Scientists at Duke University in North Carolina have achieved a significant breakthrough by decoding the genetic makeup of Akkermansia, a cutting-edge probiotic with potential metabolic and immunological benefits. Led by Dr. Raphael Valdivia, the research team uncovered a connection between this bacterium and its ability to regulate cholesterol biosynthesis, while also developing a system for manipulating Akkermansia muciniphila to enhance its health-boosting properties.
Dr. Valdivia expressed his excitement about the discovery, stating, “We are thrilled to reveal the potentially significant role of Akkermansia muciniphila in regulating cholesterol biosynthesis. This discovery opens up new avenues for engineering this probiotic microbe to enhance its health benefits and develop targeted interventions for metabolic disorders and immunological dysregulation.” Their groundbreaking findings have been published in the prestigious journal Nature Microbiology.
In an independent commentary published in the same journal, Dr. Federico Rey from the University of Wisconsin-Madison acknowledged the study’s major contribution, especially in the development of protocols and tools for transposon mutagenesis and sequencing in A. muciniphila, a potential candidate for preventing metabolic disorders. He also highlighted the research’s ability to define, at a high genetic resolution, the molecular mechanisms by which A. muciniphila degrades mucins, emphasizing its importance in a competitive environment.
Akkermansia, particularly the A. muciniphila species, has garnered increasing interest for its health-promoting effects. In rodents, treatment with A. muciniphila has shown promise in reducing obesity and related issues such as glucose intolerance, insulin resistance, and gut permeability. In humans, the abundance of A. muciniphila in the intestinal mucus layer is inversely correlated with BMI, type 1 diabetes, and bowel diseases. This bacterium also plays a crucial role in producing nutrients that support the intestinal mucus layer, helping to maintain a healthy intestinal barrier and control inflammation in the gut.
Notably, much of the research on A. muciniphila has been conducted at the Catholic University of Louvain in Belgium, with a spin-off company called A-Mansia focused on developing commercial products based on A. muciniphila.
Furthermore, Bloom Science, a clinical-stage company specializing in novel therapeutics for complex neurological disorders, is exploring the potential of Akkermansia, with Dr. Valdivia serving as a co-founder.
To achieve these groundbreaking findings, Dr. Valdivia and his colleagues collaborated with researchers at the University of California Berkeley, employing various techniques over a five-year research journey. Their methods included high throughput transposon mutagenesis, comparative genomics, and transcriptomics, which enabled them to identify key genes related to the growth and colonization of the gut.
Dr. Valdivia and Dr. Lauren Davey, the first author of the paper, shed light on the significance of their discoveries. They pointed out that much remains unknown about A. muciniphila’s biology, particularly regarding genes responsible for mucin transport and consumption. Nevertheless, their findings suggest a potential link between mucin metabolism by A. muciniphila and its regulation of host lipid homeostasis. This opens up the possibility of using this bacterium to modulate gene expression in colonic epithelia and enhance probiotic properties.
The research received funding from the US National Institutes of Health, the American Heart Association, and the Natural Sciences and Engineering Research Council of Canada, underscoring the importance of this groundbreaking work in advancing our understanding of Akkermansia and its potential benefits for human health.
