Tag Archives: gut

Changes in Gut Microbiome Associated with MS Treatment

March 24, 2020

As the most widespread disabling neurological condition in young adults, multiple sclerosis (MS) affects approximately 1 million people in the United States and up to 2.3 million across the globe. Although researchers have not yet discovered the underlying causes of the condition or the reasons behind its unpredictable progression, there is an increased focus on the role of the gut microbiome in its development.

Prior research linking gut flora and multiple sclerosis has shown differences in the types of gut bacteria found in individuals with multiple sclerosis (MS). Patients with MS tend to have more archea –  a microbe responsible for inflammation – and less butyricimonas – a microbe with anti-inflammatory properties – compared with individuals without the condition.

New research implicates that patients with multiple sclerosis exhibit changes in gut bacteria composition after being treated with the disease-modifying drug ocrelizumab (Ocrevus).

Effect of Medication on Gut Microbiome

Disease-modifying medications tackle MS by depleting B cells, leading researchers to hypothesize that ocrelizumab could normalize the phenotype and metabolic profiles of gut bacteria thereby promoting an anti-inflammatory immune environment. As part of the ongoing trial, the research team is enrolling patients with new-onset multiple sclerosis and evaluating longitudinal samples of paired blood and stool with advanced techniques – including IgA-Seq, a novel tool that allows the differentiation of immune-reactive bacteria from IgA-uncoated bacteria.

Changes in Gut Bacteria

According to preliminary findings from the ongoing study, the normalization of certain components of the fecal microbiome in MS patients occurred at 1 month after ocrelizumab treatment, compared with baseline measurements. The team’s initial results are based on a cohort of 8 patients with MS and 5 control group participants.

Several members of the MS group showed very high IgA-coated indices for selected bacteria in the butyrate-producing Lachnospiraceae family at baseline. Following ocrelizumab treatment, these patients showed a reduction in the IgA coating index for butyrate producers. Furthermore, butyrate was significantly decreased at baseline in the MS group compared with levels found in the healthy control group. However, these changes did not last and the difference in butyrate levels dissipated after treatment was ceased. No differences were observed in acetate and propionate values.

Implications of Bacteria Changes

“Our data suggest that a subset of butyrate-producing gut bacteria is recognized as pathogenic by the immune system of untreated MS patients, based on high levels of IgA coating,” the researchers told Medscape Medical News, “This phenomenon could impact the amount of butyrate produced and affect the differentiation of circulating immune cells.”

The reduction of the IgA coating index of butyrate-producing bacteria as a result of ocrelizumab treatment points to its potentially significant role in the efficacy of B-cell depletion in MS patients. “The data also suggest that “changes in the gut microbiota may comprise part of the mechanism of action for a variety of MS disease-modifying therapies, including ocrelizumab,” lead author Erin Longbrake, MD, PhD told Medscape Medical News.

Due to the small scale of the study, its results are difficult to generalize; however the preliminary findings add to a growing body of evidence supporting the critical relationship between the gut microbiome and multiple sclerosis pathology. The research team is currently enrolling additional participants to investigate this connection further and plans on expanding its analysis to include long-amplicon sequencing and metabolomic analysis.

With about 200 new cases of multiple sclerosis diagnosed per day in the United States, there is an acute need for a better understanding of its underlying mechanisms. Identifying how these changes in the gut microbiome occur and improving the understanding of the implications of pharmacologic therapies could lead to the development of more targeted, personalized interventions aimed toward correcting specific pathologic modifications.

Parkinson’s Disease: Origins in the Gut?

January 15, 2018

Within the last few weeks, researchers at Mount Sinai have found strong correlations between Parkinson’s disease and the gut, confirming earlier studies that indicate the association.

A new genetic study demonstrates that several variants in the LRRK2 gene raise or lower risk not only for Parkinson’s, but also for Crohn’s disease: an inflammatory bowel disorder. The researchers identified a new functional risk variant, N2081D, which increases LRRK2’s kinase activity, in addition to a protective variant that inactivates lRRK2. The study’s researchers confirm that these findings may provide insight into underlying disease mechanisms, and point toward improved therapeutic approaches: LRRK2 inhibits being developed for Parkinson’s may help people with Crohn’s, while anti-inflammatory approaches could likewise benefit Parkinson’s patients.

Moreover, an earlier study published in Neurology, the official journal of the American Academy of Neurology, investigates the role of the vagus nerve in Parkinson’s disease–suggesting that a resection of the nerve might stop or delay the spreading of Parkinson’s disease, and providing further concrete evidence of the link between Parkinson’s and the gut.

Historically cited as the pneumogastric nerve, the theory suggests that the vagus nerve might serve as the channel for transporting the protein alpha-synuclein from stomach to brain, where it forms ‘telltale clumps in Parkinson’s sufferers.’

If accurate, the hypothesis points to a clear origin of the neurodegenerative brain disorder: the gut. Moreover, it would explain and confirm the critical importance of the enigmatic protein, whose exact role in Parkinson’s has previously not been well understood.  Perhaps most importantly, it would point to a potential way to block the development and progression of Parkinson’s: a surgical procedure known as a vagotomy, which is generally used in people with severe gastric ulcers, and involves cutting the vagus nerve in order to completely sever the ‘pathway from gut to brain.’

The objective of the published research was to examine whether vagotomy decreases the risk of Parkinson’s. Using comprehensive data from nationwide Swedish registers, the authors conducted a matched-cohort study of 9,430 vagotomized patients and 377,200 non-vagotomized patients. The researchers were aiming to find if the process of a vagotomy—in addition to a treatment for peptic ulcers—might lower the risk of Parkinson’s by blocking the route of alpha-synuclein to the brain.

After analyzing the data and assessing the subset of patients who received the most drastic version of the procedure, a truncal vagotomy—which removes the vagus nerve from contact with the liver, stomach, pancreas, gall bladder, small intestine, and proximal colon—they found that Parkinson’s disease was 22% less common than it was amongst people in the non-vagotomized comparison group.

While this study delivers clear epidemiological evidence to support the theory that Parkinson’s originates in the gut, previous studies further indicate that this may indeed be true. Alpha-synuclein protein clumps have been detected in the guts of patients with very early-onset Parkinson’s; in mice who had alpha-synuclein from the brains of human Parkinson’s patients implanted in their intestinal walls, researchers have seen movement of those proteins in the vagus nerve.

Our upcoming 26th Annual Spring Congress will focus on brain diseases and disorders, including the prevalence of Parkinson’s disease and related conditions. Our Module IV: Gastroenterology will also spotlight the gut-brain axis, and discuss the strong correlation between the gut microbiome and brain conditions.

The Link Between Parkinson’s & Gut Bacteria

November 8, 2017

Recent findings have confirmed a long assumed, yet never officially proven, hypothesis regarding a functional link between the gut’s bacteria and the onset of Parkinson’s disease. While previous research has demonstrated strong correlations between the gut and the disease, no research has shown the exact relationship.

One of the world’s most prevalent neurodegenerative disorders, Parkinson’s affects approximately 1 million people in the United States. A progressive and chronic movement disorder, Parkinson’s involves the malfunction and ultimate death of the brain’s vital nerve cells: neurons. As the neurons that typically produce normal levels of dopamine—the chemical that communicates with the segment of the brain that controls coordination and movement—regularly decrease and dopamine levels lessen, a person becomes unable to control movement. Worsening symptoms include the gradual deterioration of motor symptoms: body tremors, bradykinesia/slowness of movement, rigidity, and severe postural instability.

The studies suggest a new, unprecedented way of treating the disease and its symptoms: targeting the gut, rather than the brain, and developing next-generation probiotics: a more sophisticated version than those readily available for purchase and consumption today.

Through conducting trials during which mice were fed certain short-chain fatty acids that are commonly produced by bacteria in the gut, in addition to actual samples of gut bacteria from human Parkinson’s patients and healthy human controls, the team found that the mice either exhibited symptoms, or did not produce symptoms, respectively. The team’s researchers expressed their hope in the possibility of the prescription of drugs that contain bacteria to prevent Parkinson’s, or treat the disease symptoms. Moreover, the studies imply that Parkinson’s is less related to hereditary genetics than environmental factors—including the onset of age.

At A4M, our overarching goal is to treat—and ultimately prevent—the onset of diseases associated with aging. Attend our upcoming events and learn about the advancement of technology and biomedical engineering, coupled with the most recent research & inquiries into methods that optimize the human aging process.
 
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