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What’s Your Psychobiome Telling You?

“Warren Buffet told me once and he said always follow your gut. When you have that gut feeling, you have to go with don’t go back on it.”

- LeBron James “What a weird concept—that the bugs we lug around appear to be essential to establishing the basic nature of who we are.” - Robin Marantz Henig, American science writer


A little over a year ago in a Germ Gem post “Does Your Microbiome Shape Happiness?,” I wrote: “Today is January 1, 2020—the start of a new, and hopefully, happy year.” For all of us 2020 was anything but a happy year. Instead, we are living through a global pandemic caused by SARS-COV-2, the virus that by the end of the year claimed the lives of 1.8 million people worldwide and changed the way we all live. Since late February 2020 when this nasty virus caused all of us to sit up and take notice, most of my Germ Gem posts have addressed the COVID-19 pandemic. This week I decided to deviate a bit and revisit the human microbiome, this time focusing on the component referred to as the psychobiome—the microbes in your gut that affect how you think and act. But for those whose interest in science has been subsumed by SARS-COV-2, read on! It appears that there may be a connection between the gut microbiome and COVID-19.


The Human Microbiome Revisited. You may recall from last year’s January 1 Germ Gem post that about twenty years ago the Nobel laureate Joshua Lederberg defined the human microbiome as “an ecological system of commensal, symbiotic, and perhaps pathogenic microorganisms that reside in the human body.” Simply put, the human microbiome refers to the microbes (bacteria, archaea, fungi, viruses, and protists) that share our body surfaces. Spurred by the National Institutes of Health (NIH)-funded “Human Microbiome Project” initiated in 2008, researchers from a variety of fields took up in earnest the challenge of characterizing the composition of the microbes living in five of our body’s ecosystems: the gut, vagina, mouth, and respiratory tract and on our skin.


The goal of the Human Microbiome Project is to discover associations between the microbes residing in each of these ecosystems and human health and diseases. While great progress toward this goal has been achieved in the past dozen years, most of the attention has been on the gut microbiome, where most of our germs reside. (The creativity and talent of the basic science and clinical researchers working on the gut microbiome continues to amaze me. Just imagine trying to find clinically meaningful associations between the roughly 40 trillion bacteria residing in the gastrointestinal tract and health and diseases. On top of that consider that there are about 380 trillion viruses in the gut that still need to be accounted for.)

Blame it on your gut microbiome. Like all areas of human microbiome science, the field of psychobiome research is in its infancy. Analogously, recent studies using mouse models showed that a mouse mother’s microbiome shapes the wiring of her offspring’s brain and behavior. In a January 2020 National Geographic article, “How trillions of microbes affect every stage of your life—from birth to old age,” Robin Marantz Henig refers to a study by Anna-Katarina Aatsinki and her colleagues at the University of Turku in Finland, which showed the microbiome of an infant’s gut can affect something as innate as the child’s temperament—the more Bifidobacterium bacteria, the sunnier the baby’s disposition. And a new study from Oxford University, published in the journal Human Microbiome, linked gut bacteria strains and diversity to people’s personalities, including sociability and neuroticism.


These studies are raising new questions about what’s referred to as “gut instinct” or intuition, defined as your immediate understanding of something with no need to think it over or get another opinion—that is, you just know. In the field of neuroscience it has been known for decades that the emotional or subcortical (non-thinking) part of the brain influences and often overrides decisions and behaviors generated by the cortical (thinking) part of the brain. But is it also possible that the gut microbiome has a say in the operation of your emotional brain. As just one example, could the person you fall in love with be influenced by your psychobiome?


How does it work? Several mechanisms are proposed on how the microbes in your gut could influence your brain. First, some microbes secrete messenger molecules that may travel through the blood to the brain. (Gut bacteria both produce and respond to the same neurochemicals—such as serotonin, norepinephrine, dopamine, acetylcholine and melatonin—that the brain uses to regulate mood and cognition.) Second, bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Neurotransmitters produced by bacteria in the gut might relay signals to the vagus nerve that in turn stimulates the brain. Third, indirect links may also exist via microbial stimulation of cells of the immune system that in turn release molecules that affect the brain.


In the past decade, researchers John Cryan and Ted Dinan at University College Cork in Ireland have pioneered studies on the association between the gut microbiome and depression and anxiety. They have shown, for example, that fecal samples from patients with major depressive disorder have differences in 47 bacterial species when compared with samples from healthy controls. Along with collaborators in China, these researchers recently reported that the bacterium Bifidobacterium breve showed considerable antidepressant-like effects, supporting their ultimate goal to find novel “psychobiotics” to treat depression. (Intriguingly, other researchers have noted an increase in depression in people who are taking antibiotics, which eliminate gut bacteria; whereas, a similar increase was not found in people receiving antiviral or antifungal drugs that have no effect on gut bacteria.

Another area of neuroscience research where the gut microbiome is receiving increased attention is sleep. In a November 30, 2020 article in Science News entitled “Gut microbes: A key to normal sleep,” researchers from the University of Tsukuba in Japan reported that mice treated with antibiotics to deplete their gut microbiome had markedly disrupted sleep. They speculated that a lack of serotonin (one of the neurotransmitters produced by bacteria that is known to affect sleep/wake cycles) in the gut of antibiotic-treated mice plays a key role in their sleep abnormalities. At the same time, University of Missouri researchers are investigating the role of the gut microbiome in obstructive sleep apnea, a disorder that affects more than one billion people worldwide.


In addition to an interest in the role of the psychobiome in psychiatric disorders, such as, depression and anxiety, researchers are also exploring the influence of the microbiome in eating disorders such as obesity. For example, one question they are asking is whether overeating could be due in part to microbes signaling the brain to take in more food for their own benefit. In addition, researchers are exploring the connection between the microbiome and autism and cognitive abnormalities, like Alzheimer’s disease.


Gut microbiome and COVID-19 connections. Since its inception in December 2019, a day has hardly gone by without something new being reported about COVID-19. For example, we’ve learned that gastrointestinal symptoms are relatively common in patients with COVID-19. So it’s not surprising that there is a rapidly growing interest in potential meaningful links between the gut microbiota and the clinical outcomes of infection, ranging from asymptomatic infection in over 50% of infected people to fatal disease in less than 1%.


Beginning at the time of birth, our gut microbiome rapidly becomes established but its composition changes over time. It is now known that one of the sustaining functions of the gut microbiome is to “educate” cells of the immune system by shaping how they respond to foreign substances, like allergens and microbes. It is also known that as we age the composition of our gut microbiome becomes depleted, that is, the diversity of the bacterial species harbored in the gut declines.


Based on this knowledge, several research groups are trying to find out whether the difference in severity of COVID-19 infection is due, in part, to the composition of the gut microbiome. It is hypothesized that the elderly, who are known to have a microbiome that is relatively depleted of different bacterial species, are at a substantially increased risk of severe and fatal infections because of an unhealthy gut microbiome (a condition called dysbiosis). And it is further postulated that this age-related waning of immunity (referred to as immunosenescene) sets the stage for an inadequate defense against the SARS-CoV-2 virus.


While a number of research groups are testing the hypothesis that the composition of the gut microbiome influences the severity of COVID-19 infection, I believe that Dr. Martin Blaser, the Henry Rutgers Chair of the Human Microbiome at Rutgers University, and his research collaborators in New Jersey and the Cleveland Clinic are the most likely to provide meaningful results in the near future. These researchers have collected and stored 25,000 fecal microbiota specimens from patients collected before they developed COVID-19. Should they find that the gut microbiome influences the severity of COVID-19, the next step will be to determine if restoring its diversity is another public health measure that protects us against SARS-CoV-2.


In support of the idea that the gut microbiome influences the severity of COVID-19, last September in the journal Gastroenterology, a University of Hong Kong research team reported an association between the bacterial composition of the gut microbiome, inflammatory biomarkers in the blood, and the severity of COVID-19. In addition, they found preliminary evidence of a potential link between the gut microbiome and prolonged symptoms (what’s now referred to as “long COVID-19”).

Are there ways to modulate the gut microbiome? As evidence continues to accumulate supporting the role of the psychobiome in medical conditions that are in need of non-pharmacological treatments, such as, depression, anxiety, sleep disorders, and cognitive and eating disorders, researchers are beginning to explore methods that modulate the gut microbiome to treat these conditions. Of the modalities studied so far, fecal microbiota transplantation (FMT) has captured the most attention. (For a review of this topic, see Jennifer Wargo’s review in the September 2020 issue of Science, “Modulating gut microbes: Fecal microbiota transplant and modulation of microbial species show therapeutic promise.”) And the good news about FMT is that many clinical groups are administrating fecal microbiota orally (“poop in a pill”) rather than via colonoscopy or other relatively invasive techniques.


Another method of altering the gut microbiome is through the use of probiotics (“live microorganisms which when administered in adequate amounts confer a health benefit on the host”). Professor Ng Siew-chien, Associate Director of the Centre for Gut Microbiota Research at the Faculty of Medicine of The Chinese University of Hong Kong has developed a probiotic formula she suggests will help to increase the good bacteria in the human gut thereby adding to our arsenal in the fight against the novel coronavirus. The topic of the risks and benefits of probiotics is complex and is deserving of review in a future Germ Gem post, so stay tuned. But if other research groups confirm the role of the gut microbiome in determining the course of COVID-19, we can anticipate a “shitload” of interest in this approach to fighting viruses, like SARS-CoV-2!

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

 

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