Posted on Multiple Sclerosis

Dozens of gut bacteria associated with multiple sclerosis


An international research consortium led by UC San Francisco scientists has shown significant differences between the gut bacteria profiles of multiple sclerosis (MS) patients and healthy individuals, as well as between MS patients receiving different drug treatments. While some of these changes had been reported before, most are reported for the first time. The group also uncovered novel mechanisms by which these bacteria may potentially influence disease development and treatment response. 

In recent years, scientists have increasingly made connections between intestinal bacteria and a number of diseases—not just diseases of the gut—including diabetes and arthritis. The field of microbiome studies really opened up with advances in DNA sequencing in the early 2010s that allowed scientists to get a detailed picture of what bacteria are present in samples of stool, blood, mucosal tissue, and skin.

Until recently, most of the experimental evidence suggesting a link between gut bacteria and MS had come from research in mice. Studies in humans had offered inconsistent results—in part because of smaller numbers of participants, and a failure to screen out the effects of the environment on an individual’s microbiome. Where one lives—rural or urban, on a mountain top or next to an oil refinery—plays a big role in the bacteria our bodies harbor. 

To get around these limitations, the consortium of scientists participating in the International Multiple Sclerosis Microbiome Study (IMSMS) recruited a large number of MS patients from three continents and selected genetically unrelated controls from the same households as the patients. It was the first time this methodology had been used in such a large study. The study, which was published in Cell on September 15, 2022, describes differences between the gut microbiome profiles of 576 patients and an equal number of household controls in the United States, the United Kingdom, Spain and Argentina. The findings could lead to new therapeutics that involve either manipulating the microbiome or dietary interventions.

“This is the reference study that will be used by the field for years to come,” said Sergio Baranzini, PhD, the Heidrich Family and Friends Endowed Chair in Neurology and member of the UCSF Weill Institute for Neurosciences, who is the lead author on the new study. 

With their innovative protocol, Baranzini and his colleagues were able to identify dozens of new bacteria species associated with MS and confirm other species that had previously only been associated with the disease. “We were surprised by the number of species that were differentially present in MS when compared to controls,” said Baranzini. They also found that the largest source of variation in bacteria species was linked to the geographical location of the participants, which confirmed the importance of location and local variations in diet to the gut microbiome. The second largest source of variation was a participant’s disease status, which is what the researchers had expected. 

The study was the second in a series being conducted by iMSMS, an international consortium established in 2015 for the purpose of determining the role of gut bacteria in MS disease susceptibility, progression, and response to therapy. The first study validated the household control protocol, showing that it increases statistical power in population-based microbiome studies. 

The findings of the study are primarily descriptive, acknowledges Baranzini. “When looking at the microbiome, there are two questions that usually are asked,” he said. “The first one is ‘Who’s there?’ This is what we’re trying to answer in this paper. The second is, ‘What are they doing?’” 

Answering the second question requires mechanistic studies with individual bacteria to understand their metabolic profiles. Still, the researchers got some hints at what the bacteria they found are doing by studying the potential pathways that these bacteria encode. 

“Knowing which genes from which species we are able to identify in cases and controls, we can now start to reconstruct which potential pathways are active in patients and controls,” said Baranzini. 

For example, some of the bacteria the team found to be associated with MS seem to play a role in helping humans process fiber from plants, the byproducts of which tend to be found in increased concentrations in MS patients. Other species seem to have an influence on inflammation and the energy production machinery of the cell.  

The researchers also found that patients treated with an immunomodulator known as interferon beta-1a, the oldest therapy for MS, have lower concentrations of short-chain fatty acids in their feces and higher concentrations in their blood. Short-chain fatty acids are known for their anti-inflammatory properties, so this suggests that interferon works by increasing the transportation of these molecules from the gut to the blood stream, which Baranzini said could be one of the mechanisms of action of interferon. 

The iMSMS group will continue to recruit patients, expanding to Germany and Canada, until the total number of participants in the cohort reaches 2000. Starting this fall, they will also follow a subset of patients over two years to see how their gut microbiota change in response to treatment, lifestyle changes and disease progression. All of the data from these studies will be publicly available. 

“This is an example of how big science can only be achieved collaboratively,” he added. “In the iMSMS, we really brought together the best and the brightest researchers in the microbiome research field and in multiple sclerosis, and they’re all pulling towards the same objective.” 

Posted on Autism

Anti-diarrhoea medication could be used as a therapy for autism! Does this article not sound weird to you?

Can you teach an old drug new tricks? Although drug treatments for the core egs of autism are not currently available, could an existing drug provide a new treatment, even if it previously had no association with autism ? This was the question asked by a new study in the journal Frontiers in Pharmacology. The researchers used a computer model that encompasses proteins involved in autism and the way they interact.

By looking at how different drugs affected proteins in the system, they identified potential candidates to treat it. A commonly used antidiarrheal drug called loperamide was the most promising candidate, and the researchers have an interesting hypothesis about how it may work to treat autism symptoms. Some of the most common symptoms in autism involve difficulties with social interaction and communication.

“There are no medications currently approved for the treatment of social communication deficits, the main symptom in A*D,” said Dr Elise Koch of the University of Oslo, lead author on the study. “However, most adults and about half of children and adolescents with Aautism are treated with antipsychotic drugs, which have serious side effects or lack efficacy in autism .”

Repurposing drugs as new treatments

In an effort to find a new way to treat , the researchers turned to drug repurposing, which involves exploring existing drugs as potential treatments for a different condition. The approach has plenty of benefits, as there is often extensive knowledge about existing drugs in terms of their safety, side-effects and the biological molecules that they interact with in the body.

To identify new treatments for , the researchers used a computer-based protein interaction network. Such networks encompass proteins and the complex interactions between them. It is important to account for this complexity when studying biological systems, as affecting one protein can often have knock-on effects elsewhere.

The researchers constructed a protein interaction network that included proteins associated with . By investigating existing drugs and their interaction with proteins in the network, the team identified several candidates that counteract biological process underlying .

The most promising drug is called loperamide, which is commonly used for diarrhea. While it might seem strange that an anti-diarrheal drug could treat core symptoms, the researchers have developed a hypothesis about how it may work.

From an upset gastrointestinal system to

Loperamide binds to and activates a protein called the μ-opioid receptor, which is normally affected by opioid drugs, such as morphine. Along with the effects that you would normally expect from an opioid drug, such as pain relief, the μ-opioid receptor also affects social behavior.

In previous studies, genetically engineered mice that lack the μ-opioid receptor demonstrated social deficits similar to those seen in . Interestingly, drugs that activate the μ-opioid receptor helped to restore social behaviors.

These results in mice highlight the tantalizing possibility that loperamide, or other drugs that target the μ-opioid receptor, may represent a new way to treat the social symptoms present in , but further work is required to test this hypothesis. In any case, the current study demonstrates the power of assuming that old drugs may indeed learn new tricks.       

Posted on Diabetes

Seven healthy lifestyle habits may reduce dementia risk for people with diabetes

A combination of seven healthy lifestyle habits including sleeping seven to nine hours daily, exercising regularly and having frequent social contact was associated with a lower risk of dementia in people with type 2 diabetes, according to a study published in the September 14, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Type 2 diabetes is a worldwide epidemic that affects one in 10 adults, and having diabetes is known to increase a person’s risk of developing dementia,” said study author Yingli Lu, MD, PhD, of Shanghai Jiao Tong University School of Medicine in China. “We investigated whether a broad combination of healthy lifestyle habits could offset that dementia risk and found that people with diabetes who incorporated seven healthy lifestyle habits into their lives had a lower risk of dementia than people with diabetes who did not lead healthy lives.”

For the study, researchers looked at a health care database in the United Kingdom and identified 167,946 people 60 or older with and without diabetes who did not have dementia at the start of the study. Participants completed health questionnaires, provided physical measurements and gave blood samples.

For each participant, researchers calculated a healthy lifestyle score of zero to seven, with one point for each of seven healthy habits. Habits included no current smoking, moderate alcohol consumption of up to one drink a day for women and up to two a day for men, regular weekly physical activity of at least 2.5 hours of moderate exercise or 75 minutes of vigorous exercise, and seven to nine hours of sleep daily. Another factor was a healthy diet including more fruits, vegetables, whole grains and fish and fewer refined grains, processed and unprocessed meats. The final habits were being less sedentary, which was defined as watching television less than four hours a day, and frequent social contact, which was defined as living with others, gathering with friends or family at least once a month and participating in social activities at least once a week or more often.

Researchers followed participants for an average of 12 years. During that time, 4,351 people developed dementia. A total of 4% of the people followed only zero to two of the healthy habits, 11% followed three, 22% followed four, 30% followed five, 24% followed six and 9% followed all seven.

People with diabetes who followed two or fewer of the seven healthy habits were four times more likely to develop dementia than people without diabetes who followed all seven healthy habits. People with diabetes who followed all of the habits were 74% more likely to develop dementia than those without diabetes who followed all the habits.

For people with diabetes who followed all the habits, there were 21 cases of dementia for 7,474 person years or 0.28%. Person-years represent both the number of people in the study and the amount of time each person spends in the study. For people with diabetes who followed only two or fewer habits, there were 72 cases of dementia for 10,380 person years or 0.69%. After adjusting for factors like age, education and ethnicity, people who followed all the habits had a 54% lower risk of dementia than those who followed two or fewer. Each additional healthy habit people followed was associated with an 11% decreased risk of dementia. The association between healthy lifestyle score and dementia risk was not affected by medications people took or how well they controlled their blood sugar.

“Our research shows that for people with type 2 diabetes, the risk of dementia may be greatly reduced by living a healthier lifestyle,” Lu said. “Doctors and other medical professionals who treat people with diabetes should consider recommending lifestyle changes to their patients. Such changes may not only improve overall health, but also contribute to prevention or delayed onset of dementia in people with diabetes.”

A limitation of the study was that people reported on their lifestyle habits and may not have remembered all details accurately. Lifestyle changes over time were also not captured.

Posted on Diabetes

Six-country European survey finds over half of adults with diabetes in the UK and Italy experience anxiety

Six-country European survey finds over half of adults with diabetes in the UK and Italy experience anxiety
Six-country European survey finds over half of adults with diabetes in the UK and Italy experience anxiety


A survey of adults with type 1 and type 2 diabetes from six Western European countries highlights the unique burden of mental health issues on people with diabetes and suggests a link between blood sugar management and severity of anxiety.

“Our survey results underline how vulnerable adults with diabetes are to generalised anxiety. In particular, women with diabetes and those younger than 45 may be more susceptible to experiencing anxiety, emphasising the need for greater support”, says Ms Cox.

She adds, “Our findings also indicate a link between blood sugar management and severity of anxiety. This underscores the need for a more integrated approach to diabetes management and mental health support to both minimise anxiety and improve blood sugar metrics targeted at high-risk groups.”

Previous research shows that people with diabetes have higher rates of mental health disorders, including generalised anxiety disorder (characterised by persistent and excessive worry), compared to the general population. But there has been little research on the relationship between diabetes management and generalised anxiety.

For this study, researchers conducted an online survey to collect data on demographic characteristics, anxiety, and blood sugar management metrics in 3,077 adults from the dQ&A EU research panel (average age 44, 52% female) living with type 1 diabetes (66%) or type 2 diabetes (34%) in France, Germany, Italy, Netherlands, Sweden, and the UK. Data were collected between October and November 2021. All respondents were compensated for completing the survey (€12 EUR).

Respondents were asked for their most recent haemoglobin A1c level (HbA1c, a measure of blood sugar control) if they knew it (2,561 participants); and those who used glucose sensors (2,011) were asked about the percentage of time in a typical day they spent in the target blood sugar range (between 70 and 180 mg/dl). All respondents completed the Generalized Anxiety Disorder questionnaire (GAD-7) to screen for, and measure, severity of anxiety.

The analyses found that people with diabetes living in Italy and the UK reported the highest rates of anxiety (63% and 51%, respectively), while those in the Netherlands reported the lowest rates (39%).

Across all six European countries studied, women with diabetes were more likely to report experiencing anxiety than men (57% vs 39%). And anxiety was more common among those younger than 45 years than those older—59% and 34%, respectively.

The analyses also found that individuals with higher HbA1c over the past few months (greater than 7%) were more likely than those with lower HbA1c (equal or less than 7%) to report moderate (13% vs 10%) or severe anxiety (6% vs 4%).

Additionally, respondents using glucose sensors who spent less than 70% of a typical day in the target blood sugar range reported almost twice the rate of moderate or severe anxiety compared to those who spent 70% or more of their time in the target range (22% vs 14%).

“It is crucial that people with diabetes who experience challenges with their mental health reach out to their healthcare providers or mental healthcare practitioners for support”, says Cox. “Effective treatments are available and can considerably improve quality of life.”

Posted on autoimmune conditions, Cardiovascular disease

Study finds higher complication rate after a heart attack in people with autoimmune disease

Rheumatoid arthritis linked to irregular heart rhythm


After a heart attack, people with an autoimmune disease were more likely to die, develop heart failure or have a second heart attack compared to people without an autoimmune disease, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

Autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosis and psoriasis, are known to increase risk of cardiovascular disease, likely due to multiple factors. People with an autoimmune disease have a higher prevalence of traditional cardiovascular risk factors (such as high blood pressure, Type 2 diabetes or kidney disease), in addition to aspects of autoimmune disease that are also linked to higher cardiovascular risk, such as chronic inflammation, autoimmune antibodies and long-term use of steroid medications. A new study examined whether having an autoimmune disease, compared to not having one, affects a person’s health status after a heart attack.

“The evidence about the risk of adverse events after heart attack for people with autoimmune disorders is less robust than evidence for people without these disorders, and mainly from small or single-center studies,” said Amgad Mentias, M.D., M.Sc., senior author of the study and an assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine in Cleveland. “We conducted our study to examine, in a large cohort, whether there is any difference in the treatment of heart attack patients with versus without autoimmune diseases, and whether there is a difference in risk of death, heart failure or recurrent heart attacks over the long-term.”

The researchers identified 1,654,862 people in the U.S. ages 65 and older in the Medicare Provider Analysis and Review (MedPAR) File who were admitted to the hospital with a heart attack diagnosis between 2014 and 2019. MedPAR is a government database of every hospital inpatient bill in the U.S. submitted to Medicare for payment. Of those records, 3.6% (60,072) had an inflammation-causing autoimmune disease noted in their charts within the previous year. The most common condition was rheumatoid arthritis, followed by systemic lupus, psoriasis, systemic sclerosis and myositis/dermatomyositis. They found several important differences among people with vs. without autoimmune disease who had heart attacks:

  • People with an auto immune disease were slightly younger – average age was 77.1 years vs. 77.6 years for those without an autoimmune disease.
  • More of those with an autoimmune disease were women (66.9% vs. 44.2%).
  • Those with autoimmune disease were more likely to have had a non-ST-elevation myocardial infarction (NSTEMI) heart attack (updated from 77.1 to 77.3) (77.3% vs. 74.9%), and they were less likely to have an ST-elevation myocardial infarction (STEMI) heart attack (18.7% vs. 22.1%).

An NSTEMI, the most common type of heart attack recorded in the database, is caused by partial blockage of one of the coronary arteries that feeds oxygen-rich blood to the heart muscle. A STEMI heart attack, usually more dangerous, is from a complete blockage of one or more of the heart’s main arteries.

The researchers matched each heart attack patient record with autoimmune disease to records of three heart attack patients without autoimmune disease based on age, sex, race and type of heart attack. After matching (and excluding people who had not been enrolled in Medicare for at least one year prior to their heart attack), the investigators compared health outcomes for about 2 years. The final dataset included 59,820 heart attack records of people with an autoimmune disorder and 178,547 of those without an autoimmune disorder.

The analysis found that people with an autoimmune disease were:

  • 15% more likely to die from any cause;
  • 12% more likely to be hospitalized for heart failure;
  • 8% more likely to have another heart attack; and
  • 6% more likely to have an additional artery-opening procedure (if they had received one at the time of their heart attack).

“Patients with autoimmune disease and cardiovascular disorders are preferably managed by a cardio rheumatologist in conjunction with a rheumatologist to optimize cardiovascular health. Traditional CVD risk factors are accentuated in this population and how these risk factors manifest is also unique,” said lead study author Heba Wassif, M.D., M.P.H., an assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine and director of cardio-rheumatology at the Cleveland Clinic.

“For example, cholesterol levels are affected by inflammation, therefore patients with active inflammatory disease have lower levels of cholesterol, a phenomenon known as the lipid paradox,” Wassif said. “Physical activity, which is highly recommended to improve cardiovascular outcomes, may be limited by joint pain. Furthermore, some disease modifying agents may increase cardiovascular risk. Knowledge of these nuances and a team-based approach may improve outcomes.”

The researchers also found that people with an autoimmune disease were less likely to have heart catheterization to assess narrowed coronary arteries or to undergo an artery-opening procedure or bypass surgery regardless of the type of heart attack.

“It is possible that the people with an autoimmune disease were not healthy enough to undergo those procedures, or their coronary anatomy was less amenable to interventions to reopen narrowed or clogged vessels,” Mentias said. These issues may place them at higher risk of procedure-related complications. “When feasible, however, if someone is a suitable candidate, these procedures should be considered as options. The presence of autoimmune disease by itself should not preclude someone from potentially life-saving procedures.”

The researchers did not have information on the anatomy of patients’ coronary arteries, which limited the ability to assess whether anatomical differences may have influenced decision-making about vessel-opening procedures. The analysis is also limited by not having laboratory data on the severity and activity of patients’ autoimmune disease, making it impossible for the researchers to assess whether the risk of complications and death following heart attack is higher in patients with severe forms of autoimmune disease compared with those who have a milder form or disease in remission.

“Future research is needed on medications and interventions that might reduce the heightened risk for poor outcomes in heart attack patients with autoimmune disease,” Wassif said, “such as investigating whether different immune modulators and immune-suppressant therapies used to control and treat the autoimmune disease have any impact in improving post-heart-attack outcomes.”