A growing body of research links the gut with the brain and behavior, but compartmentalization within the medical community may be slowing investigation of the gut-brain axis, according to a leading expert.
Studies have shown that the microbiome may influence a diverse range of behavioral and neurological processes, from acute and chronic stress responses to development of Parkinson’s and Alzheimer’s disease, reported John F. Cryan, PhD, of University College Cork, Ireland.
Dr. Cryan began his presentation at the annual Gut Microbiota for Health World Summit by citing Hippocrates, who is thought to have stated that all diseases begin in the gut.
“That can be quite strange when I talk to my neurology or psychiatry colleagues,” Dr. Cryan said. “They sometimes look at me like I have two heads. Because in medicine we compartmentalize, and if you are studying neurology or psychiatry or [you are] in clinical practice, you are focusing on everything from the neck upwards.”
For more than a decade, Dr. Cryan and colleagues have been investigating the gut-brain axis, predominantly in mouse models, but also across animal species and in humans.
At the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, Dr. Cryan reviewed a variety of representative studies.
For instance, in both mice and humans, research has shown that C-section, which is associated with poorer microbiome diversity than vaginal delivery, has also been linked with social deficits and elevated stress responses. And in the case of mice, coprophagia, in which cesarean-delivered mice eat the feces of vaginally born mice, has been shown to ameliorate these psychiatric effects.
Dr. Cryan likened this process to an “artificial fecal transplant.”
“You know, co-housing and eating each other’s poo is not the translational approach that we were advocating by any means,” Dr. Cryan said. “But at least it tells us – in a proof-of-concept way – that if we change the microbiome, then we can reverse what’s going on.”
While the mechanisms behind the gut-brain axis remain incompletely understood, Dr. Cryan noted that the vagus nerve, which travels from the gut to the brain, plays a central role, and that transecting this nerve in mice stops the microbiome from affecting the brain.
“What happens in vagus doesn’t just stay in vagus, but will actually affect our emotions in different ways,” Dr. Cryan said.
He emphasized that communication travels both ways along the gut-brain axis, and went on to describe how this phenomenon has been demonstrated across a wide array of animals.
“From insects all the way through to primates, if you start to interfere with social behavior, you change the microbiome,” Dr. Cryan said. “But the opposite is also true; if you start to change the microbiome you can start to have widespread effects on social behavior.”
In humans, manipulating the microbiome could open up new psychiatric frontiers, Dr. Cryan said.
“[In the past 30 years], there really have been no real advances in how we manage mental health,” he said. “That’s very sobering when we are having such a mental health problem across all ages right now. And so perhaps it’s time for what we’ve coined the ‘psychobiotic revolution’ – time for a new way of thinking about mental health.”
According to Dr. Cryan, psychobiotics are interventions that target the microbiome for mental health purposes, including fermented foods, probiotics, prebiotics, synbiotics, parabiotics, and postbiotics.
Among these, probiotics have been a focal point of interventional research. Although results have been mixed, Dr. Cryan suggested that negative probiotic studies are more likely due to bacterial strain than a failure of the concept as a whole.
“Most strains of bacteria will do absolutely nothing,” Dr. Cryan said. “Strain is really important.”
In demonstration of this concept, he recounted a 2017 study conducted at University College Cork in which 22 healthy volunteers were given Bifidobacterium longum 1714, and then subjected to a social stress test. The results, published in Translational Psychiatry, showed that the probiotic, compared with placebo, was associated with attenuated stress responses, reduced daily stress, and enhanced visuospatial memory.
In contrast, a similar study by Dr. Cryan and colleagues, which tested Lactobacillus rhamnosus (JB-1), fell short.
“You [could not have gotten] more negative data into one paper if you tried,” Dr. Cryan said, referring to the study. “It did absolutely nothing.”
To find out which psychobiotics may have an impact, and how, Dr. Cryan called for more research.
“It’s still early days,” he said. “We probably have more meta-analyses and systematic reviews of the field than we have primary research papers.
Dr. Cryan concluded his presentation on an optimistic note.
“Neurology is waking up ... to understand that the microbiome could be playing a key role in many, many other disorders. ... Overall, what we’re beginning to see is that our state of gut markedly affects our state of mind.”
Dr. Cryan disclosed relationships with Abbott Nutrition, Roche Pharma, Nutricia, and others.