Timothy Brown

CEO, Evolve BioSystems

Talking about the health of our gut microbiome is nothing new, though we generally think of it as an adult concern. New research is showing that nine out of ten babies have Newborn Gut Deficiency—which means pathogenic bacteria has overwhelmed their digestive tract. In fact, the dominant good bacteria in the infant gut, B. infantis, is disappearing most likely caused by the upswing in cesarean births, the prevalence of antibiotics, and the favoring of formula over breast milk. Common maladies such as diaper rash, eczema, and colic can actually be signs that your baby’s gut is out of balance. Enter Evivo, a product created by Evolve BioSystems and the only clinically proven baby probiotic or “evolutionary symbiont,” as they prefer to call it. Evivo’s activated B. infantis EVC001 can provide almost instant relief by turning on the genes needed for babies to absorb the key nutrients in their mother’s breast milk. Without restoring the critical good bacteria, long-term health concerns such as asthma and even Type 1 Diabetes can develop. The results are so astounding, the Bill and Melinda Gates Foundation, Cargill, and Manna Tree Partners are amongst the investors.

How did Evolve BioSystems come about?
Evolve BioSystems spun out of the Foods for Health Institute at UC Davis where our five faculty founders were alarmed by the pandemic of autoimmune and allergic conditions (eczema, asthma, food allergies) afflicting our children. Working from the knowledge that the bacteria in the large intestine or “gut” play an important role in the development of the immune system, as well as the fact that the bacterial composition of the gut is driven by the diet, they began studying the relationship between breastmilk and the infant gut microbiome. Unlike adults, infants have a sole source of nutrition for the first months of life, and thus only one type of “prebiotic” or gut-feeding fiber. What they found was that the third most abundant component of breastmilk, human milk oligosaccharides (HMOs), is that bacteria-feeding prebiotic and that HMOs can only be made useful to the baby by a unique bacterium called B. infantis.  Further research has shown the critical role that B. infantis plays in transforming breastmilk nutrients to compounds that shape immune system development. Unfortunately, B. infantis has been nearly wiped out in the United States and other developed nations. Evolve BioSystems is now on a mission to restore B. infantis to all babies globally and reestablish the important function it provides to babies’ developing immune systems.

The digestive tracts of babies are radically changing due to cesarean births, antibiotics, and formula. Can you discuss specifically how these are affecting babies’ guts? For instance, how would a cesarean birth impact a baby’s digestive tract?
The anatomy of our babies’ digestive tracts has not changed a bit. However, what has radically changed over the past fifty years is the gut’s bacterial composition and function. Like all humans, infants have trillions of bacteria in their large intestine which interact with each other, creating very complex biochemistry. Thus, these bacteria drive many aspects of infant health, including the development of the immune system.

Childbirth is inherently messy, and throughout evolution, as a woman was giving birth, the bacteria in her gut would pass directly into the baby’s mouth effectively “seeding” the microbiome in the last stages of delivery.  These gut bacteria (not vaginal bacteria, which are different), would pass through the baby’s digestive tract to take hold in the gut and then replicate quickly to establish the baby’s initial gut microbiome. However, when a baby is delivered by C-section, it is not exposed to the mother’s gut bacteria. Instead, the baby acquires bacteria common in a hospital environment, including antibiotic resistant E. coli, which take hold and grow in the infant gut. We believe the biggest culprit in the change of the gut microbiome of American infants is the mothers’ exposure to antibiotics throughout her lifetime.  These antibiotics have likely killed off any B. infantis she may have been carrying in her gut, long before her pregnancy. At present, the vast majority of American women simply don’t have B. infantis to pass on to baby. This lack of B. infantis in the baby gut leads to a condition which is now being called Newborn Gut Deficiency (NGD), the absence of good, pathogen-suppressing bacteria and the special biochemistry they produce to help the immune system develop properly.

Evolve conducted a study with the International Centre for the Study of Diarrheal Diseases, Bangladesh (or icddr,b) on the effect of Evivo in treating infants with Severe Acute Malnutrition that was sponsored by the Gates Foundation.

How does your product, Evivo, help to resolve Newborn Gut Deficiency?
Although it takes place in the digestive tract, we should think about Newborn Gut Deficiency (NGD) as an issue for nutrition and immune system development. NGD occurs when pathogenic bacteria are allowed to thrive in the gut and cause inflammation which disrupts the programming of the immune system. Most recently, we showed that NGD is a likely key driver of the pandemic of autoimmune and allergic conditions like food allergies, eczema, asthma and Crohn’s Disease from which our children now suffer. Evivo contains an activated form of a specific strain of B. infantis–EVC001–which is clinically proven to colonize the infant microbiome and alter the gut biochemistry in a beneficial way. Through a series of clinical studies, we have shown that EVC001 consumes the HMOs in breastmilk and turns them into nutrients which perform two major roles. First, these nutrients are now available for the baby to use.  Lactate and acetate, for example, provide nourishment to developing neural cells. Second, these nutrients help train the immune system in a healthy way, as well as suppress the growth of pathogens in the gut which cause inflammation and inhibit proper immune development. No other product has been shown to address NGD.

Are environmental changes such as depleted soil and polluted water and air also having an impact?
As far as we can tell, the unintended consequences of important, modern medical practices like antibiotics and C-section delivery have played the biggest role in the loss of B. infantis among our young women and then, as a result, their offspring.

Why isn’t mother’s breast milk able to supply the crucial B. infantis?
There is a common misconception that breastmilk contains B. infantis. This is not the case. B. infantis requires the specific, anaerobic (oxygen-free) environment of the large intestine to thrive and is only found there. After B. infantis is seeded during the birthing process, Evivo is “fed” by the HMOs in breastmilk and thrives to become the dominant species of bacteria in the gut. Once again, it is important to remember that the critical issue is that young women don’t have this species of bacteria to pass on to their babies, regardless of how they deliver their babies and how or what they feed them.

Is this a Western phenomenon or is it happening worldwide? If it is largely Western, why?
It appears to be an issue wherever C-section delivery and antibiotics have been in widespread use for a couple of generations. Very recently, a researcher from the University of Rochester published a study showing that the infants in the Old Order Mennonite community in the Finger Lakes Region of New York tend to have high levels of B. infantis, so there may be small pockets of it remaining in the United States. However, when we look at healthy infant populations in the developing world, the vast majority of infants have very high levels of B. infantis in their gut. The future danger in these areas is that poorly controlled use of antibiotics may reduce B. infantis prevalence in the community and lead to the same result we have today in the U.S. and Europe. Hopefully, we can intervene in time to prevent this from becoming a problem there also.

Will a baby need to stay on a probiotic into childhood and possibly adulthood?
We know that breastmilk provides everything a baby needs to grow until they are about six months old.  This suggests that through human evolution, the infant gut microbiome would have been dominated by B. infantis for the first six months. Growing evidence, including the peer-reviewed paper we published recently in the journal Cell, suggests that the window of the first 100 days is critically important for immune system development. As the baby gets older and the diet diversifies away from breastmilk, the dominance of B. infantis will subside and a wider range of the right bacteria grow in relative abundance.   Ultimately EVC001 creates the right environment for health-promoting bacteria (commensals) in the gut to grow upon food introduction.

What kind of results are you seeing?
The clinical results of Evivo have been consistently outstanding and each study sheds more light on the important role B. infantis plays in infant health. At the simplest level, we have confirmed that feeding Evivo to infants leads to a substantial increase in good gut bacteria, a reduction in the abundance of pathogens by as much as 80%, and an increase in the nutrients important to the baby’s immune development. Our data also shows that infants’ stooling patterns improve significantly, with fewer loose and watery stools. As shown in our peer-reviewed paper, more than 1,600 parents told us that Evivo reduced fussiness, gassiness, and diaper rash, and it improved sleep—and that these improvements were seen relatively quickly even after the first feeding. There are some very large, long-term studies underway right now to see if Evivo prevents Atopic Dermatitis (eczema) and Type 1 Diabetes (also known as Juvenile Diabetes). If these studies are successful, we will be very confident of reductions in the prevalence of food allergies and asthma because these conditions all have similar underlying causes.

How do parents and caregivers determine if their baby is missing B. infantis?
Our data suggests that more than 90% of American infants do not acquire B. infantis during the crucial first few months of life. Colic, which is caused by inflammation, is a very common sign of Newborn Gut Deficiency. Diaper rash is also a very strong signal, as it shows that the infant’s gut is not acidic enough to suppress pathogens. So, in some ways, we can recharacterize the typical “rites of passage” symptoms of fussy baby as signs of Newborn Gut Deficiency. LabCorp of America, one of the world’s leading diagnostic laboratories, offers a pH test of a baby’s stool. Infants with a stool pH above 5.5 are considered out of the reference range and thus very likely to have Newborn Gut Deficiency.

Before joining Evolve, you worked in global healthcare, consumer goods, and pediatric nutrition industries. What experience did you bring from that into your current work?
I originally chose the healthcare and nutrition field in order to help others, so when I learned about Evolve’s science and mission, I knew immediately that I needed to be in service to help restore B. infantis and reestablish what we have lost from nature. My years of working on pediatric nutrition taught me that what Evolve was tackling would offer the biggest impact of my career by far. With each baby fed Evivo, we are changing the trajectory of that baby’s health for life and improving bonding and quality of life for the mother. Collectively, we aim to transform public health on a national scale. Evolve represents a full integration of all my experiences—each tested when I had to adapt them to a start-up setting. I have focused on hiring talented and like-minded people who realize that this is more than a business, it is a mission.

In addition to Evivo, is there anything parents and caregivers can do to improve the vibrancy of their baby’s digestive tract?
Nature spent millions of years perfecting a symbiotic relationship between breastmilk and B. infantis to create the right environment in the gut for the baby’s immune system to develop properly. It is very important to do this in the first hundred days of life. We also think that it is important for mothers to proactively build a healthy gut microbiome from preconception through and especially late in pregnancy, and to breastfeed as long as possible.

What’s the difference between Evivo and other infant probiotics on the market?
Evivo differs from other products on clinically proven function, specificity of strain, and care of manufacture and handling. We prefer to refer to Evivo as an evolutionary symbiont, not a probiotic. The difference is that “probiotic” is a very general term that covers hundreds of different species coming from various sources and which may or may not perform specific health benefit function. We know that the bacteria in Evivo co-evolved with humans over millennia feeding on a single nutritional source, HMOs, in order to create special biochemistry for a cascade of critical functions for the infant. No other bacterium plays this role, and babies face a suboptimal health outlook without it. Not only have we done the clinical work to show that Evivo performs these important functions, we have also published findings that show other strains of B. infantis do not. The bacterium is a complex organism containing roughly 2,500 genes, and each strain may differ from the next by dozens of genes. In a peer reviewed paper, we showed that because of genetic differences, the strain in Evivo is superior to other B. infantis strains in its ability to break down HMOs. Finally, and unlike our competitors, we take special care through refrigerated handling to ensure that the bacteria in each package of Evivo remains viable and ready to perform its important role right to the consumer’s home.