As I discussed in last week’s blog post, Drugs and gut bugs, research on the human gut microbiome is burgeoning at an astonishing rate. One of the most fascinating areas of research is the complex interplay between our bugs and our brains – the constant back-and-forth signalling between our gut microbiota and regions in our brains that process emotions, mood states, the flashes of inner knowing that we call ‘gut feelings’, and even our preferences for the company of certain people and the taste of certain foods.
For some time, researchers have investigated ‘the gut–brain axis’:
“a bidirectional communication network that monitors and integrates gut functions and link them to cognitive and emotional centres of the brain.”
However,
“Given mounting evidence that the microbiome has a key role in influencing the development and function of the nervous system through its interaction with the gut–brain axis, it has been suggested that a ‘microbiome–gut–brain axis’ may be a more appropriate model.”
Our growing understanding of this ongoing conversation between our brains and our gut microbiota holds enormous promise for developing new approaches to common psychological problems such as anxiety and depression that focus on shifting the composition of the gut microbiota in a more favourable direction, through alterations in diet, and possibly supplementation with prebiotics (substances that selectively feed desirable bacteria) and particular probiotic strains of bacteria.
It also validates the experience of hundreds of my clients – and tens of thousands of people all over the world – who have noticed dramatic improvements in their psychological functioning when they adopt a diet that promotes a healthy, diverse gut microbiome; that is, a wholefood plant-based diet.
This improved functioning is reflected in statements that I commonly hear from clients who have slashed or completely eliminated animal products, oils and fatty foods, and refined carbohydrates:
“I just feel better!”
“I feel lighter, somehow.”
“My brain fog has cleared.”
Of course, we also need to be aware of the potential impact of common medical practices on the gut-brain axis. As I discussed in Drugs and gut bugs, nearly one quarter of drugs on the market today have been found to inhibit the growth of at least one strain of bacteria that forms part of our gut microbiota.The impact of such disruptions to the complex ecosystem of the gut has simply not been studied at this stage.
What is known, however, is that certain antibiotics, which exert major effects on the gut microbiome, can affect psychological functioning in profound ways, including:
1. Antibiotic-induced psychosis
Psychosis is a mental disorder in which a person loses the ability to distinguish what’s real from what isn’t. During a psychotic episode, a person may experience hallucinations (seeing or hearing things that aren’t there) and delusions (believing things that aren’t true), as well as confused or slowed thinking.
There are many case reports of antibiotic-induced psychosis in the medical literature. A 2014 systematic review of case reports of antibiotic-associated psychosis during treatment of urinary tract infections found that 3 different classes of antibiotics – fluoroquinolones, penicillins, and trimethoprim-sulfamethoxazole – had been reported to trigger psychosis within 1 week of commencing treatment. After ceasing the antibiotic, the psychosis resolved, again within a week. In some cases, doctors ‘rechallenged’ by administering the antibiotic again to patients after they had recovered from psychosis, and they relapsed back into psychosis.
One mechanism that has been proposed to explain antibiotic-induced psychosis is a sharp drop in levels of d-alanine, an amino acid that is produced by gut bacteria (as well as being supplied by the diet). Alanine binds to N-methyl-D-aspartate (NMDA) receptors in the brain. Underfunction of these receptors has previously been linked to symptoms of schizophrenia, which is a form of psychotic disorder; and drugs that block the activity of NMDA receptors, including ketamine and phencyclidine, are known to be capable of inducing psychosis.
According to this theory, antibiotic-induced psychosis is triggered when antibiotics cause depletion of d-alanine-producing intestinal flora, resulting in less d-alanine in the brain, and hence reduced stimulation of NMDA receptors.
Another potential contributing factor to antibiotic-induced psychosis is inflammation induced by the dysbiosis (imbalance in gut bacteria) that results from antibiotic treatment.
Antibiotic treatment is known to favour the proliferation of the Bacteroides family of bacteria, which harbour many antibiotic resistance genes and therefore tend to become dominant when antibiotics wipe out less resistant members of our gut microbial community – including beneficial species such as Lactobacilli, Bifidobacteria, Akkermansia and Faecalibacteria.
Bacteroides, along with other gram negative bacteria, secrete pro-inflammatory neurotoxins including a substance known as surface lipopolysaccharide (LPS), which triggers an inflammatory response by our immune system. Many studies have reported higher inflammatory markers in schizophrenia patients as well as lipopolysaccharide binding protein, which is produced by the immune system to neutralise LPS, in people with schizophrenia.
2. Antibiotic-induced anxiety and panic
A large population study conducted in the UK found that a single course of antibiotics raised the risk of developing anxiety, with risk rising higher with each course of antibiotics. Penicillins and sulfonamides were the biggest culprits; a single course of penicillin was associated with a 17% higher odds of developing anxiety, while people who had taken more than 5 courses of penicillin had 44% higher odds of anxiety.
Antifungal drugs were also found to increase the risk of anxiety, but their effect was less pronounced than antibiotics.
3. Antibiotic-induced major depression
The same UK study found that the risk of depression was also increased by a single course of any type of antibiotic. Penicillin was found to raise the odds by 23%, and quinolones by 25%. As with anxiety, the risk increased with each subsequent round of antibiotic treatment: 2-5 courses of penicillin led to 40% higher odds of developing depression, and more than 5 courses raised the odds by 56%.
Again, as with anxiety, antifungal drugs slightly raised the risk of developing depression.
As with psychosis, one mechanism by which antibiotics cause depression may involve LPS, which is overproduced as a consequence of antibiotic-induced dysbiosis. Our immune systems respond to the presence of LPS by producing antibodies. Levels of serum antibodies against lipopolysaccharide have been found to be higher in patients suffering from major depressive disorder (MDD) than in non-depressed people.
Given the well-documented role that antibiotics play in inducing both common psychological problems and severe mental disorders, and the increasing prevalence of these issues – including in children and adolescents – doctors need to be much more discerning in their prescription habits, and members of the public must become better informed about the risks of antibiotics.
Some examples:
- Most cases of childhood middle ear infections do not require antibiotics, but parents still tend to pressure doctors to prescribe them, and unfortunately many doctors continue to do so (with or without parental pressure) even when they know there is little chance of the child benefiting from antibiotic treatment, as well as a significant risk of harm.
- Antibiotics should not be routinely prescribed for sinus infections, as the harms clearly outweigh the benefits. A Cochrane review concluded that conclude that “there is no place for antibiotics for the patient with clinically diagnosed, uncomplicated acute rhinosinusitis”. They found that “only five more participants per 100 will cure faster at any time point between 7 and 14 days if they receive antibiotics instead of placebo” but 27% of the participants who received antibiotics experienced adverse events vs 15% of those who received placebo.
- Between 25 and 42% of uncomplicated urinary tract infections (UTIs) in women resolve spontaneously, without any treatment at all. For women at low risk of complications of a UTI, home remedies accompanied by watchful waiting for signs of complications (which include increased frequency and urgency of urination, pain or burning when urinating, low grade fever, pressure or cramping in the lower abdomen and groin, cloudy, murky, or bloody urine, and a change in the odour or urine) is a viable option to avoid both the risks of adverse reactions to antibiotics, and the development of antibiotic-resistant strains of bacteria which may render antibiotics useless when they are truly needed.
As a health practitioner, I’m seeing an increasing number of clients, from childhood upward, who suffer from psychological difficulties – especially anxiety and depression. All of them have a history of insults to their gut microbiome, with overuse of antibiotics featuring in many of their medical histories.
It takes a lot of work to restore a damaged gut microbiome to health. Although most people respond well to dietary change, exercise, stress reduction, prebiotics, and targeted probiotics, in some cases, it may not be possible to fully rehabilitate the gut.
The bottom line is that we need to see ourselves as custodians of our gut microbiome – and health and medical practitioners need to see themselves as custodians of their patients’ or clients’ gut microbiomes. Hippocrates’ maxim, “Firstly, do no harm” has never been more relevant than today, as both our understanding of the importance of the teeming communities of bacteria that inhabit our bodies, including our guts, increases, and the number of treatments that can harmfully alter those communities expands.
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