Your brains are in your belly, and that’s good for your mental health.
From depression to dementia, probiotic therapy is the revolutionary, not-so-new treatment.
Years ago, when my father was given antibiotics in hospital for a urinary tract infection, he experienced a sudden change of personality. He became delirious and started ranting. He twice called the police on his phone, convinced that the nurses were conspiring to kill him. Twice those unflappable carers had to explain to the police that no crime was underway.
How we laughed. Later, that is, when the entertainment value increased with each retelling. Fortunately, for all concerned, the delusions were only temporary. They were also intriguing. I did some research, and discovered that temporary psychosis is one of the less well-known side effects of some antibiotics.
An antibiotic is a medicine that kills bacteria. There’s your first clue.
From Fiction to Fact
There is, as I discovered, a long history of anecdotal reports of psychiatric side effects of antibiotics. Those side effects include depression, anxiety, psychosis, and mental confusion.
Until recently, those anecdotes went largely ignored. And therein lies the danger.
When anecdotes start recurring, it is wise to start paying attention. A short dose of antibiotics is one thing, but if clinicians are not aware of the neurotoxic effect of some antibiotics, there is the serious risk that a patient taking these drugs over an extended period of time may be misdiagnosed, and labelled with a psychiatric disorder.
“While diarrhoea is a commonly associated adverse effect of many antibiotics, toxic effects on the central nervous system are perhaps much less recognized.” (Grill & Maganti, 2011)
Neurotoxicity is described as a common effect among many groups of antibiotics. Some penicillins in particular are implicated in behavioural changes, progressive confusion and seizures. The quinolones are associated with seizures, confusion and psychosis.
The reason for these psychiatric side effects lies in the altered composition of the gut microbiota. Microbiota is the collective term for all the microbes living in the gut.
In the early 20th century — a hundred years ago — probiotics containing strains of the Lactobacillus bacteria were advertised in medical journals as a treatment for psychiatric disorders.
A probiotic is a supplement containing “friendly” bacteria — the opposite of an antibiotic. There’s your second clue.
This oral “bacteriotherapy” was a regular treatment for mental ill health and was quite heavily marketed, but without any evidence to support the unregulated and often wildly exaggerated claims that embellished advertisements.
The scientific community was uneasy with some of the promotional overkill, including assurances such as “Not only a banishing of mental and physical depression, but a flooding of new vitality throughout the system”.
The sceptics won the argument, eventually. And that was the end of that passing fad.
The marketers shot themselves in the foot, because there was more than a nugget of truth buried in all the hype. Happily, truth will out, and that nugget has now been unearthed, with the return to mainstream medicine of probiotic therapy — this time with the evidence.
Brains and bowels
One of the most exciting recent developments in modern medicine is fecal microbiota transplant (FMT). Actually, as you might guess, it’s not all that new. The first recorded use is in 4th century China.
FMT is exactly what you’re thinking it is. Fecal matter is collected from a healthy donor (it’s ok; it’s screened) and implanted into the colon of the recipient, via the most obvious direct route. This simple technique has been found to be highly effective in the treatment of antibiotic-resistant infection caused by Clostridium difficile, or C. diff.
This gastrointestinal infection is frequently the result of antibiotic therapy that has killed off the friendly bacteria, leaving the host vulnerable to colonization of hostile, life-threatening pathogens. C.diff. can cause fatal diarrhoea, and more and more people are dying from the disease.
The success rate for FMT as treatment for recurrent C. diff. is estimated to be well over 90%. The psychological appeal of the treatment is estimated to be about 0%; it’s a process that lends itself alarmingly well to visualization. But setting aside any emotive response, the fact is that FMT is highly effective, cheap and safe. No single serious side effect has ever been reported. For that reason, more and more physicians in the United States are performing FMT.
If bacterial therapy can eliminate C.diff., there is exciting potential for other matters of health. That thought has already occurred to scientists working in other fields, including mental health.
“Probiotic administration (e.g. Lactobacillus) and fecal microbiota transfer for conditions associated with depression and anxiety is not a new concept.” (Bested et al, 2013)
When you take antibiotics, you effectively destroy the good with the bad. The “friendly” bacteria that live in your gut are carpet-bombed, along with everything else.
You need good bacteria, not only to maintain your digestive and immune health, but also your mental health.
FMT is essentially about repopulating the gut with the friendly bacteria that are able to wipe out the C.diff. bacteria. Fortunately, when it comes to improving mental health, another route is possible: oral administration of bacteria in capsule form, which does not require a donor.
Interest in probiotics as a treatment for depression was first proposed (second time around) in a paper published in 2005 in the journal Medical Hypotheses.
“Since then there has been an accumulation of data from both clinical and preclinical studies supporting the view that probiotics may have a role in the treatment of depression” (Bested et al, 2013)
Professors John Cryan and Ted Dinan are co authors (with Scott C Anderson) of the book The Psychobiotic Revolution, which was published this year (2018).
For the last 13 years Cryan and Dinan, from the University College Cork, have been researching the gut brain connection, and how our gut microbiota can influence our brains. According to Dinan:
“We have shown that people who are clinically depressed have less diversity in the bacteria in their gut than people who are not depressed. The question now is how can we improve the diversity of our bacteria.”
Of Mice and Men
Changing the composition of microbes in the gut can affect emotional behaviour. This phenomenon was first seen in animal models of depression.
When germ-free mice are reared in a sterile environment, normal brain function is negatively affected, and they show heightened stress and anxiety responses, together with “dramatic” changes in serotonin transmission.
Lack of the “happy” neurotransmitter serotonin is associated with depression.
When healthy bacteria are introduced into their guts, the mice show notably decreased anxiety.
The two strains of bacteria shown to have these positive effects are the Bifidobacteria and the Lactobacillus — strains also found in the healthy human gut.
In humans, the research is still at the early stages. But it is promising: in one double-blind, placebo-controlled study, healthy subjects were given either a mix of probiotics or a placebo, for 30 days. Neither group knew which treatment they had been given. Using various questionnaires designed to assess levels of stress, depression and anxiety, those given probiotics demonstrated “significantly less psychological distress” than those taking the placebo.
How it works: the brains in your belly
Those gut feelings are not all in your head; they really are in your gut. It’s weird and a little otherworldly.
If you have ever thought that your innards appear to have a mind of their own, it’s because they do. Deep within your abdomen is a brain which works semi-independently of the one in your head.
Technically known as the enteric nervous system, the gut-brain consists of a network of over 100 million neurons lining the digestive tract. Interacting with those neurons are approximately 100 trillion microbes, creating a weight of around 4lb. There are approximately ten times as many bacteria as cells in the human body.
The gut environment is a parallel universe teeming with life and death. Bacteria, transients, opportunists and freeloaders all merrily coexist along the tube that runs from your mouth to your anus. It’s like dining at The Restaurant at the End of the Universe.
The gut brain is connected to the head brain via the vagus nerve, the longest nerve in the body’s autonomic nervous system. Think of the vagus nerve as a two-way superhighway, along which messages are exchanged. This superhighway is often referred to as the gut-brain axis.
The bacteria in your gut can profoundly influence brain chemistry. They produce neurotransmitters, chemical messengers that enable communication between neurons. Some of these neurotransmitters are involved in mood regulation. One in particular — serotonin — plays an especially important role.
It may seem far-fetched to suggest that gut bacteria can control your mood, but it’s not so weird when you consider that about 95% of the body’s serotonin is found within the digestive tract.
Commonly prescribed antidepressants — selective serotonin reuptake inhibitors (SSRIs) — work by maintaining serotonin in the brain.
In the past, researchers did not believe that the serotonin in the gut affected the brain, which has its own serotonin supply. But over the last decade or so, there has been a flurry of research activity, all suggesting otherwise.
Beyond depression — from autism to dementia
It stands to reason that if gut bacteria influence the mind and can cause depression, they might also trigger other neurological disorders.
Their influence begins at birth and is lifelong. The microbiota is determined by many factors, including birth method, feeding, diets, and of course use of antibiotics.
Prior to birth, the fetal gut is sterile. In vaginal births, the baby’s gut is primarily colonised by Bifidobacteria, Lactobacilli, and Bacteroides. Caesarian born babies have a microbiota similar to that of their mothers’ skin.
It has long been suspected that autism is related to altered gut microbiota. Multiple trials have found gut abnormalities in children with autism spectrum disorder (ASD) compared with children without the condition.
“It has been found that a majority of children with ASD display gastrointestinal symptoms” (van De Sande et al, 2014)
One study suggested that 70% of children with ASD have a history of gut complaints. Onset of the disease often follows antibiotic treatment, often for the treatment of ear infections.
As you get older, moving from middle-age to old-age, your gut bacteria change. These changes, which involve decreased diversity and stability, can cause problems for older folk.
The situation is not helped by the fact that the use of antibiotics is rife among elderly people in hospital and in care homes. The effect, as we have seen, is vulnerability to overgrowth of dangerous bacteria, including C.difficile.
The damage is not limited to life-threatening infection, though that would be bad enough.
There is also an association with dementia. In trials, sterile mice experience memory problems and other cognitive difficulties, a situation that is partially reversed by probiotic therapy.
In humans, it is not entirely clearly how disruptions to the gut microbiota might be linked to dementia, but it is thought that inflammation is the driver. Pathogenic microbes create substances called amyloids, which clump together forming plaques. Amyloid plaques are toxic to the brain and are a feature of the brains of people with Alzheimer’s disease.
“Dysbiosis and alterations of the gut microbiome composition have been shown to contribute to the development of several diseases in humans, such as inflammatory bowel disease, type 2 diabetes, metabolic syndrome, obesity, allergies, colorectal cancer, and Alzheimer disease” (Pistollato et al, 2016)
Feed and grow your friendly gut bacteria
You probably don’t need a fecal transplant, and you may not even need to take probiotics. You can increase the levels of friendly bacteria in your gut, and encourage their growth, through diet. See my article How gut bacteria can lift depression. Be sure to feed them well for further details.
Bacteria: Back to the future
These discoveries open up exciting new possibilities for treatments for mental health problems, not to mention intestinal disorders.
“The initial skepticism about reports suggesting a profound role of an intact gut microbiota in shaping brain neurochemistry and emotional behavior has given way to an unprecedented paradigm shift in the conceptualization of many psychiatric and neurological diseases.” (Mayer et al, 2014)
Antibiotics were introduced in the 1930s, following the discovery of penicillin by Sir Alexander Fleming. They revolutionised modern medicine, and meant that death from bacterial infection was no longer inevitable.
But we should have known better than to think we could outwit microscopic life. Bacteria are present everywhere on the planet and in the Earth’s crust. They don’t even mind living on radioactive waste, so a few antibiotics pose no challenge whatsoever to their omnipotence.
The resurgence of interest in probiotic therapy could not be more timely. The disaster that is antibiotic resistance is galloping directly towards us, overtaking the Four Horsemen of the Apocalypse along the way. Described by the World Health Organization as “One of the biggest threats to global health”, the overuse and misuse of antibiotics has resulted in bacteria mutating into bigger, stronger versions of themselves, resistant to antibiotics. Infections such as pneumonia and tuberculosis are becoming harder to treat, as antibiotics weaken and fade.
As they lose their effect, they make space for pathogens to damage brain function.
“Alteration of brain function may therefore add to the many reasons that inappropriate antibiotic use should be avoided.” (Rogers et al, 2016)
As this particular disaster unfolds, so too does another. We are in the middle of a global epidemic of mental ill-health. The World Health Organization describes depression as the leading cause of disability worldwide. Consider also that:
- In children in the UK severe mental health prevalence continues to rise: 7.9% in 2000, 8.5% in 2007 and 9.3% in 2014. (Mental Health Foundation).
- In the 1980s, 1 in 10,000 people in the US had ASD. In 2012 that figure was 1 in 88. In 2016 it was 1 in 68.
- It is estimated that the number of people across the globe living with dementia is 46.8 million, and this figure is predicted to double by 2030.(Mental Health Foundation)
- Dementia is now the 6th leading cause of death in the US. (Alzheimer’s Association)
It is time to start joining up the dots here. One reason for the current, global crisis in mental health may be the unsustainable, global crisis that is antibiotic resistance. The answer to both crises may lie in your bowels.
“The next few years of research hold the potential of uncovering intriguing connections between gut bacteria and neurological conditions that may possibly impact human health.” (Mayer et al, 2014)
Bacteria are the glimmer of hope rising from Pandora’s Box. They may well be the medicine of the future.
It’s all about cunning strategy. Sometimes the best way to overcome adversity is to make more friends, not try to destroy your enemies. Such an attack would be futile: bacteria were here long before we made our way down the evolutionary chute, and will still be here long after we are gone.