New Clues to Chronic Diseases Turn Up in the Gut

The microbiome may hold keys to myriad ailments. In 2023, a trio of studies heralded potential breakthroughs.

By Kenneth MillerDec 11, 2023 9:00 AM
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(Credit: ArtemisDiana/adobe Stock.icons: Rvector/shutterstock)


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It’s no secret that our gut microbiomes — the trillions of bacteria, viruses and fungi that inhabit our gastrointestinal tracts — play a vital role in our lives. In the past decade, researchers have found that these microorganisms help us perform an array of bodily functions and, notably, that they can profoundly affect our mental health.

Still, we’re only beginning to learn how those interactions work, and how they might be harnessed to treat or prevent disease. In a study published in February 2023 in PLOS Biology, for example, researchers at the University of Virginia found that a protein called aryl hydrocarbon receptor, or AHR, which regulates immune cells’ response to chemicals produced by the gut microbiome, may play an important role in multiple sclerosis (MS). The disease causes the immune system to attack myelin, the insulation around nerve fibers, prompting symptoms that can include muscle weakness, pain, and vision loss.

When the team induced MS in genetically engineered mice whose immune systems lacked AHR, they recovered quickly after only a brief bout of paralysis. The reason, the team determined, was that their guts contained higher levels of bile acids, which would normally be broken down by gut microbes. The acids, in turn, weakened the animals’ T cells — immune-system warriors that go rogue in autoimmune disorders. When gut microbiota from AHR-free mice were transplanted into normal mice with MS, they recovered, too.

These findings could point to improved treatments for the 2.8 million people with MS worldwide, suggests lead author Andrea Merchak. Currently, the only approved drugs are immunosuppressants, which put patients at risk of infection and troublesome side effects.

Merchak and her team are now testing medications that modify bile acids on mice with MS. Such microbiome-based therapies, she believes, might be able to ward off the disease’s ravages without the downsides of immunosuppressants. “If we can slow the progression and prevent lasting damage,” she says, “these patients can live longer and fuller lives.”

Investigating Further

Parkinson’s disease, a neurodegenerative disorder characterized by tremors, muscle rigidity and dementia, impacts an estimated 8.5 million people globally. It’s associated with clumps of misfolded alpha synuclein proteins that accumulate in patients’ brains. But these clumps have also been found in patients’ intestinal nerves a decade or two before Parkinson’s symptoms occur, leading to the theory that resident microbes may cause the aggregation that then travels to the brain.

Researchers at the University of Helsinki in Finland have been investigating the possible role of the bacterial species Desulfovibrio (DSV) in Parkinson’s. Over the past two years, they’ve found that DSV is more common in people with the disease, and that the quantity of the bacteria correlates with the severity of symptoms. In a new study, published in May in Frontiers in Cellular and Infection Microbiology, the team examined those links in more detail. They recruited 20 participants, half with Parkinson’s and half without. Each subject provided fecal samples, which were analyzed for the presence of DSV. Strains of the bacteria found in both groups were fed to tiny C. elegans worms, whose heads were then examined under a microscope.

The researchers found that worms fed DSV from Parkinson’s patients had more and larger alpha-syn aggregates than worms fed DSV from healthy individuals or a control group that was fed E. coli. Worms fed Parkinson’s patients’ DSV strains also died in greater numbers.

These findings indicate that specific strains of Desulfovibrio bacteria are a “likely” cause of Parkinson’s, Saris says, though other factors are also involved. “The precautionary principle suggests that for patients, it would be good to get rid of those strains, or at least reduce them.” He and his team are currently investigating methods — including antimicrobial peptides and dietary regimens — that might be able to do just that.

Seeing Improvement

Meanwhile, also in May, researchers from the Chinese University of Hong Kong reported encouraging news on long COVID: A daily capsule containing live intestinal bacteria was effective in relieving several of the syndrome’s key physical and mental symptoms.

The treatment, known as SIM01, comprised three Bifidobacteria species along with prebiotic substances to help support their growth. Earlier studies, led by gastroenterologist Siew Ng, had found a depletion of beneficial gut bacteria in COVID-19 patients — and that SIM01, a cocktail of such microbes, reduced pro-inflammatory cytokines and promoted anti-SARS-CoV-2 antibody development.

For the current study, a team led by Ng’s doctoral student Raphaela Iris Lau enrolled 463 patients who had confirmed COVID-19 at least four weeks previously and who had at least one of 14 long COVID symptoms — which can include chronic pain, shortness of breath, loss of taste or smell, and other ills. Half received SIM01, and half received a placebo.

Those in the SIM01 group, the researchers found, were more likely than controls to see improvements in digestive problems, fatigue, difficulty concentrating, memory impairment and “general unwellness.” In the latter category, 77 percent said they felt better after six months with SIM01, compared to 59 percent of those on placebo. Results were similar for the other four symptom categories, with improvement rates ranging from 42 to 70 percent.

“What we found really fascinating was that probiotic use could treat neuropsychiatric symptoms in many long COVID patients, not just digestive ones,” says Lau. “We think that’s a breakthrough.”

This story was originally published in our January February 2024 issue. Click here to subscribe to read more stories like this one.

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