By Andrea McBeth, ND
Introduction
This month, I am excited to dive into what might be the most fascinating class of postbiotics: bile acids. Over the past few years, I’ve attended numerous lectures and read groundbreaking research on these incredible molecules. One study, in particular, caught my attention—it showed that bile acids, modified by gut microbes, were found in the brains of mice. This discovery led me to believe that these modified bile acids may play a crucial role in how ThaenaBiotic® works to promote health.
Often, we've wondered how the small concentrations of individual metabolites or postbiotics in ThaenaBiotic® could significantly impact human health. Much like herbal medicine, we believe that a complex mixture of molecules works together in synergy. In this intricate blend, small amounts of many vital components can enhance each other's effects. For example, while butyrate alone isn't the whole story, the combined mixture of postbiotics from our healthy donors has a powerful impact beyond just one or two elements. Recent research by Pieter Dorrestein at UCSD, along with earlier studies, suggests that bile acids might be a key player in human health. Even in low concentrations, these bile acids can have significant functional relevance.
The most exciting part of this discovery is how it ties together years of research into the bile acid postbiotics. Last month, at the American Gastroenterology Association's annual Digestive Disease Week (DDW) conference in Washington, D.C., I attended a lecture that truly connected all the dots. I texted my friend while coordinating lunch, saying, "I’m awake now. I just heard the most fascinating bile acid presentation - this might be one of the best microbiome conferences I’ve ever been to!" It felt like history was being made right before my eyes. The title of the talk, "Impact of Diet On Microbial Metabolites," didn’t convey the full magnitude of the work. Ipsita Mohanty, presenting as part of the Dorrestein Lab, summed it up perfectly: bile acids could be the communication messengers of the body. Acting as the mail carriers of the gut microbiome, using our evolutionary history of refined chemistry to deliver highly specialized bacterial-conjugated molecules to specific regions and tissues.
Why is this so important to us at Thaena? If these bile acid conjugates only need pico or nanomolar concentrations to be guided to specific regions of the brain, muscle, bone marrow, thyroid, or any other tissue, then the concentrations from our healthy donors in the body and subsequently in the blood of our recipients might matter more than we ever imagined.
Mohanty's theory posits that the basic structures of bile acids are specific to certain tissue receptors. Once there, they deliver conjugates that can change tissue behavior, act as energy sources, or alter gene expression. Imagine glycine, cysteine, ornithine, or any number of diverse bile acid conjugates being delivered with high affinity, impacting the whole system. Then, consider what happens in our guts when these highly specific bile acids cannot be made due to missing precursors or the loss of bacteria with the right enzymes because of antibiotics, dysbiosis, or disease. If our brain, muscle, or other tissue is missing a key nutrient or signaling molecule, this could be a major factor in how our microbiome impacts disease. !!!
From Fat Digesters to Metabolic Powerhouses
When we first learned about bile acids in biology class, they were – more or less – relegated to the simple role of fat digesters. Produced in the liver from cholesterol, these molecules were known for their ability to break down dietary fats. Fast forward a few decades, we now know that bile acids are like Swiss Army knives – multifunctional and essential for much more than just digestion. Pioneers like Pieter Dorrestein have blown the lid off our traditional understanding. Thanks to advanced techniques like reverse metabolomics, Dorrestein and his team have uncovered thousands of bile acids with roles that extend far beyond the gut. Their groundbreaking research has shown us that these molecules are key players in regulating our metabolism, immune system, and even our brain function.
Microbial Magic
One of the most fascinating discoveries published by Dorrstien’s lab is how our gut microbiota – those trillions of bacteria living in our intestines – modify bile acids. These microbes transform primary bile acids into a variety of secondary bile acids, creating a whole new world of biologically active compounds. It's like having a personal chemist in our gut, constantly tweaking these molecules for optimizing our health.
The microbial modification process of bile acids involves adding amino acids, hydroxyl groups, and other chemical structures to the bile acids. The result? A diverse array of microbially conjugated bile acids that play critical roles in our health. These modified bile acids can regulate everything from our immune response to our metabolic processes.
The Signaling Superstars
Bile acids aren't just passive bystanders; they're active messengers, communicating with our cells through specific receptors like FXR and TGR5. These interactions help regulate metabolic homeostasis, glucose and lipid metabolism, and inflammatory responses. In simpler terms, bile acids help keep our body's internal balance in check. For instance, certain bile acids can promote the development of regulatory T cells (Tregs), which are crucial for controlling inflammation. This is especially important for conditions like inflammatory bowel disease (IBD), where reducing inflammation can significantly improve symptoms and quality of life.
Health and Disease
The implications of these discoveries related to bile acids are huge. They are now being linked to a variety of health conditions, including nonalcoholic fatty liver disease, irritable bowel syndrome (IBS), colorectal cancer, and even neurological disorders like Parkinson's and Alzheimer's. For example, in patients with Crohn's disease, specific bile acids produced by gut bacteria can help modulate immune responses, potentially offering new avenues for treatment. The same goes for metabolic conditions like diabetes, where bile acids influence insulin sensitivity and energy expenditure. Needless to say, bile acids are proving to be essential biomarkers and potential therapeutic targets.
ThaenaBiotic® and the Future
What does this mean for ThaenaBiotic®? Our product is designed to harness the natural powers of a healthy microbiome. By promoting the production of beneficial bile acids, we believe ThaenaBiotic® can help restore balance to the gut microbiome thereby improving overall health.
Imagine being able to influence these powerful molecules to enhance immune function, reduce inflammation, and regulate metabolism?! That's the potential we're looking at with ThaenaBiotic®, and it goes beyond gut health and becomes about holistic well-being more generally – all influenced by the incredible capabilities of bile acids.
Conclusion
Bile acids have evolved from being seen as simple molecules for fat digestion to being recognized as powerful signaling molecules with wide-ranging effects on health and disease. The groundbreaking research by Pieter Dorrestein and others has expanded our understanding, revealing the complex and critical roles of these molecules. ThaenaBiotic® is at the forefront of leveraging these insights to improve health outcomes, highlighting the transformative potential of bile acids in modern medicine. Stay tuned for more exciting discoveries in this rapidly evolving field - if you could not tell, I LOVE this work and I LOVE bile acids!
You can check out Pieter Dorrstein's presentation here on YouTube.
References
- Mohanty, I., Allaband, C., Mannochio-Russo, H., El Abiead, Y., Hagey, L. R., Knight, R., & Dorrestein, P. C. (2024). The changing metabolic landscape of bile acids - keys to metabolism and immune regulation. Nature Reviews. Gastroenterology & Hepatology. https://doi.org/10.1038/s41575-024-00914-3
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