

Duke University School of Medicine researchers are the first to analyze the genetic makeup of Akkermansia, a gut bacteria that could aid in cholesterol management and be employed as a next-generation probiotic. This gut bacteria thrives in the intestine’s mucus layer and has an affinity for breaking down a type of sugary protein called mucin. This one-of-a-kind ability could be beneficial to our health.
When Akkermansia is present in sufficient numbers, it is linked to improved metabolic and immunological health. As a result, several scientists are investigating it as a probiotic.
However, they have had difficulties regulating its genes in the lab, which has impeded their understanding of how the bacterium works and how it may affect our health.
Duke scientists, together with colleagues from the University of California, Berkeley, reveal a groundbreaking five-year journey into genetically engineering this gut bacteria in a report published in Nature Microbiology.
Their research is the first to take a close look at the bacterium’s genetic makeup and how it destroys mucins to grow and settle in the gut.
The researchers, lead by senior study author Raphael Valdivia, PhD, were able to trace how the bacterium consumes mucin, revealing that it adheres to the bacterial cell surface and is transported into compartments within the cell in a precise manner.
The researchers identified many Akkermansia genes required for gut growth and colonization using a range of approaches including high throughput transposon mutagenesis, comparative genomics, and transcriptomics.
These genes encode proteins that aid the bacteria in the consumption of mucin, the production of fatty acids, and the regulation of metabolism.
“For a long time, we could not manipulate the genome of Akkermansia to understand what the function of its many genes are,”says Valdivia, who is a professor at the Department of Integrative Immunobiology at the Duke University School of Medicine.
He also added that “Most of the information within Akkermansia genome is unknown, it is only when you have the ability to knock each gene out individually and look at what the outcome is, that you can begin to understand how it grows, what kind of metabolites it makes, and how they may impact us.”
Investigating Gene Functions:
The Duke researchers discovered that Akkermansia can inhibit the activation of genes involved in the production of cholesterol in the gut, but only when it consumes mucins. This implies that Akkermansia forms a close relationship with us in which we feed it mucins and they help us manage cholesterol synthesis.
Cholesterol buildup can lead to heart disease, stroke, and other metabolic illnesses.
In a research briefing published in the journal, a professor of bacteriology, Federico Rey, PhD at the University of Wisconsin-Madison wrote “A major contribution of this study is the development of protocols and tools for sequencing Akkermansia – a potential candidate to prevent metabolic disorders,” He also added that, “There’s an astonishing amount of interesting and actionable data.”
In the future, researchers hope to capitalize on their discoveries by employing the bacteria as a platform for vaccine development and diving more into the bacterium’s connection with the nervous system and neurodegenerative illnesses like ALS.
The bacterium, however, is not without its difficulties. Its proclivity to weaken the mucus barrier may also contribute to gastrointestinal inflammation.
“While Akkermansia has immense potential, it’s about finding the right balance if we are to exploit its beneficial effects,” the Duke scientist mentioned.
The researchers are investigating how to manipulate the bacterium to reduce these hazards while enhancing its medicinal potential.
Dietary choices, like most things in gut health, can influence Akkermansia levels, from fasting to berry and grape eating. Scientists, on the other hand, are thrilled about its potential as a “live medicine,” or a therapeutic agent capable of delivering helpful molecules directly to the stomach.
Several firms, like Bloom Science, where Valdivia is a co-founder, are looking into incorporating Akkermansia into probiotics.
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