Why Are Post-COVID Mental Wellness Problems So Common?

Nice article in Apple News apple.news/A0j3CoGB3QLykSI2_M_fZdg

Interesting how post-COVID symptoms include so many brain and mental wellness issues – suggesting that COVID is not just an infection of the lungs and upper respiratory tract, but also for the nervous system, brain, immune system, inflammatory system and the gut – it is damaging the entire Gut-Brain-Heart-Axis and leading to long-term symptoms of depression, anxiety, brain fog, and burnout.

My next book, The Mental Fitness Diet, discusses how to optimize health from our microbiome to our brain across the entire Gut-Brain-Heart-Axis (which includes the immune system) – and might just turn out to be a “COVID-control” program as much as it is a “mental fitness” program?

Long after the fire of a Covid-19 infection, mental and neurological effects can still smolder

Early on, patients with both mild and severe Covid-19 say they can’t breathe. Now, after recovering from the infection, some of them say they can’t think.

Even people who were never sick enough to go to a hospital, much less lie in an ICU bed with a ventilator, report feeling something as ill-defined as “Covid fog” or as frightening as numbed limbs. They’re unable to carry on with their lives, exhausted by crossing the street, fumbling for words, or laid low by depression, anxiety, or PTSD.

As many as 1 in 3 patients recovering from Covid-19 could experience neurological or psychological after-effects of their infections, experts told STAT, reflecting a growing consensus that the disease can have lasting impact on the brain. Beyond the fatigue felt by “long haulers” as they heal post-Covid, these neuropsychological problems range from headache, dizziness, and lingering loss of smell or taste to mood disorders and deeper cognitive impairment. Dating to early reports from China and Europe, clinicians have seen people suffer from depression and anxiety. Muscle weakness and nerve damage sometimes mean they can’t walk.

“It’s not only an acute problem. This is going to be a chronic illness,” said Wes Ely, a pulmonologist and critical care physician at Vanderbilt University Medical Center who studies delirium during intensive care stays. “The problem for these people is not over when they leave the hospital.”

Doctors have concerns that patients may also suffer lasting damage to their heart, kidneys, and liver from the inflammation and blood clotting the disease causes.

No one can yet tell patients with neurological complications when, or if, they’ll get better, as doctors and scientists strive to learn more about this coronavirus with each passing day. Their guideposts are the experience they’ve gained treating other viruses and delirium after ICU stays, sparse results from brain autopsies, and interviews with patients who know something is just not right.

“We would say that perhaps between 30% and 50% of people with an infection that has clinical manifestations are going to have some form of mental health issues,” said Teodor Postolache, professor of psychiatry at the University of Maryland School of Medicine. “That could be anxiety or depression but also nonspecific symptoms that include fatigue, sleep, and waking abnormalities, a general sense of not being at your best, not being fully recovered in terms of the abilities of performing academically, occupationally, potentially physically.”

John Bonfiglio, 64, counts himself among the fortunate ones. He remembers nothing between sitting in Newton-Wellesley Hospital’s emergency department with a fever and waking up 17 days later in the Massachusetts hospital’s ICU. He’d been on a ventilator, lying prone until his failing kidneys meant he needed to be flipped over onto his back for dialysis. Weak and confused from his ordeal after moving to a regular hospital floor, he tried to slip around his bed’s guardrails and slid to the floor. Nurses would routinely ask his name and if he knew where he was. One day he answered “Las Vegas.”

Bonfiglio chalks that up to post-ICU disorientation that included his feeling more emotional. Ordinarily “not a crier,” as he put it, he would choke up sometimes. More troubling were the persistent dizziness, muscle weakness, and tremors in his hands that made it impossible to put his contact lenses in his eyes.

He was discharged to Spaulding Rehabilitation Hospital in nearby Charlestown, Mass., where he spent the balance of his 51-day hospitalization — during which he saw no family members since suggesting to his daughter that she go home from the emergency room that night in April.

From his early days in rehab, when sitting up in bed was exhausting, to learning how to walk again with a walker, to finally going home to Waltham, Mass., Bonfiglio lost 40 pounds — “all muscle.” He’s regained some of his strength, and weight, now. His dizziness and tremors are gone. And his mind is clear.

He’s back driving part-time for a food-delivery service, and he jokes that being in a drug-induced coma meant he missed the pandemic’s surge in Massachusetts. When he visited the Newton-Wellesley ICU after a checkup, he couldn’t remember any of the staff there. He does remember what one nurse said as he was leaving the hospital for Spaulding: “‘You are the first person that is going to rehab and not to hospice,’ she told me. So I feel extremely lucky, you know, just making it through.”

Vanderbilt’s Ely worries about patients who emerge from the ICU with more serious problems than Bonfiglio’s, including delirium caused by high-potency drugs like benzodiazepines and nerve damage from low oxygen levels.

“And then they’re getting isolated. When they’re isolated and away from family, it makes it worse,” Ely said. Later, “they’re having either post-traumatic stress disorder, anxiety disorder, depression, or cognitive impairment, and some combination of all of that. So these people are really in for some neurologic and mental health problems.”

Right now, there is little that researchers can say definitively about how best to prevent and treat neuropsychological manifestations of Covid-19. Nor do they know for certain why the brain is affected.

“It’s sort of like you’re trying to put out the fire and then a little bit later, you go look at the nervous system as the embers,” said Victoria Pelak, professor of neurology and ophthalmology at the University of Colorado School of Medicine. “Because you are so concerned with the raging fire, you haven’t really been able to pay attention to the nervous system as much as you normally would.”

She and others are piecing the story together. So far the virus appears to cause its damage to the brain and nervous system not as much through direct infection as through the indirect effects of inflammation. Pieces of the virus, not actual viruses multiplying, can trigger an inflammatory response in the brain, said Lena Al-Harthi, chair of the Department of Microbial Pathogens and Immunity at Rush Medical College.

“If you have an uncontrolled level of inflammation, that leads to toxicity and dysregulation,” she said. “What I am concerned about is long-term effects, obviously in the people who have been hospitalized, but I think it’s definitely time to understand long-term sequelae for those individuals who have never been hospitalized. They’re young, too. We’re not talking about [only] older individuals, but people that are 30.”

Fred Pelzman, who practices internal medicine in New York City, fell sick with Covid-19 in March but has yet to recover fully. He doesn’t have his wind back, or his normal sense of taste and smell. His patients who have had Covid-19 are suffering from varying degrees of depression, anxiety, or Covid fog. One can’t do simple math calculations in her head any more. Others don’t feel as mentally sharp, struggling to find the right words to say. His colleagues tell him their patients, too, dread being reinfected with the virus.

“It’s hard to separate the physical from the psychological score, and we know they are intimately related,” he said. “It’s hard to separate the Covid-19 signal from the social justice upheaval and global warming and politics and the pandemic and anxiety of just being, you know, isolated and working at home and economic turmoil and all the rest.”

Neurocognitive testing, psychiatric evaluation, and diagnostic imaging might help determine the cause for these problems, Pelzman said, but not having a baseline for comparison could make that challenging, especially when hospitals are racing to keep patients breathing and prevent blood clots from forming and clogging blood vessels or triggering strokes — common problems caused by Covid-19.

“Strokes are larger, potentially more damaging with this disorder. Once inflammation or blood vessel problems occur within the nervous system itself, those people will have a lot longer road to recovery or may die from those illnesses,” Colorado’s Pelak said.

Doctors are also watching for a syndrome called demyelination, in which the protective coating of nerve cells is attacked by the immune system when there is inflammation in the brain. As in the autoimmune disease multiple sclerosis, this can cause weakness, numbness, and tingling. It can also disrupt how people think, in some cases spurring psychosis and hallucinations. “We’re just not sure if this virus causes it more commonly than other viruses,” Pelak said.

In Italy, three Covid-19 patients with no previous history of neurologic or autoimmune disorders developed myasthenia gravis, a disease that weakens the arm and leg muscles, causes double vision, and leads to difficulties speaking and chewing. While such symptoms could follow the viral infection of nerve cells, it’s also possible that an autoimmune mechanism — the body attacking healthy cells — is at work, the group reporting these cases said.

Recovery from Covid-19 often begins in rehab. Ross Zafonte, chief medical officer at Spaulding, said he is seeing some patients’ cognitive and brain-related issues last for much longer than expected. That includes depression, memory disorders, and PTSD, as well as muscle and peripheral nerve damage that makes mobility difficult. For some patients, their mental awareness has been slow to recover.

“We’re trying to follow people long term and do a longitudinal study to see what are the comorbid factors,” he said. “What are the characteristics of people who don’t get back to normal? How can early intervention try to deal with that? Are there some biomarkers of risk? Can we try to define better targets for early intervention?”

Maryland’s Postolache thinks Covid-19 infection might act as a “priming event” for problems to resurface in the future. Psychological stress could reactivate behavioral and emotional problems that were initially triggered by the immune system responding to the virus. “What we call psychological versus biological may actually be quite biological,” he said. “We don’t really say this is permanent … but considering all complexities of human life, it’s unavoidable.”

Ely of Vanderbilt suggests three things to do now.

“We can open the hospitals back up to the families. That’s important,” he said. “We can be aware of these problems and tell the families about them so that the families will know that this is coming. [And] we can do counseling and psychological help on the back end.”

Strong Microbiome Protects Against COVID-19?

Very nice article in the GMFH Newsletter (gut microbiota for health) about the relationships between our gut microbiota and COVID-19.

You can read the original article HERE and see my highlighted version with comments below.

What do we know about the relationship between our gut microbiota and COVID-19

COVID-19 primarily attacks the respiratory system. However, the links between the latter, your digestive tract and immune system make an examination of the role of nutrition and the gut microbiota in the fight against the virus relevant. (DocTalbott note = the links across the Gut-Brain-Axis show very strong relationships between what happens in the GUT (overall digestive function, gut integrity, and microbiome balance); and what happens in the BRAIN (including focus, stress response and overall mood); and these signals are transmitted across the AXIS (including the immune system and inflammatory cascade).

It is hardly news that one important way by which the new coronavirus strain (called SARS-CoV-2) affects people’s health is by weakening the respiratory tract, from the nose to the lungs.

But as scientists become more familiar with the virus, they are also finding out that the body’s immune and digestive systems might be also affected.

Why it is worth taking the gut microbiota into account in the fight against COVID-19

The idea that bodily organs and tissues opened to the outside are connected is not new. For instance, the lungs and gut microbiota influence each other and that relationship may keep your lungs healthy. (DocTalbott note = some of our research has shown that improvements in gut-brain-axis and heart-brain-axis parameters also improve lung function)

In this case, scientists have reported the presence of SARS-CoV-2 in the stool samples of people who have the virus. Furthermore, some COVID-19 patients showed an altered gut microbiota composition with decreased beneficial bacteria, which included Lactobacillus and Bifidobacterium.

“[Although] there is no way our gut microbiome could exert direct protection against COVID-19, we have very good evidence that there is a very close relationship between the microbiota and the immune system. A balanced healthy microbiota promotes immune homeostasis*, hence avoiding hyper-reactivity [of a person’s immune system],” acknowledged INRAE Research Director Joël Doré via email.

A healthy gut microbiome could prevent immune overreactions to COVID-19

Considering the gastrointestinal manifestations of the COVID-19 infection and the gut microbiota’s role in the body’s immune response to viral infections, scientists suspect that a healthy gut microbiome might help prevent pro-inflammatory immune reactions in the lungs and other vital organs infected by COVID-19.

“Taking care of our gut health and especially nurturing a highly diverse microbiota through a dietary intake rich in a wide range of plant sources, fruits, vegetables, grains and nuts will favor a robust immune system and indirectly increase our ability to fight viral attacks in every organ, including the lungs,” highlighted Joël Doré.

How might probiotics and prebiotics fare in fighting the current coronavirus pandemic?

Within diet, probiotics and prebiotics may play an important role in regulating the functioning of the immune system’s response via the gut microbiota, which in turn influences the immune system.

While probiotics have been shown to reduce flu-like respiratory tract infections, China’s National Health Commission and National Administration of Traditional Chinese Medicine suggested the use of probiotics in patients with severe COVID-19 to prevent secondary bacterial infection.

Joël Doré acknowledged: “In addition to a diverse protective commensal microbiota, certain strains of probiotics are known to exert activities that empower the immune system. They have their place in a preventive arsenal, together with appropriate nutrition and gut-barrier reinforcing, anti-inflammatory and anti-oxidant strategies.”

Like probiotics, fermentable dietary fiber could also optimize immune defense against viral infections, as revealed by a mice study in which a day diet high in soluble fiber led to a reduced lung viral load and increased survival.

Although what you eat won’t stop you getting infected with COVID-19, looking after your gut microbiota with a well balanced diet that includes probiotics and prebiotics when necessary for supporting digestive wellbeing will help keep your immune system in good shape.

*Gut immune homeostasis is the state in which our immune system protects us from pathogens while remaining harmless against our microbiota, food and other environmental components.

References:

Kissler SM, Tedijanto C, Goldstein E, et al. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic periodScience. 2020; eabb5793. doi: 10.1126/science.abb5793.

Pan L, Mu M, Yang P, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter studyAm J Gastroenterol. 2020; 115. doi: 10.14309/ajg.0000000000000620.

Enaud R, Prevel R, Ciarlo E, et al. The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalksFront Cell Infect Microbiol. 2020; 10:9. doi: 10.3389/fcimb.2020.00009.

Xu K, Cai H, Shen Y, et al. Management of corona virus disease-19 (COVID-19): the Zhejiang experienceZhejiang Da Xue Xue Bao Yi Xue Ban. 2020; 49(1):0.

Gou W, Fu Y, Yue L, et al. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. doi: 10.1101/2020.04.22.20076091 [Preprint]. 2020 [cited 2020 April 27]. Available from: https://www.medrxiv.org/content/10.1101/2020.04.22.20076091v1

Mak JWY, Chan FKL, Ng SC. Probiotics and COVID-19: one size does not fit allLancet Gastroenterol Hepatol. 2020. doi: 10.1016/S2468-1253(20)30122-9.

COVID-19, Immunity and Inflammation

Writing last week in the NY Times (May 25), Jane Brody brought up a number of excellent points (as she always does) about how people can improve their health.

In this case, the focus was on COVID-19, which is an important topic considering that all 50 states are in some stage of post-quarantine “re-opening” – and with growing numbers of people interacting at the important civil rights protests, we ALL need to be aware of what we can do to protect ourselves (and others) from COVID-19 transmission, infection, and adverse effects.

You can read Jane’s excellent original article HERE – and see my bolded highlights and red comments below.

To Fight Covid-19, Don’t Neglect Immunity and Inflammation

After seeing who is most likely to become infected and die, immunity and inflammation warrant further discussion and public attention.

While most people focus, as they should, on social distancing, face coverings, hand washing and even self-isolation to protect against the deadly coronavirus now ravaging the country, too few are paying serious attention to two other factors critically important to the risk of developing a Covid-19 infection and its potential severity.

Those factors are immunity, which should be boosted, and inflammation, which should be suppressed. (DocTalbott note = a better way to explain this would be to “balance” both – because you actually don’t want an “over-active” immune response or an “underactive” inflammatory response)

I’ve touched on both in past columns, but now that months of pandemic-related restrictions have impacted the lives of millions, and after seeing who is most likely to become infected and die, immunity and inflammation warrant further discussion and public attention.

One fact is indisputable: Older people are especially vulnerable to this disease and its potentially fatal consequences. But “older” doesn’t necessarily mean “old.” While people over 80 are 184 times more likely to die from Covid-19 than those in their 20s, Dr. Nir Barzilai, scientific director of the American Federation for Aging Research, points out that vulnerability increases starting around age 55.

Immune defenses decline with age. (DocTalbott note – so in this case of age-related immune suppression, you might want to “boost” immune system function – but only back to normal levels – what I would refer to as “priming” immune response so you get an appropriate level of protection, but not so much immune activity that you start to see auto-immune side effects such as allergies and food intolerances and other instances of the immune system attacking healthy body tissues). That is a fundamental fact of biology. For example, with advancing age, natural killer cells, a major immunological weapon, become less effective at destroying virus-infected cells. But it doesn’t mean nothing can be done to slow or sometimes even reverse immunological decline, said Dr. Barzilai, who directs the Institute for Aging Research at Albert Einstein College of Medicine.

At the same time, inflammation in tissues throughout the body increases with age, a fact that helps the coronavirus get into the body, bind to molecules in the nose and lungs, and wreak havoc, Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham in England, explained in a webinar this month. (DocTalbott note = same idea here – that you might want to reduce inflammation from “high” back “down” to normal – but you don’t want to push inflammation too low because a certain amount of inflammation is also protective against tissue damage and helps promote tissue repair – it’s all about the balance and ensuring that both our immune response and inflammatory reaction are dynamic so they can respond in a just right “Goldilocks” fashion – not too little or too much).

Fat tissue, for example, increases inflammation and renders overweight people more vulnerable to a Covid infection.

Here, too, there are established ways to diminish inflammation and thereby enhance resistance to this deadly disease. The basic weapons, diet and exercise, are available to far more people than currently avail themselves of their benefits. Lifestyle can have a major impact on a person’s immune system, for better or worse, Dr. Lord said.

I spoke recently to a friend who “escaped” New York City in early March to avoid Covid-19. But while he reduced his risk of infection by limiting contact with other people, he has gained weight, lost muscle mass and, in becoming nearly sedentary, is also now more likely to become seriously ill if he should contract the virus.

Skeletal muscle helps the immune system,” Dr. Lord said. The contractions of skeletal muscles produce small proteins called myokines that, by dampening inflammation, have big health benefits. Myokines ferret out infections and keep inflammation from getting out of hand, she said. Also, exercising skeletal muscle helps diminish body fat and increases the potency of natural killer cells no matter what your age. An 85-year-old who increases muscle mass is better able to recover from Covid, she said. (DocTalbott note – this is one of the many reasons that we see regular exercisers having a dramatically reduced infection risk during cold/flu season – even if they are in contact with many other people).

The more extensive or vigorous the exercise, the less inflammation, Dr. Lord said. (DocTalbott note – up to a point – if you go beyond your training level, such as running a marathon, and “over-stress” your system, you’re actually much more likely to experience a temporary immune suppression and over-inflammation, which increases your risk for respiratory infections. This is why about half of all marathon finishers will catch a cold in the week following the event). She noted that those who do fewer than 3,000 steps a day have the highest level of inflammation, whereas those who do 10,000 or more steps daily have the least inflammation. But social isolation doesn’t have to make you a couch potato.

“You don’t need any special equipment,” she said, so the inability to go to a gym or even outside need not be an impediment to getting in those 10,000 steps. She suggested exercises like heel raises, leg raises and sit-to-stand exercises. You could even use two of those cans of beans you stocked up on to strengthen arm muscles. Or consider going up and down stairs, or even one step, which has the added benefit of strengthening heart function. For other ideas, see Gretchen Reynolds’s column published in The Times on April 22.

Exercise is especially important for people with chronic health conditions that increase their vulnerability to a serious Covid infection. “No matter what your condition, exercise will improve your immunity,” Dr. Lord said.

Regular exercise can also improve your sleep, which can suppress inflammation and keep your immune system from having to work overtime. (DocTalbott note – the chronic stress of sleep deprivation is particularly insidious for the immune system and for systemic inflammation – getting enough high-quality sleep and balancing your stress levels might be the best way to protect yourself from COVID-19 infection). Aim for seven to eight hours of sleep a night. If virus-related anxieties keep you awake, try tai chi, meditation or progressive muscle relaxation (from feet to head) to reduce stress and calm your mind and body. Avoid eating a big meal late in the day or consuming caffeine after noon. Perhaps eat a banana or drink a glass of warm milk about an hour before bedtime.

Which brings me to what for many is the biggest health challenge during the coronavirus crisis: consuming a varied, nutrient-rich diet and keeping calorie intake under control. It seems baking has become a popular pastime for many sheltering at home, and the consequences — weight gain and overconsumption of sugar and refined flour — can increase susceptibility to the virus. Excess weight weakens the immune system, and abdominal fat in particular enhances damaging inflammation.

The good news, according to Dr. Leonard Calabrese, clinical immunologist at the Cleveland Clinic, is that even small amounts of weight loss can counter inflammation, a benefit aided by avoiding highly processed foods and eating more fresh fruits and vegetables that are relatively low in calories and high in protective nutrients.

Especially helpful are foods rich in vitamin C — all manner of citrus (oranges, grapefruit, clementines, etc.), red bell pepper, spinach, papaya and broccoli — and zinc, including shellfish (oysters are a powerhouse of zinc), seeds, dairy products, red meat, beans, lentils and nuts.

For those who drink alcohol, these stressful times can tempt overconsumption. More than the recommended two drinks a day for men and one for women can reduce immunity-boosting nutrients in the body and impair the ability of white blood cells to fight off microbial invaders, Dr. Calabrese notes. For those who drink, a five-ounce serving of red wine a day is widely considered a beneficial component of an anti-inflammatory Mediterranean-style diet.

Reports linking a deficiency of vitamin D to an increased risk of developing a severe Covid-19 infection have prompted some people to take measures that may ultimately undermine their health, like basking unprotected in the sun, which can lead to skin cancer, and taking excessive amounts of a vitamin D supplement, which can cause distressing gastrointestinal symptoms.

Healthy blood levels of vitamin D can, though, help keep the body’s immune system strong and possibly help prevent it from raging out of control, causing the cytokine storm that can severely damage the lungs and other tissues and has resulted in many Covid-19 deaths. But for those with already healthy levels of vitamin D, there’s no established immune benefit from taking more than 2,000 IU of vitamin D-3 a day.

DocTalbott note = as we all head back out into the world, we need to keep in mind that this is NOT a “post-COVID-19” world. Rather, it is very much a world where COVID-19 is all around us, and just as virulent and deadly as it was 3 months ago. This is not a reason to panic, but rather a reason to be smart and vigilant about keeping our immune system properly primed and our inflammatory system properly balanced. I write about these topics extensively on this blog and talk about them on my YouTube channel.

Psychobiotics Going Mainstream?

Last week, the science journal/magazine, Science (one of the leading scientific publications on the planet) ran an excellent article on the “Psychobiome” (gut bacteria – aka the “microbiome” – that are involved in psychological effects such as stress, mood, and anxiety).

Since I’ve been researching and writing about this area for many years – and developing natural products to optimize the microbiome for improved mood, reduced stress, and enhanced mental fitness (aka “nutritional psychology”), I found this article to be just what the doctor ordered for the stressful times we’re all living in – I hope you do as well?

You can read the full original article here and see a highlighted version with my notes below.

Bacterial residents of the intestines may influence neurons and the brain through several routes.

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Meet the ‘psychobiome’: the gut bacteria that may alter how you think, feel, and act
By Elizabeth Pennisi (May. 7, 2020)

CAMBRIDGE, MASSACHUSETTS—Katya Gavrish is searching for new brain drugs in a seemingly unlikely place: human stool samples. An earnest and focused microbiologist who trained in Russia and loves classical music, she’s standing in front of a large anaerobic chamber in a lab at Holobiome, a small startup company here. She reaches into the glass-fronted chamber through Michelin Man–like sleeves to begin to dilute the sample inside. That’s the first step toward isolating and culturing bacteria that Gavrish and her Holobiome colleagues hope will produce new treatments for depression and other disorders of the brain and nervous system. (DocTalbott note = it’s difficult to over-emphasize how much impact the microbiome has on the brain)

The eight-person company plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimer’s disease. Since its founding a mere 5 years ago, Holobiome has created one of the world’s largest collections of human gut microbes. The company’s CEO, Phil Strandwitz, cannot yet say exactly what form the new treatments will take. But the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndrome—conditions that may have neurological as well as intestinal components. Strandwitz, a mild-mannered Midwesterner with a Ph.D. in microbiology, isn’t prone to visionary statements, but neither is he short on ambition: He predicts the first human trial will start within 1 year. (DocTalbott note = our group has already conducted/presented/published several human trials showing how specific probiotic/prebiotic/phytonutrients can dramatically improve mood states including depression, anxiety, tension, and others)

The allure is simple: Drug development for neuropsychiatric disorders has lagged for decades, and many existing drugs don’t work for all patients and cause unwanted side effects. A growing number of researchers see a promising alternative in microbe-based treatments, or “psychobiotics,” a term coined by neuropharmacologist John Cryan and psychiatrist Ted Dinan, both at University College Cork. “This is a really young and really exciting field with a huge amount of potential,” says Natalia Palacios, an epidemiologist at the University of Massachusetts, Lowell, who is looking into connections between gut microbes and Parkinson’s disease.

Some researchers prefer a less hurried approach focused on understanding the underlying biology. But Holobiome and a few other companies are eager to cash in on the burgeoning, multibillion-dollar market that has already sprung up for other microbial therapies, which aim to treat conditions including intestinal disorders, allergies, and obesity. Those companies are pushing ahead despite many unresolved questions about how psychobiotic therapies might actually work and the potential dangers of moving too fast. “There’s a gold rush mentality,” says Rob Knight, a microbiologist at the University of California (UC), San Diego.

OVER THE PAST 20 YEARS, the recognition that the microbes living inside us outnumber our body’s own cells has turned our view of ourselves inside out. The gut microbiome, as it’s known, weighs about 2 kilograms—more than the 1.4-kilogram human brain—and may have just as much influence over our bodies. Thousands of species of microbes (not only bacteria but also viruses, fungi, and archaea) reside in the gut. And with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes can’t match. Gut bacteria can make and use nutrients and other molecules in ways the human body can’t—a tantalizing source of new therapies.

The brain is the newest frontier, but it’s one with an old connection to the gut. The ancient Greeks, for example, believed mental disorders arose when the digestive tract produced too much black bile. And long before microbes were discovered, some philosophers and physicians argued that the brain and gut were partners in shaping human behavior. “What probably happens is that our brain and our gut are in constant communication,” says Cryan, who over the past decade has helped drive efforts to decode those communications. (DocTalbott note = think of all the terminology that we use everyday about having “gut feelings” or “trusting your gut” – and the new science of the microbiome is teasing out these effects that we’ve been observing since the beginning of time)

Epidemiological researchers have turned up intriguing connections between gut and brain disorders. For example, many people with irritable bowel syndrome are also depressed, people on the autism spectrum tend to have digestive problems, and people with Parkinson’s are prone to constipation.

Researchers have also noticed an increase in depression in people taking antibiotics—but not antiviral or antifungal medications that leave gut bacteria unharmed. Last year, Jeroen Raes, a microbiologist at the Catholic University of Leuven, and colleagues analyzed the health records of two groups—one Belgian, one Dutch—of more than 1000 people participating in surveys of their types of gut bacteria. People with depression had deficits of the same two bacterial species, the authors reported in April 2019 in Nature Microbiology.

Researchers see ways in which gut microbes could influence the brain. Some may secrete messenger molecules that travel though the blood to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Bacterial molecules might relay signals to the vagus through recently discovered “neuropod” cells that sit in the lining of the gut, sensing its biochemical milieu, including microbial compounds. Each cell has a long “foot” that extends outward to form a synapse-like connection with nearby nerve cells, including those of the vagus.

Indirect links may also exist. Increasingly, researchers see inflammation as a key factor in disorders such as depression and autism. Gut bacteria are key to proper immune system development and maintenance, and studies show that having the wrong mix of microbes can derail that process and promote inflammation. And microbial products may influence what are known as enteroendocrine cells, which reside in the lining of the gut and release hormones and other peptides. Some of those cells help regulate digestion and control insulin production, but they also release the neurotransmitter serotonin, which escapes the gut and travels throughout the body. (DocTalbott note = because of all these interacting factors, we also need to look beyond “just” the microbiome to also include each layer of the entire Gut-Brain-Axis, which gives us targets at the level of the microbiome, and at the level of the gut environment, and the level of the gut lining, and the immune system, and the inflammatory cascade, etc)

Although the mechanisms remain elusive, animal studies by Cryan and others have bolstered the idea that gut microbes can influence the brain. Rats and mice given fecal transplants from people with Parkinson’s, schizophrenia, autism, or depression often develop the rodent equivalents of those problems. Conversely, giving those animals fecal transplants from healthy people sometimes relieves their symptoms. The presence or absence of certain microbes in young mice affects how the mice respond to stress as adults, and other mouse studies have pointed to a role for microbes in the development of the nervous system.

At their lab, Cryan, Dinan, and their colleague Gerard Clarke think the amino acid tryptophan, which some gut bacteria produce, could be a causal link. Microbes or the body’s own cells can convert tryptophan into serotonin, a neurotransmitter implicated in depression and other psychiatric disorders. Cells also turn tryptophan into a substance called kynurenine, which reacts further to form products that can be toxic to neurons. Changes in the microbiome might tip the production of those various substances in a way that impairs mental health, Cryan says. Research has shown, for example, that people with depression convert tryptophan into kynurenine more readily than into serotonin.

Cryan’s group has amassed scores of papers and reviews that have helped solidify the case for microbial effects on several psychological and neurological disorders. But teasing effective fixes out of those links will be difficult, Clarke says: “It is one thing to know that a particular aspect of host physiology is influenced by our gut microbes and quite another to bend this influence to our will.”

Clarke’s group collaborates and consults with many companies and has tested some potential psychobiotics for stress management in healthy volunteers. But he sees a long road to treatments. “It will be important to understand better and more precisely the mechanisms at play.”

HOLOBIOME ISN’T AS PATIENT. Strandwitz founded the company in 2015 while still a graduate student in Kim Lewis’s microbiology lab at Northeastern University. “He very politely told me that he would join the lab only if I helped him start a company once he graduated,” recalls Lewis, who is famous for discovering and working to commercialize new antibiotics from soil microbes. Lewis agreed, but he figured it would be 10 years or more before Strandwitz would have his own company. Lewis was wrong: It only took 4 years.

At Northeastern, Strandwitz learned what he calls the “art of cultivation” from Gavrish, who was working with Lewis on isolating soil microbes. At the time, only about 25% of gut bacteria could be grown in the lab. Gavrish, who specializes in isolating and describing new microbial species, taught Strandwitz to manipulate nutrients and use antibiotics to give slow-growing, picky bacteria a chance to survive in culture instead of being outcompeted by more aggressive species. He began to track down growth factors to keep recalcitrant species going. Now, Strandwitz says, “We have in culture about 70%” of the known human gut microbes. If true, it’s a figure few other labs can match.

One growth factor Strandwitz identified turned out to be the key to launching his entrepreneurial dreams. He and colleagues isolated a bacterium that couldn’t survive on typical culture media and required an amino acid called gamma-aminobutyric acid (GABA) to thrive. GABA is a neurotransmitter that inhibits neural activity in the brain, and its misregulation has been linked to depression and other mental health problems.

The researchers reasoned that if this gut microbe had to have GABA, some other microbe must be making it. Such GABA producers might be a psychobiotic gold mine. Strandwitz and colleagues began to add gut microbes one at a time to petri dishes containing the GABA eater. If the GABA eater thrived, the scientists would know they’d found a GABA producer. They discovered such producers among three groups of bacteria, including Bactereroides. They quickly filed a patent for packaging those bacteria—or their products—to treat people with depression or other mental disorders.

Before publishing those findings, the group teamed up with researchers at Weill Cornell Medicine who were doing a brain scan study of 23 people diagnosed with depression. They found that people with fewer Bacteroides bacteria had a stronger pattern of hyperactivity in the prefrontal cortex, which some researchers have associated with severe depression. The collaboration reported its findings on 10 December 2018 in Nature Microbiology, along with the discovery of GABA-producing bacteria. (DocTalbott note = one of our very recent trials showed a substantial increase in Bacteroidetes – leading to not just improvements in mood and overall well-being, but also in body fat levels, metabolism, and cardiovascular health)

Holobiome further discovered that the bacteria produce GABA in the rat digestive tract, which may increase GABA levels in the brain. And it found that GABA producers reduced learned helplessness—a symptom of depression—in those animals. One of Strandwitz’s co-authors, microbial ecologist Jack Gilbert at UC San Diego, is also testing the therapeutic potential of GABA-producing bacteria in rats. His group and Holobiome have both observed that treated rats are more likely to stay longer on an uncomfortably warm surface—a test of visceral pain tolerance—perhaps because elevated GABA calms them. The findings are unpublished, but they’ve persuaded Gilbert to investigate whether those bacteria can also reduce anxiety in rats. “It’s clear they do have a neuromodulatory effect,” he says.

GABA is too big to reach the brain by slipping across the blood-brain barrier, a cellular defense wall that limits the size and types of molecules that can get into the brain from blood vessels. Instead, the molecule may act through the vagus nerve or the enteroendocrine cells. Some researchers might question why bacteria would be any more beneficial than GABA-boosting drugs. But Strandwitz says the bacteria may do more than simply boost GABA. He notes that they produce molecules that may have other effects on the brain and body, thereby addressing other symptoms of depression. (DocTalbott note = getting your microbiome to produce more GABA is a great way to reduce stress, tension, and anxiety – but what if you could also get your microbiome to make more dopamine so you’re more energized and motivated – or more serotonin so you’re happier and more content – or more norepinephrine so you can concentrate and focus – the list of potential benefits goes on and on – and most of them are achievable naturally)

He and Gilbert are unfazed by those uncertainties. “If we can show an influence, without any side effects, I don’t see any reason for not going forward with clinical trials,” Gilbert says.

At Holobiome, Strandwitz and colleagues have identified and ranked 30 promising GABA-producing bacteria, including the ones Gilbert is testing. Now, the company is enlisting an outside manufacturer to figure out which GABA-producing bacteria are best suited to produce in large enough quantities to test in people. The researchers hope to complete regulatory and ethical reviews in time to start human trials by early 2021. “We’ve been able to progress at this rate because we know our microbiology,” Strandwitz says. The initial target conditions are insomnia and irritable bowel syndrome with constipation.

Ultimately, Holobiome does not know whether its best products will be a single bacterial species, a group of species, or a compound made by bacteria. “For now, live bugs work the best,” Strandwitz says. He suggests a consortium of bacteria that includes a wider range of species than typical probiotics will be more versatile and able to treat multiple aspects of, say, depression.

HOLOBIOME IS ALREADY LOOKING beyond GABA producers. Thousands of newly isolated microbes wait in frozen vials at the company’s headquarters for their psychobiotic potential to be explored. “Whenever we see someone publishes a new paper on the microbiome, we can check if we have those bacteria and replicate the experiments,” says Holobiome’s Stephen Skolnick, who recently joined the company.

A key tool for those experiments is a “gut simulator,” a series of flasks connected by tubing, with several portals for adding microbes and for monitoring what’s happening inside. By allowing a mock microbiome to develop from different combinations of bacteria, sometimes with mammalian cells in the mix, the researchers can investigate newly isolated microbes and their products. If the scientists see promise, they can quickly pivot to thinking about additional products to develop.

Skolnick took the lead on obtaining a patent for Holobiome’s use of queuine—a vitamin-like molecule only produced by certain gut microbes—to improve mental well-being. The body uses queuine to build neurotransmitters such as dopamine, serotonin, and melatonin. Whether adding queuine producers or the molecule itself to the gut might help people with mental illness isn’t clear, but Strandwitz says he’s excited about the idea.

“It’s been amazing to witness the tremendous growth in the microbiome gut-brain field,” says UC Los Angeles biologist Elaine Hsiao. Like Strandwitz, she is an enthusiast, having helped start two companies to develop microbial therapies for several disorders, including epilepsy and autism.

Other researchers fear entrepreneurship is outracing science. Knight says venture capitalists are funding startups developing almost any microbiome-based therapies. Some concepts are “very promising and are supported by a lot of evidence,” he says, but others aren’t, and they’re still getting money. Knight says investors see an opportunity in eager patients. (Raes says he gets almost daily emails from depressed people seeking help.)

Microbial therapies won’t necessarily meet the same standards of efficacy as regular drugs. To be marketed as a pharmaceutical, a treatment has to pass muster with the U.S. Food and Drug Administration, or its equivalent in other countries, through clinical trials that prove its effectiveness against specific diseases. Most microbiome treatments so far are marketed as probiotics, for which regulatory thresholds are lower, at least in the United States—as are limits on the health claims that a manufacturer can make. Holobiome is developing both types of products.

The field still faces considerable scientific questions, too. Besides the correlative nature of much of the research and the usual questions of whether animal studies will translate to humans, there’s also the sheer complexity of the human microbiome, says Beatriz Peñalver Bernabé, a systems reproductive biologist at the University of Illinois, Chicago. “I don’t think that it will be ‘one thing fits all.’ We will need to look for specific strains and dosages for different people.” And, she adds, new theories and models are needed to predict how those strains will affect the individual’s particular microbiome community. (DocTalbott note = imagine the day where we can quickly, easily, and inexpensively measure your own personal microbiome – and provide you with a customized approach to microbiome modulation that is trackable over time to help you toward your goals or better mood – or less stress – or improved sleep – or weight loss – or anti-aging, etc. Those days are closer than you may think…)

Despite the obstacles, Gavrish remains confident that some strains she’s growing in the anaerobic chamber will lead to treatments. After all, she says, the connection between gut microbes and the human brain has deep evolutionary roots. “I truly believe you can harness the power of a million years of signaling by gut bacteria to help people.” (DocTalbott note = Agreed – the future of health is ancient)

Microbiome, Stress, and Immunity

Please join me and Michael Quach TONIGHT at 6pm PT for a discussion about how supporting your Microbiome can act as a “stress vaccine” to improve both Mental Wellness (stress, anxiety, depression, burnout) and Physical Health (immune protection, inflammation, and overall wellness).

Zoom = https://zoom.us/j/9292793215

Amare Facebook = https://www.facebook.com/groups/1bewell/

DocTalbott Facebook = https://www.facebook.com/doctalbott

2020ConferenceCall-ScienceofAmare-April9.jpg

Kid’s Mood+ Clinical Study

These last few days (April 4-7) should have been the annual scientific conference known as Experimental Biology in San Diego, CA.

Unfortunately, EB was cancelled due to the COVID-19 pandemic – so many of us are uploading our research to a central database that will be made available to the public in the coming days. The research abstracts will still be published in the FASEB Journal in the coming months – but I also wanted to get this information out to people ASAP, so I recorded my presentation via Zoom and posted the video to YouTube.

Here is the abstract of the study – notice our overall conclusions in red below:

Targeted Dietary Supplementation Improves Mental Performance in Children

Andrea Armstrong DC1, Michelle Massa MD2, Jessica Royston CHHC2, Markham McHenry DO3, and Shawn Talbott PhD4

1Armstrong Chiropractic and Family Wellness Center

2Advanced Natural Medicine of Jupiter, Inc.

3Elevate Health AZ

4Amare Global

Background: Saffron (Crocus sativus) dried flower stigma is the world’s most expensive spice and has been used in traditional medicine for alleviating depression, stress, anxiety, and insomnia. Saffron stigma contains more than 160 bioactive compounds including lepticrosalides (safranal, crocin, crocetin, picrocrocin) and numerous flavonoids and terpenes that have been associated with relaxation, positive mood, and mental & physical balance. At least seven controlled clinical trials have shown the antidepressant activity of saffron.

Objective: Building on the well-described “mood” benefits of saffron, our objective was to assess the benefits of saffron stigma combined with complementary brain-supporting spices (Holy Basil, Rosemary, Clove, and Oregano) on measures of mental focus and mental performance in healthy children who had not been diagnosed with either depression or ADHD.

Methods: Ten healthy children (ages 6-12 years of age) participated in this study. We used the validated NICHQ Vanderbilt Assessment Scales (National Institute for Children’s Health Quality) that are routinely used by healthcare professionals to help diagnose ADHD in children 6-12 years and are part of the American Academy of Pediatrics (AAP) Resource Toolkit for Clinicians Caring for Children with ADHD (3rd edition, 2019). Parents administered the NICHQ survey before and after 30-days of supplementation with a multi-nutrient blend intended to improve mental focus, mood, and stress resilience (Kid’s Mood+; Amare Global). The NICHQ assessment scales have 2 components: Symptom Assessment (in 5 areas: inattention, hyperactivity, defiance, conduct, and anxiety/depression) and Performance Assessment (including school performance on reading, writing, and math; as well as social relationship performance with parents, siblings, and peers including on organized teams).

Results: Following 30-days of supplementation, we found dramatic improvements on assessments of both Symptoms (e.g. focus, attention, mood, listening, tension, and irritation) and Performance (e.g. overall school work, math, reading, writing, and social relationships). All participants (10/10) demonstrated benefits in response to supplementation, with average Symptom scores 29% lower (23.4 pre versus 16.6 post) and Performance scores improved 18% (2.24 pre versus 1.83 post).

Conclusions: Previous human trials in children and teenagers have shown equivalence of saffron to fluoxetine (Prozac) for depression and methylphenidate (Ritalin) for ADHD. This is the first study in a population of normal healthy (“non-diagnosed”) children showing improvements in not just mental focus attributes, but also mental performance (academically and socially) subsequent to targeted supplementation. This study provides compelling evidence for safe and effective natural approaches as potential first-line therapy for improving focus, mood, and mental performance in children.

Stress Balance for the Whole Family

Last night, I held an online seminar about how families can naturally manage stress – for parents and kids – to help everyone feel better during these trying times…

Video is HERE on YouTube

Video is also HERE on Facebook

Slides are here = Talbott Amare Stress Focus 033120

Immune Boosting Super Foods

On April 1 (no joke!), I joined the hosts of Fresh Living on Utah’s CBS Channel 2 (virtually, of course) to discuss some of the most effective foods for supporting immune system protection.

The video is here on KUTV and here on YouTube – and below are the recipes for the smoothie and the shot that I discussed…

immune foods kutv

Immune Boosting Smoothie and Shot

With all the concern about corona virus, I will be presenting my top 10 foods for boosting immunity and helping to protect us from viruses.

Some of the top 10 foods include:

-Citrus/Kiwi (vitamin C)

-Berries (flavonoids)

-Yogurt (probiotic/beneficial bacteria)

-Seeds (prebiotic fiber)

-Mushrooms (glucans)

-Garlic (sulfur)

-Spinach (carotenoids)

-Turmeric/Ginger (turmerones/gingerols)

 

Smooth Immune (2 servings)

-2 cups of Almond milk

-1 cup of frozen berries

-1 cup vanilla yogurt

-1 cup spinach

-2 scoops Amare GBX Protein (Vanilla)

-2 scoops Amare SeedFiber (mushrooms, seed fibers)

-2 scoops Amare SuperFood (fruit/vegetable extracts)

 

Immunity Shot

-1 small orange

-1 small lemon

-1 garlic clove

-1/4 cup chopped turmeric (peeled or unpeeled)

-1/4 cup chopped ginger (peeled of unpeeled)

-Blend garlic, turmeric, ginger together first

-Add orange and lemon and blend all ingredients together into a juice

-Optional = strain pulp (I prefer to keep all the healthy fiber/pulp, but personal preference)

 

Webinar Tonight – 6pm PT

Please join me TONIGHT at 6pm PT for an overview of Amare products and the science behind improving mental wellness, optimizing gut-brain-axis balance, reducing stress, and bolstering immune protection.

 

I’ll be live on Zoom (if you want to ask questions) with simultaneous streaming to Facebook Live (if you just want to watch) – please join me at the links below…

 

Join Zoom Meeting

https://zoom.us/j/9292793215

 

Meeting ID: 929 279 3215

 

One tap mobile

+16699006833,,9292793215# US (San Jose)

+13462487799,,9292793215# US (Houston)

 

Facebook = https://www.facebook.com/groups/1bewell/

 

Gut microbiome linked to sleep quality and immune function

Interesting article and study published recently showing the close link between sleep (both quantity and quality) and the balance of the gut microbiome. Please see my highlighted version below…

The Sleep+ product that we have at Amare is the only natural approach to improving sleep quality – with ~40% more time spent in Deep Sleep (where our body rejuvenates) and REM Sleep (where our brain recovers).

With everyone these days under so much psychological stress AND wanting to improve immune system protection, any option to improve sleep quality is welcome to improve mental wellness and physical health.

Sleep quantity and quality may contribute to gut microbiota diversity

Original summary article is here = https://www.gutmicrobiotaforhealth.com/en/sleep-quantity-and-quality-may-contribute-to-gut-microbiota-diversity/

Original research study is here = Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS ONE. 2019; doi.org/10.1371/journal.pone.0222394

We already know there is a connection between sleep deprivation and a higher risk of suffering from diseases such as diabetes, obesity and cancer. Now, a new study by scientists at Nova Southeastern University (NSU) in Florida (USA) goes on to show that poor sleep is also linked to poor gut microbiota diversity, which in turns affects overall health.

“Sleep is pretty much the ‘Swiss Army Knife of health’. Getting a good night’s sleep can lead to improved health, whereas a lack of sleep can have detrimental effects,” explains Jaime Tartar, research director at NSU’s College of Psychology and co-author of the study, published in Plos One.

“Getting a good night’s sleep can lead to improved health, whereas a lack of sleep can have detrimental effects,”

The researchers undertook an experiment with 40 young healthy male volunteers, who were asked to wear a connected watch for 30 days. The device objectively monitored aspects of the quality and quantity of their sleep, taking into account factors that included bedtime, time spent in bed, total sleep time or the number of awakenings during the night.

Researchers also extracted DNA from participants’ fecal samples to examine gut microbiota diversity. We know that a more diverse gut microbiota seems to be associated with better overall health. And in this regard, Tartar highlights, a lack of gut microbiota diversity has been associated with diseases such as Parkinson’s, depression and autoimmune diseases.

After analyzing the fecal samples, the team found that the subjects who slept well had a more diverse gut microbiota and, inversely, that poor sleep was associated with decreased microbiota diversity.

A lack of gut microbiota diversity has been associated with diseases such as Parkinson’s, depression and autoimmune diseases.

“We were completely fascinated to see such strong correlation between different sleep measurements and gut microbiota diversity,” explains Tartar. “The next step is to try and understand if lower gut microbiota diversity causes poor sleep or whether, conversely, poor sleep leads to lower gut microbiota diversity. Right now we are planning a study to solve this question.”

The answer could lead to the development of potential interventions to improve gut microbiota diversity and thus, sleep quality and overall health.

Abstract of the Study:

The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examined sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome composition while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiology and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to determine how the gut microbiome correlates with various measures of sleep physiology. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome composition. We found that total microbiome diversity was positively correlated with increased sleep efficiency and total sleep time, and was negatively correlated with wake after sleep onset. We found positive correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Analysis of microbiome composition revealed that within phyla richness of Bacteroidetes and Firmicutes were positively correlated with sleep efficiency, interleukin-6 concentrations and abstract thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were negatively correlated with sleep measures. Our findings initiate linkages between gut microbiome composition, sleep physiology, the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome.