Speed Round: David Kyle on The Microbiome as a Disruptor

Welcome to The Microbiome Coalition's Speed Round series in which we ask key opinion leaders a single question about the latest happenings in the microbiome sphere. We hope you enjoy!

In this Speed Round, we feature David Kyle, Chief Scientific Officer at Evolve BioSystems.  

TMBC: What’s the potential for microbiome-based interventions to disrupt the conventional industry approach, both in terms of operating outside the intensely expensive and restrictive therapeutic model and in being able to help more people? 

Kyle: First, most of the major microbiome companies are already operating inside the restrictive therapeutic model as they are working on clinical interventions with clinical outcomes. They are developing microbiome-based drug strategies in that their products are treating, curing, mitigating or preventing a disease. Their challenge is to identify the dysbiosis associated with a clinical condition and how to revert it to a healthy state, when the healthy state is only defined by lack of clinical symptoms. Although they are operating in a therapeutic model, it is difficult to follow the well-established path of typical pharmaceutical products that has been developed over the past 50 years. Without a clear target of what is healthy, such as blood cholesterol goals, or blood sugar levels, we must restructure the therapeutic model to apply it to microbiomal remodeling.

Conversely, in the unique case of the infant microbiome we have a clear definition of a healthy microbiome as it has been defined by over 5 million years of evolution. It is unique because the first six months of life is the only time in our human life history that we have a single-source of nutrition. This also means a single-source of nutrition for our microbiome.  Until recently the oligosaccharide component of human milk (HMO) was an enigma as it represents about 15% of milk’s energy content and it is totally unusable by the human infant. Discoveries at the University of California at Davis established that this was the food for the microbiome and, unexpectedly, only a single bacterial species (Bifidobacteria longum subspecies infantis) was found to totally deconstruct the HMOs and convert them into usable nutrients (e.g. acetate, lactate, and other important metabolites) that are fed back to the baby. 

Unfortunately, over the past 60 years we have been unknowing participants in a worldwide microbiome remodeling experiment that has left us on the verge of extinction of this keystone commensal. Through the multigenerational use of antibiotics [1], alternatives to breast milk [2] and, more recently, delivery by C-section and our obsession with hygiene [3], we have found that this organism has disappeared from nearly all populations that have been heavily impacted by these modern medical practices. The infant microbiome that was once dominated by bifidobacteria (most likely B. infantis) is now rich in proteobacteria, enterobacteria, and clostridia, and it is possible, but certainly not yet proven, that this could be the cause of the expanding worldwide pandemic of autoimmune disorders, metabolic disorders, and perhaps neurological disorders that appear later in life.

Evolve has recognized this change in the infant gut microbiome and demonstrated that by resupplying this keystone commensal to the breast-fed human infant, the original microbiome can be restored. This takes us out of the therapeutic model – intended to treat or mitigate - as it simply is a restoration of the natural microbiome that has partnered with human milk for millions of years to provide the best nutrition for the baby. Indeed, this meets a specific dietary need that is unique to the infant by simply putting back what was unintentionally lost over the past 60 years as the unintended consequences of modern medical practices. Since the B. infantis consumes the HMOs and gives back other important nutrients (e.g., lactate and acetate) for the baby to use, we are really talking about food and nutrition. In this case, dysbiosis is defined as a microbiome that is unable to utilize the HMOs in breast milk resulting in a loss of those HMOs in the stool, and the healthy microbiome as one that restructures this HMO energy source into important nutritional components that can be used by the baby and not lost in the stool.

When you ask about the potential of this approach, we must realize that this dysbiosis is affecting the majority of new babies born in the developed world today. Consequently, we are talking about tens of millions of babies that need this microbiomal “unremodeling.” If we followed a traditional drug process and approach, the solution would not be available to parents for another 5-10 years, which clearly does not help those who are having babies today. We at Evolve believe we have a moral and ethical imperative to bring this choice to parents as soon as possible. That is why we have launched Evivo - to give parents the choice of either providing their new baby with the original natural microbiome, or simply defaulting to the new “normal” of the dysbiotic microbiome during the first few critical months of life when the immune system is just developing.

[1] B. infantis is particularly sensitive to antibiotics

[2] IMFs do not provide the HMOs required for B. infantis to survive

[3] Preventing the historical fecal/oral transfer of mom’s microbiome to her baby