently developing a self-test with which affected individuals can check whether they carry corresponding antibodies,” said Prof Kürten. “At least this subgroup should refrain from consuming milk, yogurt, or cottage cheese.”

It is possible that cow’s milk also increases the risk of developing MS in healthy individuals. Because casein can also trigger allergies in them – which is probably not even that rare. Once such an immune response exists, cross-reactivity with myelin can in theory occur. However, this does not mean that hypersensitivity to casein necessarily leads to the development of multiple sclerosis, Prof Kürten stressed. This would presumably require other risk factors. This connection is concerning worrying, said Prof Kürten, as “Studies indicate that MS rates are elevated in populations where a lot of cow’s milk is consumed.”

Source: University of Bonn

Categories : Diseases, Syndromes and ConditionsTags :

In MS, Twin Study Reveals Disease-causing T Cells

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By studying the immune system of pairs of monozygotic twins to rule out genetics in cases of multiple sclerosis, researchers may have discovered a smoking gun: precursor cells of the disease-causing T cells.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system CNS and the most common cause of neurological impairment in young adults. In MS, the patient’s own immune system attacks the CNS, resulting in cumulative neurological damage. The cause of MS still unclear but a variety of genetic risk factors and environmental influences have already been linked to the disease.

Genetics have already been found to be a necessary condition for developing multiple sclerosis. “Based on our study, we were able to show that about half of the composition of our immune system is determined by genetics,” said Florian Ingelfinger, a PhD candidate at the UZH Institute of Experimental Immunology. The study shows that these genetic influences, while always present in MS patients, are not on their own sufficient to trigger multiple sclerosis. In the study, 61 pairs of monozygotic twins where one twin is affected by MS whereas the co-twin is healthy were examined. From a genetic point of view, the twins were thus identical. “Although the healthy twins also had the maximum genetic risk for MS, they showed no clinical signs of the disease,” said Lisa Ann Gerdes.

With this cohort of twins, the researchers were  tease out environmental differences. “We are exploring the central question of how the immune system of two genetically identical individuals leads to significant inflammation and massive nerve damage in one case, and no damage at all in the other,” explained Professor Burkhard Becher, leader of the research team. Using identical twins let the researchers block out the genetic influence and focus on the immune system changes that were ultimately responsible for triggering MS in one twin.

The researchers harnessed state-of-the-art technologies to describe the immune profiles of the twin pairs in great detail. “We use a combination of mass cytometry and the latest methods in genetics paired with machine learning to not only identify characteristic proteins in the immune cells of the sick twin in each case, but also to decode the totality of all the genes that are switched on in these cells,” Florian Ingelfinger explained. 

“Surprisingly, we found the biggest differences in the immune profiles of MS affected twins to be in the cytokine receptors, ie the way immune cells communicate with one another. The cytokine network is like the language of the immune system,” said Ingelfinger. Increased sensitivity to certain cytokines leads to greater T cell activation in the bloodsteams of patients with multiple sclerosis. These T cells are more likely to migrate into the CNS and cause damage there. The identified cells were found to have the characteristics of recently activated cells, which were in the process of developing into fully functional T cells. “We may have discovered the cellular big bang of MS here – precursor cells that give rise to disease-causing T cells,” said Prof Becher.

“The findings of this study are particularly valuable in comparison to previous studies of MS which do not control for genetic predisposition,” said Prof Becher. “We are thus able to find out which part of the immune dysfunction in MS is influenced by genetic components and which by environmental factors. This is of fundamental importance in understanding the development of the disease.”

The study findings were reported in Nature.

Source: University of Zurich

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Meat, Gut Bacteria and Multiple Sclerosis

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Gut microbiome. Credit: Darryl Leja, NIH

There appears to be a link between eating meat, gut bacteria and multiple sclerosis, according to new research published in EBioMedicine. The study teased out subtle connections that could lead to a better understanding of the causes of the disease.

The autoimmune disease multiple sclerosis (MS) is more prevalent in specific regions, particularly the northern mid-latitudes, suggesting that geography is somehow linked to the disease, perhaps involving diet. However, the exact relationships between diet, immune response, and MS has been a mystery. What exactly triggers the body to attack the myelin sheaths in MS in the first place is unknown.

Growing evidence suggests that bacteria might play a role. Gut bacteria affect the immune system, and diet affects the gut. Researchers studied the gut microbiome, immune systems, diet, and blood metabolites in 25 MS patients and 24 healthy controls to look for any subtle but important correlations.

“We found a number of gut bacteria associated with MS and severity of disability of MS patients,” said Dr Yanjiao Zhou. “We also found increased autoimmune markers and signature metabolites in MS. But what is really interesting is how these systems connect with each other, and how diet is involved in these connections. Using multi-OMICS approaches, we try to close the loop and show the associations between multiple systems.”

Meat eating was the strongest link in their analysis, where higher meat consumption saw a decrease in the population of Bacteroides thetaiotaomicron, a bacteria associated with digesting carbohydrates from vegetables.

Higher meat consumption, seen in the MS patients, was also linked to an increase in T-helper 17 cells in the immune system, and an increase in S-adenosyl-L-methionine (SAM) in their blood.

Meat eating was not a predictor of MS. But the evidence suggested that, in MS, something causes gut bacteria to disassociate with the immune system, leading to heightened T-helper 17 cells and autoimmune attacks on the nervous system. And it tends to be associated with eating meat.

Future research aims to recruit more volunteers, including those with more severe MS. Eventually they hope to understand more of the cause-and-effect between diet, bacterial ecosystems in the gut, and immune response, and potentially help prevent or mitigate MS symptoms in people suffering from the disease.

Source: University of Connecticut