By Andrea McBeth, ND

If you missed Part I of the Thaena® origins story, you can find it here.

A Fantastical Journey
Through the Microbiome, Part II:
How ThaenaBiotic® Evolved 

Like all good adventures, creating ThaenaBiotic® took a few years of blood, sweat, tears, and - of course - lots and lots of poop. Looking at our arduous journey, we are often asked why we didn't just use individual postbiotic compounds like butyrate or heat-killed probiotics like Lactobacillus strains that can be cultured at scale. Our answer is rooted in the belief that the complexity of a healthy gut microbiome allows the bacteria and their molecules to act synergistically in ways we don't yet fully understand. Although humans have been studying organ systems that we can see like the brain and heart for hundreds of years, we didn’t appreciate the microbiome's existence nevermind its significance until about 20 years ago. 

The reason we believe it is not feasible yet to simply create cultured feces using probiotic strains becomes apparent when we draw a comparison with human blood. Scientists have been trying to synthesize blood for a long time without much success (unless you are reading vampire fantasy books). This is because, similar to poop, there are many components of these complex mixtures we still do not understand. So, in true scientific spirit, we accepted that we really knew nothing, and decided to trust our instincts and maintain the complexity of this unknown poop mixture in donor stool. 

We iteratively developed a sterilization process, changing one variable at a time, moving towards an end product that eliminated potential pathogens from stool but retained the important metabolites or postbiotics. This approach led us to step one: autoclave (sterilize with heat and pressure) our donor stool. A lot of people thought we were crazy (and many still do). But, as time has gone on, this crazy idea born in 2018 over beers in San Francisco has turned out to be less crazy than it seemed initially. As a growing body of evidence is published on how heat-killed probiotics and postbiotics can impact health, we are excited to have made the leap into the unknown. 

Historical Context: Pasteurization & its Impact

As we embarked on this journey with ThaenaBiotic®, it became increasingly clear that our approach, while contextually innovative, was based on history – it echoed the revolutionary principles laid down by one of the great scientists of the 19th century, Louis Pasteur. Pasteur, known for his remarkable work in microbiology and chemistry, fundamentally transformed our understanding of food safety through the process of pasteurization.

Pasteurization, named after Louis Pasteur, involves heating food products to a specific temperature for a set period to eliminate most pathogenic microorganisms. This technique was a monumental step forward in ensuring the safety of foods, particularly milk and wine, without compromising their nutritional and health benefits. Pasteur's method not only extended the shelf life of perishable items but also preserved many of their inherent nutritional qualities, paving the way for a new era in food processing and preservation. 

At Thaena®, our approach to microbiome therapy is deeply influenced by the ethos of Louis Pasteur. Embracing his foundational principle of pasteurization, which involves applying heat to eliminate harmful elements while preserving beneficial properties, we adapted this concept to stool. Our method, however, introduces a novel twist: We utilize autoclaving, a more intense form of heat sterilization than traditional pasteurization, to enhance the safety of our microbiome product, ThaenaBiotic®. Our process involves a proprietary method of sterilizing healthy donor stool to kill bacteria and viruses, yet crucially retains the vital postbiotic metabolite molecules that  have been studied and shown to support human health. Our innovative approach not only ensures the safety of our end product but also maintains the therapeutic potency of these postbiotic molecules.

In this venture, we draw parallels to Pasteur's revolutionary contributions to food safety, stepping into a new era where a flood of new research is looking at pasteurized probiotics and postbiotics shedding light on the physiological roles of the microbiome. By reimagining and repurposing established scientific principles, we have embarked on a journey to explore the untapped potential within our microbiome. A golden opportunity in a turd - if you will. As Pasteur transformed food safety, our exploration and work by other scientists into pasteurized microbial products is pioneering a new frontier in microbiome therapy. This exciting convergence of historical wisdom and modern innovation is allowing us to hypothesize about what is happening with ThaenaBiotic®, and where the future may lie in product development. Below is just a sampling of some of the fascinating work that has been done looking at the health implications of heat-killed bacteria and postbiotics, that we are keeping an eye on as we think about ThaenaBiotic®. 

Heat-Killed Probiotics and Postbiotics: Recent Studies Challenging the Live Microbe Paradigm

The recent surge in research around heat-killed probiotics and postbiotics represents a fascinating turn in the story of microbiome therapy. In 2023 alone, significant strides have been made in understanding how these molecules, derived from and retained in heat-killed bacteria preparations, can influence human health. This section delves into some key studies that highlight the health benefits and mechanisms of these heat-killed probiotics and postbiotics.

Human Studies 

• Similarly, Shinkai et al. (2013) explored the effects of heat-killed Lactobacillus plantarum L-137 on inflammation and lipid metabolism in overweight adults. The findings suggested that daily intake of heat-killed L-137 can improve inflammation and lipid metabolism in individuals at risk of inflammation. This study aligns with the growing body of evidence that heat-killed probiotics can positively impact metabolic health.
• One landmark study by Tanaka et al. (2020) focused on the immunoprotective effects of the oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults. This randomized, double-blind, placebo-controlled trial showed a significant reduction in the incidence rate of the common cold among elderly adults who consumed heat-killed b240. Not only did this study confirm the ability of heat-killed bacteria to modulate the immune system to protect against infection, but it also underscored the role of mucosal immunity in enhancing resistance against common pathogens.
• Lee et al. (2022) conducted a comparative analysis of viable and heat-killed Lactiplantibacillus plantarum TWK10 on exercise performance and gut microbiota in healthy adults. The results revealed that both viable and heat-killed TWK10 improved exercise performance, reduced exercise-induced inflammation, and had distinct impacts on shaping gut microbiota. This study highlights the potential of heat-killed probiotics in sports nutrition and exercise-related health benefits.
• Furthering this narrative, Cheng et al. (2023) demonstrated that heat-killed Lactiplantibacillus plantarum TWK10 significantly improved exercise endurance, muscle strength, and reduced fatigue in healthy male adults. These findings underscore the versatility of heat-killed probiotics in promoting physical health and enhancing athletic performance.
• Sato et al. (2023) investigated the effects of heat-killed Lacticaseibacillus paracasei MCC1849 on physical condition maintenance in healthy adults. The study showed a reduction in the duration and incidence of cold-like symptoms, emphasizing the potential role of heat-killed probiotics in maintaining overall physical health and wellness.

Pre-clinical Studies

• Hu et al. (2023) explored the effects of Lactiplantibacillus plantarum postbiotics on Salmonella infection in mice. The study found that heat-killed bacteria and metabolites had similar or superior effects compared to live probiotics against Salmonella, providing insights into the role of postbiotics in animal health and potentially in human health as well.
• Zhu et al. (2023) highlights the potential of Lactobacillus plantarum Zhang-LL in combating colorectal cancer. This research utilized both live and heat-killed strains of L. plantarum Zhang-LL, demonstrating their significant impact in reducing tumor growth and inflammation in mice. 
• The work of Magryś et al. (2023) sheds light on the potent effects of postbiotic fractions from Lactobacillus plantarum and Lactobacillus rhamnosus on inflammation control and immune response in cell culture. Their discovery that heat-killed fractions and proteins from these probiotics effectively protect intestinal barrier integrity offers exciting prospects. 
• A fascinating study by Balaguer et al. (2023) has revealed the significant role of Bifidobacterium animalis subsp. lactis BPL1™ in improving lifespan and stress responses. This research, focusing on the nematode Caenorhabditis elegans which parallels work done with Thaena®Biotic in the same model system.
• The research conducted by Malek et al. (2023) brings to light the impact of Bacteroides fragilis on the endocannabinoid system and gut epithelial integrity in cell culture. Their findings on how both live and heat-inactivated forms of B. fragilis affect genes related to gut health underline the possible mechanisms beyond the gut locally. 
• The study by Spragge et al. (2023) emphasizes the critical role of a diverse gut microbiome in providing defense against pathogens in bacterial culture. Through nutrient blocking, a varied bacterial community can significantly reduce the growth of harmful pathogens such as Klebsiella pneumoniae and Salmonella typhimurium. 

These studies collectively paint a promising picture for the potential of single strain heat-killed probiotics and postbiotics along with the importance of the synergistic effects of microbe postbiotics in mixtures. Imagine what we will uncover as we begin to study the mechanism of action of more complex mixtures of heat-killed bacteria like those found in stool?! 

While research on autoclaved bacteria is still emerging, the parallels drawn from pasteurization and these recent studies lay the groundwork for exploring the full potential of stool derived heat-killed products in various aspects of health. We are thrilled about the response that ThaenaBiotic® has been getting anecdotally in supporting its consumers. Our hope is that this work and our own preclinical research will all come together to significantly shift the live bacteria needed narrative and paradigm. 

Conclusion

In the realm of microbiome therapy, Thaena® stands at the forefront of a pioneering journey, blending the wisdom of ancient myths with the rigor of modern science. Our venture, inspired by the mythical Thanatos and guided by the revolutionary principles of pasteurization, is more than a scientific endeavor—it's a fantastical adventure into the unknown realms of health and healing. As we dive deeper into the transformative potential of heat-killed probiotics and postbiotics, we are not just revisiting the past but aiming to redefine the future of healthcare.

Our story, rooted in the practice of Fecal Microbiota Transplantation, has evolved into the innovative development of our postbiotic dietary supplement, ThaenaBiotic®. This product represents the culmination of years of dedication, research, and a bold willingness to challenge conventional paradigms. By embracing the complexity of the microbiome and harnessing the power of postbiotics, we are navigating uncharted territories in microbiome-based products. The groundbreaking studies in heat-killed probiotics and postbiotics are not just validating our crazy idea, but are also opening new horizons in understanding human health. 

Thanks for coming along for the ride. We cannot wait to see what lies ahead!

References

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