Researchers design a probiotic to suppress autoimmunity in the brain

Brigham researchers are working on a new approach to target autoimmunity in the brain leverages designer bacteria to make treatment safer and more effective.

Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, have designed a probiotic to suppress autoimmunity in the brain, which occurs when the immune system attacks the cells of the central nervous system. Autoimmunity in the brain is at the core of several diseases, including multiple sclerosis. In a new study, researchers demonstrated the treatment's potential using preclinical models of these diseases, finding that the technique offered a more precise way target brain inflammation with reduced negative side effects compared to standard therapies. The results are published in Nature.

Engineered probiotics could revolutionize the way they treat chronic diseases. When a drug is taken, its concentration in the bloodstream peaks after the initial dose, but then its levels go down. However, if they can use living microbes to produce medicine from within the body, they can keep producing the active compound as its needed, which is essential when they consider lifelong diseases that require constant treatment."

Francisco Quintana, PhD, Lead Author, Ann Romney Center for Neurologic Diseases at Brigham and Women's Hospital

Autoimmune diseases affect approximately 5-8% of the U.S. population. Despite their widespread prevalence, there are limited treatment options for most of these diseases. Autoimmune diseases that affect the brain, such as MS, are particularly challenging to treat due to their location – many pharmacological therapies can't effectively access the brain due to the blood-brain barrier, a protective mechanism that separates the brain from the circulatory system.

To look for new ways to treat autoimmune diseases, the researchers studied dendritic cells, a type of immune cell that is abundant in the gastrointestinal tract and in the spaces around the brain. These cells help control the rest of the immune system, but scientists don't yet know their role in autoimmune diseases. By analyzing dendritic cells in the central nervous system of mice, they were able to identify a biochemical pathway that dendritic cells use to stop other immune cells from attacking the body.

"The mechanism they found is like a brake for the immune system," said Quintana. "In most of us, it's activated, but in people with autoimmune diseases, there are problems with this brake system, which means the body has no way to protect itself from its own immune system."

The researchers found that this biochemical brake can be activated with lactate, a molecule involved in many metabolic processes. The researchers were then able to genetically engineer probiotic bacteria to produce lactate.

"Probiotics are nothing new – we've all seen them sold as supplements and marketed as a way to promote health," said Quintana. "By using synthetic biology to get probiotic bacteria to produce specific compounds relevant to diseases, they can take the benefits probiotics and amp them up to the max."

They tested their probiotic in mice with a disease closely resembling MS, and they found that even though the bacteria live in the gut, they were able to reduce the effects of the disease in the brain. They did not find the bacteria in the bloodstream of the mice, suggesting that the effect they observed was a result of biochemical signaling between cells in the gut and in the brain.

"We've learned in accurate decades that the microbes of the gut have a significant impact on the central nervous system," said Quintana. "One of the reasons they focused on multiple sclerosis in this study was to determine whether they can leverage this effect in treating autoimmune diseases of the brain. The results suggest they can."

While the current study only examined the effect of the probiotic in mice, the researchers are optimistic that the approach could be readily translated into the clinic because the strain of bacteria they used to create their probiotic has already been tested in humans. The researchers are also working to modify their approach for autoimmune diseases that affect other parts of the body, particularly gut diseases like inflammatory bowel syndrome.

Quintana and colleagues are working to launch a company in collaboration with Mass General Brigham Ventures. As a world-recognized leader in research and innovation, discoveries at Mass General Brigham have led to the creation of hundreds of new companies that have spurred scientific innovation and economic growth across Massachusetts, nation, and globe. These companies enable patients around the world to benefit from Mass General Brigham discoveries.

"The ability to use living cells as a source of medicine in the body has tremendous potential to make more personalized and precise therapies," said Quintana. "If these microbes living in the gut are powerful enough to influence inflammation in the brain, we're confident we'll be able to harness their power elsewhere as well."

Source:

Journal reference:

Sanmarco, L. M., et al. (2023). Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells. Nature. doi.org/10.1038/s41586-023-06409-6.

Mother-of-three Portia Clarke dumps boyfriend so she could get extra benefitss

By Rosie Taylor for the Daily Mail

Published: 11:01 EDT, 21 May 2014 | Updated: 12:22 EDT, 22 May 2014

A mother dumped the father of one of her three children so she could claim more benefits.

Portia Clarke, 34, told him to move out of their home so she could rake in nearly £17,000 a year in handouts as an unemployed single mother.

She grew frustrated that the £13,000 salary former partner Paul Burke earned as a factory worker reduced her entitlement to welfare – and left her little money for splashing out on luxury items.

'Sponging': Aspiring glamour model Portia Clarke now spends handouts on luxury goods such as foreign holidays

The aspiring glamour model, who has never worked, now has her rent and council tax paid for by the state – and spends much of the £1,000 monthly disposable income she gets on nights out, clothes and five-star holidays to Turkey.

Mr Burke, 24, decided that living apart was not working and the couple split after four years together. Now their two-year-old daughter and Miss Clarke’s two children from previous relationships, aged 12 and seven, are living without the father figure they all call ‘Dad’.

Speaking from her three-bedroom terraced council house in Middleton, Greater Manchester, she told the Mail: ‘The children miss having him around but they’re happy because they get to see him on weekends.’

In an interview with Closer magazine, out this week, she said she had no regrets about moving Mr Burke out of their home.

Money: Portia Clarke (left) admitted asking her boyfriend Paul Burke (right) to move out

‘Paul only earned £800 a month at the factory, and by the time we’d paid rent they didn’t have much left. I couldn’t buy myself nice clothes or go on holidays,’ she said.

Miss Clarke, whose home contains expensive goods including a 50-inch TV and a leather-style sofa, now receives a range of handouts including jobseeker’s allowance, income support, child benefits and tax credits.

She claims it is a better alternative to ‘flogging my guts out for low pay’ when she left beauty college at 18.

After falling pregnant with her first child she was given a council house and £600 a month in benefits, which increased by £200 for her second child. After meeting Mr Burke she was reluctant for him to move in as it meant paying council tax and rent and losing some housing benefit and income support. She eventually agreed when she became pregnant with his child.

The couple got engaged but rowed about money, with Miss Clarke saying she ‘resented’ that her benefits had been cut because of Mr Burke’s modest income – even though it was enough to cover their £400 monthly outgoings.

‘Paul wanted me to get a job, but I knew I’d never find anything that paid decent money,’ she added. ‘I asked Paul to get a better paid job, but he couldn’t find anything, so I suggested he could move out and they could carry on the relationship, but he wasn’t having any of it.

‘It sounds heartless but my life is better now we’ve split and I’m back on full benefits. I do miss Paul and the kids are sad that we’ve broken up... I feel guilty but I know it’s for the best. Now I’m only going to date men on benefits – life’s much easier that way.’

Mr Burke told the magazine: ‘Portia’s very money-orientated and obsessed with sponging off the system. I’ve worked since I left school at 16 and I don’t want to live on benefits.

‘I was devastated when they split up – I just couldn’t see how they could move forward while living apart.

‘Now I’m happily single and focusing on the kids.’

A spokesman for the Taxpayers’ Alliance said: ‘It’s no surprise people are breaking up with their partners when there are financial incentives to do so. The benefits system is full of loopholes and allowances.

‘It’s clear radical reform is needed to make sure this sort of abuse doesn’t become even more widespread.’