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Biotechnology and Bioengineering

Gut Microbes Unleash Cancer-Fighting Bile Acids with Anti-Androgen Properties

Bacteria naturally present in the human intestine (known as the gut microbiota) can transform cholesterol-derived bile acids into powerful metabolites that strengthen anti-cancer immunity by blocking androgen signaling, according to a preclinical study.

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Gut bacteria have long been known to play a crucial role in our overall health and well-being. These tiny microorganisms reside in our intestines and are responsible for breaking down food, regulating our metabolism, and even influencing our mood. But did you know that these gut microbes can also produce powerful cancer-fighting molecules? A recent study has made this astonishing discovery, and it could potentially revolutionize the way we approach cancer treatment.

Researchers at Weill Cornell Medicine have found that certain types of bacteria in the gut can transform cholesterol-derived bile acids into potent anti-cancer agents. These modified bile acids are capable of blocking the activity of a molecule called the androgen receptor, which plays a crucial role in regulating cell growth and development. By inhibiting this receptor, these cancer-fighting molecules can help prevent the spread of tumors and even trigger their destruction.

The study was led by Dr. Chun-Jun Guo, an associate professor of immunology at Weill Cornell Medicine, who said that he was “very surprised” by the findings. The researchers tested over 100 different bile acid molecules modified by gut bacteria and discovered three specific compounds that were capable of blocking the androgen receptor.

When these modified bile acids were administered to mice with bladder cancer, they were found to induce a potent anti-tumor response. Further analysis revealed that the bile acids specifically boosted the activity of T cells, the immune cells best equipped to kill cancer cells.

The researchers believe that this discovery could lead to new approaches for treating various types of cancers, including breast, prostate, and lung cancer. They suggest introducing targeted gut microbes to patients before therapy or directly administering the anti-cancer bile acids as part of treatment.

However, important questions remain unanswered. How might diet influence microbiota composition and affect the production of these beneficial molecules? What physiological effects might these modified bile acids have in healthy individuals?

The researchers are now focused on precisely controlling the synthesis and release of these beneficial molecules using advanced techniques to genetically engineer gut commensal bacteria. They aim to understand the broader physiological impact initiated by these androgen-blocking, microbiota-derived bile acids.

This breakthrough has opened up exciting new possibilities for cancer treatment, and it highlights the profound partnership between the human host and its gut microbiota. By integrating microbial activity into the design of future therapies, researchers may be able to unlock new ways of harnessing the power of our gut microbes to promote overall health and well-being.

Biochemistry

Unraveling Nature’s Secret: How Velvet Worm Slime Could Revolutionize Sustainable Materials Design

A new discovery about the slime ejected by velvet worms could revolutionize sustainable material design. The findings outline how a naturally occurring protein structure, conserved across species from Australia, Singapore and Barbados over nearly 400 million years of evolution, enables the slime’s transformation from liquid to fiber and back again. It’s a discovery that could inspire next-generation recyclable bioplastics.

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The discovery of the remarkable properties of velvet worm slime has sent shockwaves through the scientific community, offering new hope for sustainable material design. Researchers from McGill University have made a groundbreaking find that could lead to the development of next-generation recyclable bioplastics.

Velvet worms, small caterpillar-like creatures found in humid forests of the southern hemisphere, possess an extraordinary ability – their slime can transform from liquid to fibre and back again. This remarkable property has puzzled scientists for centuries, but a team led by Matthew Harrington, a chemistry professor and Canada Research Chair in green chemistry, has finally decoded the molecular structure behind this phenomenon.

Using protein sequencing and AI-driven structure prediction (AlphaFold), the researchers identified previously unknown proteins in the slime that function similarly to cell receptors in the immune system. These receptor proteins appear to link large structural proteins during fibre formation, enabling the slime’s remarkable reversibility.

The implications of this discovery are profound. Traditional plastics and synthetic fibres require energy-intensive processes to manufacture and recycle, often involving heat or chemical treatments. In contrast, the velvet worm uses simple mechanical forces – pulling and stretching – to generate strong, durable fibres from biorenewable precursors, which can later be dissolved and reused without harmful byproducts.

While a plastic bottle that dissolves in water may seem like an impractical solution, Harrington believes that adjusting the chemistry of this binding mechanism could overcome this limitation. The team’s next challenge will be to experimentally verify the binding interactions and explore whether the principle can be adapted for engineered materials.

The study was co-authored by researchers from McGill University and Nanyang Technological University (NTU) in Singapore, highlighting the importance of international collaboration in addressing pressing global challenges.

As Harrington aptly puts it, “Nature has already figured out a way to make materials that are both strong and recyclable. By decoding the molecular structure of velvet worm slime, we’re now one step closer to replicating that efficiency for the materials we use every day.”

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Bacteria

“Unlocking TB Diagnosis: New Molecular Label Could Lead to Simpler, Faster Tests”

Chemists found a way to identify a complex sugar molecule in the cell walls of Mycobacterium tuberculosis, the world’s deadliest pathogen. This labeling could lead to simpler, faster TB tests.

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The world’s deadliest infectious disease, tuberculosis (TB), claims over 1 million lives annually. Despite advancements in diagnosis and treatment, TB remains a significant challenge, particularly in developing nations where access to chest X-rays and molecular diagnostics is limited. Current diagnostic methods often have high false negative rates and require extensive sample preparation, delaying diagnosis.

MIT chemists have developed a breakthrough approach using an organic molecule that reacts with specific sulfur-containing sugars found only in three bacterial species, including Mycobacterium tuberculosis (Mtb), the microbe responsible for TB. By labeling a glycan called ManLAM using this small-molecule tag, researchers can now visualize where it is located within the bacterial cell wall and study what happens to it throughout the first few days of tuberculosis infection.

The research team led by Laura Kiessling, Novartis Professor of Chemistry at MIT, aims to use this approach to develop a diagnostic that could detect TB-associated glycans in culture or urine samples. This would provide a cheaper and faster alternative to existing diagnostics, making it more accessible to developing nations where TB rates are high.

Using their small-molecule sensor instead of antibodies, the researchers hope to create a more sensitive test that can detect ManLAM in the urine even when only small quantities are present. This has significant implications for TB diagnosis and treatment, particularly for patients with very active cases or those who are immunosuppressed due to HIV or other conditions.

The research was funded by the National Institute of Allergy and Infectious Disease, the National Institutes of Health, the National Science Foundation, and the Croucher Fellowship. The findings have the potential to revolutionize TB diagnosis and improve patient outcomes worldwide.

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Bacteria

A Game-Changing ‘Treasure Chest’ for Targeted Gut Treatment: Delivering Medicine Directly to the Lower Gut

A new approach to drug design can deliver medicine directly to the gut in mice at significantly lower doses than current inflammatory bowel disease treatments. The proof-of-concept study introduced a mechanism called ‘GlycoCaging’ that releases medicine exclusively to the lower gut at doses up to 10 times lower than current therapies.

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The discovery of a new approach to drug design, called GlycoCaging, has opened up promising possibilities for targeted treatment of inflammatory bowel disease (IBD) in humans. This innovative technique involves releasing medicine directly into the lower gut at significantly lower doses than current therapies.

Researchers from the University of British Columbia (UBC) have developed this mechanism, which relies on specific bacteria residing in the human gut to unlock the “treasure chest” containing the medicine. By bonding a molecule to a steroid, the researchers have created a system that can deliver potent drugs directly to the inflamed areas of the gut.

According to Dr. Harry Brumer and Dr. Laura Sly, co-senior authors of the study published in Science, this technique has the potential to revolutionize the treatment of IBD, which affects an estimated 322,600 Canadians as of 2023. The current treatments for IBD often come with serious side effects, including osteoporosis, high blood pressure, diabetes, and negative mental health outcomes.

Using mice models of IBD, the researchers demonstrated that GlycoCaging can deliver medicine at doses up to 10 times lower than non-caged versions while achieving the same anti-inflammatory effects. The study showed that the drug was targeted exclusively to the gut, with minimal absorption in other areas of the body.

The potential for human treatment is promising, as the research team found that all people had the ability to activate the drugs using the GlycoCaging system, even those with IBD. Moreover, the majority of participants had genetic markers indicating their ability to use this system.

While more advanced animal trials and human clinical trials are needed to further validate the efficacy and safety of GlycoCaging, this innovative approach has the potential to transform the treatment of IBD and other gut-related disorders. The UBC researchers have patented the technology, paving the way for future development and implementation in humans.

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