The Search for Mood Microbes

In May, the American Psychiatric Association confirmed what many Americans have been feeling individually: Anxiety is rising sharply. 

What if humble bacteria held the solution? The early science on probiotics focused on the part of the body with the greatest biodiversity: the gut. Digestion and metabolism offered obvious targets, and discoveries in that area produced a whole new category of wellness products, including the probiotic known as B420™, a weight-management breakthrough. More recently, scientists have noticed something new and surprising, the microbes in your gut affect what happens in your brain. 

Now, DuPont scientists are combing through data from a recently completed clinical trial to figure out how probiotics could help address one of the most widespread and corrosive characteristics of modern life: stress.

The potential human and social benefit is massive, as is the potential market. Millennials, now America’s largest generation, suffer from anxiety at higher rates than any previous generation, and millions of people who suffer from mild anxiety or mild depressive symptoms might prefer a probiotic to pharmaceutical treatments. 

As a result, DuPont researchers are looking in the belly for potential solutions for the brain. 

A new scientist for a new science 

Until recently, microbiologists studying gut bacteria had little reason to think about brain physiology, behavior, and signaling, and neuroscientists focused solely on the brain—the gut microbiome wasn’t on their radar. But with growing interest in the gut-brain frontier, DuPont needed a new kind of scientist to lead this ground-breaking exploration. “We’re wading into new waters, so new, unique microbiological competencies need to be brought in,” says Martin Kullen, Global Research And Development Lead for microbiome, probiotics, HMOs, dietary fibers, and animal nutrition at DuPont.

Enter Elaine Patterson, who studied neuroscience as an undergraduate at University College Cork in Ireland, before earning a doctorate in microbiology. She worked extensively on probiotic interventions at a time when most of the research dealt with digestion and metabolism. Toward the end of her post-doctorate studies, though, Patterson discovered the relatively new field of the microbiome-gut-brain axis. An increasing volume of literature was emerging, linking the gut microbiome and the molecules it produces with brain signaling and behavior, and it was becoming clear that differences existed between the gut microbes in patients suffering from mental disorders such as depression and those in healthy individuals. Patterson was hooked. 

When DuPont came calling in 2017, she jumped at the chance to lead this new initiative. She’s now a senior scientist at its Health & Nutrition Sciences Lab in Kantvik, Finland.

“I am truly passionate about this research topic,” Patterson says. “It connects my two research backgrounds: neuroscience and microbiology. There’s a lot of attention on how probiotic intervention, or indeed the gut microbiome itself, can influence brain physiology, function, and even behavior.”

In other words, she’s the perfect brainiac for the next frontier in probiotics. 

Gut-checking anxiety

Initially, gut-brain research focused on behavior in animal studies. It became clear from the use of germ-free rodents (i.e., those born and raised in the absence of any gut microbes) that they had alterations in neural function, behavior patterns, neuroprotection, and altered stress hormone signaling. Early preclinical probiotic intervention studies demonstrated that supplementing the rodent diet with live microbes could influence behavior.

But translating these discoveries to clinical research wasn’t easy. A lot of the early clinical research didn’t explore stress-related disorders such as anxiety. Today, says Patterson, scientists are seeing the tip of the iceberg with discoveries following probiotic supplementation in patients experiencing exacerbated symptoms of stress and whole-body symptoms of anxiety. They’re also expanding research into neuropsychiatric, developmental, and degenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, autism, and clinical depression, which has attracted collaborations between neuroscientists and microbiologists.

Recently, however, DuPont and others have begun addressing health issues that affect large segments of the population but don’t typically rise to a level of severity that requires medical intervention—which is why these issues haven’t been top of mind for neurobiologists. Encouraged by enthusiasm from hopeful consumers and partners eager to tap new markets, they’ve started to gauge the microbiome’s effects on everyday conditions, such as stress, anxiety, and mental fatigue.

Patterson and the team working on cognitive health are putting in long hours to lay the groundwork for these disorders’ future probiotic treatments. It’s an example of innovation in the making with potentially life-changing societal impact. 

Uncovering the story of a microbe

Discovering effective non-pharmaceutical remedies requires pharma-quality rigor. It’s one thing to observe that gut microbes affect brain activity. It’s another to figure out which microbes affect the brain, how that interaction works, and the specific effects exerted by a given strain of bacteria.

DuPont takes a clinical research-heavy approach to locate and develop the most effective probiotic candidates. Scientists start by sifting through numerous potential probiotic strains, each bearing unique properties and producing distinct results. The researchers weed out unlikely strains to hone in on the most promising candidates, eliminate those that are unsuitable in terms of safety, stability, or manufacturing performance, and then work with the remaining strains to find ones that can survive the journey through the human digestive system long enough to be effective and deliver a health benefit.

“You can have hundreds, even thousands, of strains in biobanks to screen from,” Patterson says, “and even if they’re strong candidates, they then need to produce a health benefit for brain behavior and function.”

That’s where the hardest work begins. After DuPont’s scientists find a strain that checks all of the necessary boxes, they begin an entirely new research cycle to find out exactly why it acts as it does. Many probiotic effects are subtle: Experimental results can be hard to reproduce, and the mechanism by which a microbe influences brain activity can be elusive.

“We can’t just say that a bacterial strain is influencing a brain function or behavior. We have to understand why,” Patterson says. “Before we create a probiotic product, we must be able to piece together the story of how and why it works—the whole story, complete from start to finish.”

That detective work can be painstaking, in part because even similar microbes can have very different stories. For instance, many lactic acid bacteria and strains of Lactobacillus can produce specific neurotransmitters. “But how much they produce is very different between strains, as are the ways they influence the brain,” Patterson says. So today, the team is working methodically to create profiles of each potential mood microbe—and each new story brings DuPont closer to creating effective, beneficial products. 

The tip of the iceberg

As Patterson and the team pore over the data from their clinical trial on stress and anxiety, they have two other ongoing trials looking at mental fatigue and cognitive function in the elderly. What scientists learn from these trials will not only shape the future of probiotic therapies in these areas, but will also form the basis for a deeper understanding of the microbiome-gut-brain axis.

Future research may extend novel therapies into clinical areas such as dementia, Alzheimer’s, and Parkinson’s, potentially uncovering connections beyond any current scientist’s wildest dreams. Clinicians and consumers alike are keeping an eye on these developments, eager for a glimpse of the next brain innovation. It could very well be growing quietly in DuPont’s lab in Kantvik, Finland, right now—a new microbe story just waiting to be found.