#283 ‒ Gut health & the microbiome: improving and maintaining the microbiome, probiotics, prebiotics, innovative treatments, and more | Colleen Cutcliffe, Ph.D.
Colleen Cutcliffe, expert in molecular biology and co-founder of Pendulum Therapeutics, discusses the complexity of the microbiome, the role of probiotics and prebiotics, the importance of a high-fiber diet, the potential of fecal microbiota transplant (FMT), and the challenges in manufacturing and maintaining bacteria strains. She also explores the role of acromancia in the gut microbiome, the efficacy of probiotics in improving GI symptoms, and the impact of high fiber and high polyphenol foods on gut health.
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Quick takeaways
Fecal microbiome transplants (FMT) are a highly successful treatment for Clostridium difficile infections, but concerns about safety and regulation need to be addressed.
The gut microbiome relies on the metabolism of insoluble fibers, such as butyrate, for gut health, which can be supplemented through diet or capsules.
The human microbiome, including the gut microbiome, is influenced by factors like birth delivery method, diet, and antibiotics, with ongoing research to understand its roles and functions.
Microbiome research faces challenges in measurement methods, delivery techniques for interventions like FMT, and understanding the impact on disease and metabolism.
The gut-brain connection through the microbiome can affect food cravings and behavior due to the microbiome's ability to generate neurotransmitters.
The vaginal microbiome plays a role in maintaining a healthy environment and changes in it can lead to conditions like bacterial vaginosis, increasing the risk of preterm labor.
Deep dives
Fecal Microbiome Transplants and C. Difficile
Fecal microbiome transplants (FMT) have proven to be a highly successful treatment for Clostridium difficile infections. C. difficile is a strain of bacteria that can thrive when other bacteria in the gut are wiped out by antibiotics. FMT involves transplanting feces from a healthy donor into the gut of an infected individual, restoring a healthy balance of bacteria and resolving the infection. While FMT has a success rate of nearly 99%, concerns have been raised about the safety and regulation of the procedure. The source of the donor feces and potential transfer of pathogens or unintended changes to the recipient's metabolism are points of caution that need to be addressed.
Carbohydrate Metabolism and Short-Chain Fatty Acids
The gut microbiome plays a crucial role in the metabolism of carbohydrates, particularly insoluble fibers. Certain strains of bacteria, such as Clostridial and Bifidobacterium species, metabolize these fibers and produce short-chain fatty acids like butyrate. Butyrate is essential for gut health and is utilized by the colon cells as a source of energy. A lack of butyrate has been associated with colon health issues, including colon cancer. While insoluble fibers are found in vegetables and fruits, supplementing with fiber in powder or capsule form can also have a positive impact on the microbiome, though delivery methods and maintaining diversity remain important considerations.
Understanding the Human Microbiome
The human microbiome refers to the diverse community of microbes, including bacteria, viruses, fungi, and yeast, that resides in and on our bodies. The microbes in the microbiome are primarily found in the gut, skin, nasal passages, and lungs. The gut microbiome, in particular, is of great interest due to its impact on overall health. Factors such as birth delivery method, diet, and exposure to antibiotics can influence the composition and diversity of the microbiome. Understanding this complex ecosystem is an ongoing endeavor, and ongoing research aims to elucidate the roles and functions of different microbial strains and their interactions with the human host.
Regulation and Challenges in Microbiome Research
The field of microbiome research faces challenges in terms of regulation, measurement methods, and understanding the impact of microbial strains and functions. While techniques like shotgun sequencing and QPCR can provide insights into the composition and abundance of microbes, longitudinal studies are needed to capture the dynamic nature of the microbiome. Delivery methods for interventions such as fecal microbiome transplants (FMT) are still being refined, and ensuring the safety of donors and recipients remains a priority. Additionally, the microbiome's influence on metabolism and disease requires further investigation to fully realize its potential in healthcare.
The influence of the microbiome on food cravings and behavior
The gut-brain connection through the microbiome can influence food cravings and behavior. The microbiome's ability to generate neurotransmitters can impact cravings and change behavior.
The impact of antibiotics and other factors on the microbiome
Antibiotics and factors like aging, intense stress, and disrupted circadian rhythm can deplete the microbiome and lead to loss of specific strains and functions.
The role of the microbiome in vaginal health and pregnancy
The vaginal microbiome plays a role in maintaining an acidic and healthy environment. Changes in the microbiome can lead to conditions like bacterial vaginosis, which can increase the risk of preterm labor.
Understanding the challenges and potential of probiotics
Probiotics, such as lactobacillus and bifidobacterium, are commonly used, but their effectiveness can vary depending on the strain, manufacturing process, and individual factors. The current focus is on developing reproducible and effective probiotics that can address specific health needs.
Freeze-dried Acromancia: Capsules for Dormancy and Stability
Acromancia, a strain of bacteria, can be freeze-dried and put into capsules to maintain dormancy and stability. The freeze-dried state allows the bacteria to be stored at room temperature or in the refrigerator. When water enters the capsule, the bacteria come back to life, and oxygen causes their eventual death. To ensure stability, desiccant packets are included with the freeze-dried capsules. The time required for the freeze-drying process varies for different strains of bacteria.
Manufacturing Process and High-Touch Anaerobic Methods
The manufacturing process for Acromancia capsules involves an intense anaerobic environment. The process was developed by PhD scientists and microbiologists in San Francisco, and involves custom-built anaerobic chambers. The process requires working with gloves and using a special deoxygenated box for samples. The high-touch nature of the manufacturing ensures the quality and viability of the capsules.
The Impact of Acromancia on Blood Glucose Control
Acromancia has been found to play a role in controlling blood glucose levels through the GLP1 pathway. Acromancia stimulates L cells in the gut microbiome to secrete GLP1, which helps regulate insulin secretion and induce satiety. Acromancia can bind to specific receptors and produce short-chain fatty acids, such as propionate, which further stimulate GLP1 secretion. Clinical trials with Acromancia capsules have shown promising results in lowering A1C levels and reducing blood glucose spikes.
Clinical Trials and Future Research
Clinical trials with Acromancia capsules have demonstrated their efficacy in lowering A1C levels and reducing blood glucose spikes in people with type 2 diabetes. Ongoing research aims to explore the potential benefits of Acromancia in other areas, such as bipolar disorder, and investigate its effects on other health outcomes. The company is also exploring the use of other strains and conducting pilot studies to evaluate their impact on cravings and other health markers. Future studies will continue to shed light on the role of Acromancia and other strains in improving health and metabolism.
Colleen Cutcliffe is an expert in molecular biology and co-founder of Pendulum Therapeutics, a company working to develop treatments for a variety of diseases by targeting the microbiome. In this episode, Colleen delves into the complexity of the microbiome, how it is tested, and how it changes over time. She explores how probiotics, prebiotics, and postbiotics affect the gut and makes a compelling case that well-developed products have the potential not only to enhance gut health but also to positively influence overall metabolic well-being. Colleen emphasizes the significance of a high-fiber diet in sustaining a thriving gut microbiome, shares insights on minimizing microbiome damage during antibiotic use, provides tips for fostering and preserving a healthy gut, and much more.
We discuss:
Colleen’s background and current focus [4:45];
The basics of the microbiome [7:15];
The study of the human microbiome [15:15];
Categories of bacteria, and the implications on health of the rapid evolution of bacteria [19:45];
Methods for measuring and understanding the microbiome, and key indicators of microbiome health [28:30];
The important role of fiber for promoting gut health through the production of butyrate [38:30];
The case for manipulating gut bacteria via fecal microbiota transplant (FMT) [45:00];
Dynamics of the microbiome: the gut-brain connection and how antibiotics, nutrition, stress, and more impact the microbiome's diversity and function [50:15];
Factors that influence the vaginal microbiome [55:15];
The effect of gut microbes on obesity and challenges with fecal transplants in people [58:45];
Beneficial strains of gut bacteria and strains commonly found in probiotics [1:01:15];
The difference between a probiotic and prebiotic, and how CFUs are a measure of the “active ingredient” [1:09:45];
Considerations about how probiotic strains are produced, and more on the meaning of CFU [1:14:15];
Mitigating the effect of antibiotics on the microbiome [1:22:30];
What do we know about the effect of artificial sweeteners on the gut microbiome? [1:30:00];
Why Akkermansia is a keystone strain with implications for metabolic health and an individual’s response to dietary interventions [1:36:15];
The essential steps necessary to develop a robust probiotic for optimal health support [1:45:45];
How Akkermansia helps control blood glucose, and potential implications of Akkermansia in weight loss, diabetes management, and more [1:48:45];
Pendulum Therapeutics’ commitment to rigorous product develop [2:06:30];
Details about the probiotic “Glucose Control” and other probiotics developed by Pendulum Therapeutics [2:13:00];
Further studies of Akkermansia that have been proposed or are underway [2:20:30]; and
