The Psychobiotic Revolution: an inspiration for discovery.
Whenever a new book claims a new health revolution, I must admit I am a little sceptical. Nevertheless, the notion that the bugs in our intestines can influence our gut health, but also our mood and the way our brain works, is as old as the hills as well as being cutting edge science. Written by science journalist, Scott C. Anderson, together with research scientists John Cryan and Ted Dinan from the University of Cork, The Psychobiotic Revolution, is packed with fascinating insights and new ideas that might well revolutionise the way we think about our food and our mood.
But psychobiotics are not new. As early as 1909, Dr Hubert Norman reported the use of soured milk in treating melancholia and the following year, Dr George Porter Phillips published his treatise on ’The treatment of melancholia by the lactic acid bacillus’. The Nobel laureate, Dr Elie Metchnikoff, already renowned for his discovery of macrophages, had also reported how some Bulgarian peasants survived to a great age on a diet that included generous amounts of fermented milk, somewhat akin to kefir, though there was a lurking suspicion that the men, who were the subjects of that observation, may have falsified their age to avoid conscription.
Whatever goes round, comes round. So in the last few years, scientists have demonstrated that depletion or instability of the colonic or faecal microbiome (dysbiosis) may be accompanied by anxiety and depression. Dysbiosis is common in western societies and frequently associated with an unhealthy life style. Obesity, lack of exercise, junk food, stress and alcohol can all deplete or destabilise the colonic microbiome and are often associated with anxiety and depression. High sugar/fat comfort food may briefly raise mood, but people soon become tolerant and eat more, contributing to a vicious cycle of dysbiosis, anxiety and obesity.
Teenage is often a time of psychobiological dysregulation, when sleep deprivation, poor eating habits and frequent courses of antibiotics can deplete and destabilise the microbiome. This might explain why so much IBS starts in teenage or shortly afterwards.
The inference from this book is that microbial depletion, induced by diet, stress or antibiotics, may cause low grade inflammation not just in the gut but also in other organs, which might explain associations between IBS, other illnesses and general dysphoria. Association, however, does not necessarily imply causation.
Links between dysbiosis and mood change.
It cannot just be coincidence that the bacteria in our colons produce the same neurotransmitters that influence mood and behaviour in our brains. They include serotonin, dopamine, gamma amino butyric acid (GABA) and acetylcholine. Serotonin is responsible for feelings of well being, dopamine is part of the brains reward system and GABA is a tranquilliser. Bifidobacteria, a keystone genus in the gut and a component of many probiotics, can also release butyrate which nourishes colonic epithelial cells, suppresses inflammation, reduces depression and stimulates ‘brain derived neurotrophic factor’ (BDNF), the brain’s growth hormone which aids memory and learning. Some lactobacillus species can even manipulate opioid and cannabinoid receptors in the brain. Finally both bifidobacteria and lactobacilli spp can produce B vitamins, a shortage of which may lead to depression.
How most of these transmitters gain access to the brain is not entirely clear, since the healthy blood brain barrier normally inhibits the transfer of all but glucose, butyrate, amino acids, some small peptides and lipid soluble substances into the extracellular fluid that bathes the brain. Perhaps they get through via the circum-ventricular organs, such as the area postrema, pineal gland, hypothalamus and median eminence, where the blood brain barrier is more permeable and there is a direct link between blood chemistry and autonomic nerve function. Or maybe they get into the brain by axonal transport along the vagal nerve. Inoculates of bifidobacteria in the colon can reduce anxious behaviour in rodents, but this is reversed if the vagus is cut.
Depletion of the microbiome can increase gut permeability and release cytokines from the epithelial cells lining the colon and immune cells. These can result in low grade inflammation throughout the body including the brain. Injection of cytokines causes sickness behaviour in rats and, when used as therapy for cancer or viral infections, can induce depression in humans. There is evidence that the latter may be mediated by suppression of serotonin and may act via the vagus nerve, the circum-ventricular organs, or directly compromise the integrity of the blood brain barrier and activate microglia, the brain’s immune cells.
Timid Mice and Depressed Rats
The earliest studies documenting the effect of the microbiome on behaviour were conducted on germ free mice. Germ free mice have abnormal neurochemistry in the amygdala, the alarm bell in our brain, and an exaggerated response to stress. This suggests that the microbiota might be regulating the growth of important memory and emotionally reactive centres in the brain. Inoculating the gut with faeces from other mice can transfer timid or exploratory behaviour. Similar results have been observed between species. Rats that received faecal matter from depressed patients showed signs of ‘depression’, whereas mice that received faecal inoculates from IBS patients, developed ‘anxious behaviour’.
These studies raise questions about how investigators might recognise depression or anxiety in experimental animals. In Chapter 6, Anderson asserts that, stripped to its essentials, depression is almost indistinguishable from sickness behaviour. If that is so, does the epidemic of depression throughout the western world mean we are more sick? And do the things that happen in our everyday lives make us ill or is it all due to the effect of our diet on our microbiome? It is a big jump from experimental observations in mice to illness in humans and with no biological marker for depression or illness behaviour, such studies are difficult to interpret.
Psychobiotics
Cultures of certain beneficial colonic bacteria can alleviate depression and psychosis in humans. Several species of Bifidobacteria, for example, can calm distress and reduce the release of inflammatory cytokines in patients with IBS.
Similarly prebiotics, food ingredients that encourage the growth of beneficial bacteria, can also affect mood. Fructo-oligosaccharides (FOS) and Galacto-oligosaccharides (GOS), the small chains of sugars found in vegetables, cereals and pulses, counter the immune and behavioural changes found in stressed mice. Moreover a commercially produced GOS, called Bimuno, increased populations of Bifidobacteria and improved depression and anxiety scores as well as gut symptoms in human subjects with IBS.
Food; the best psychobiotic.
Anderson and his colleagues claim that foods are the best psychobiotics. These not only include yoghurts or kefir, but also fruits and vegetables, in which bacteria may be actually growing on the plant parenchyma, and bean ferments such as soy, dark chocolate and coffee. Colonic fermentation also liberates B vitamins, which reduce depression. In an adaptation of the traditional dietary pyramid, he advocates a psychobiotics food pyramid: grains, vegetables and fruit with each meal; seeds, nuts, herbs,essential oils and fermented products daily; fish and seafood, poultry and eggs two to five times a week and sweets and red meal once a week or less.
If you have IBS, it will not have escaped your notice is that the foods that are so good for building a healthy microbiome and preventing inflammation and illness, including anxiety and depression, contain large amounts of FOS and GOS. These are major components of FODMAPs, which exacerbate symptoms of bloating, abdominal pain and bowel disturbance in people with a sensitive gut.
Diets low in FODMAPs are currently all the rage because they reduce gas formation and fluid retention and so suppress IBS symptoms from a sensitive gut. Nevertheless low FODMAP diets also reduce deplete populations of beneficial bifidobacteria. This suggests that while they improve IBS symptoms in the short term, they may maintain a state of sensitivity that undermines mood and recovery in the longer term. In other words a low FODMAP diet may win the battle against the symptoms, but lose the war! Advocates of the low FODMAP diet rightly advise that it is not for life, but they might suggest it is not even for the medium to long term. Patients could be advised to control their symptoms with a simplified low FODMAP diet (reducing pulses, onions, stone fruits and bread) while implementing other changes to restore the microbiome and reduce the sensitivity and inflammation. These may include adding polysaccharides (soluble fibre) and plant foods that are slowly fermented and omega 3 fatty acids, reducing sugar and alcohol, adopting regular exercise, which releases anti-inflammatory chemicals that damp down the immune system, and reducing stress. Andersen even suggests that talking therapies might be regarded as a conversation between the therapist and the gut microbiota.
Conclusion
The Psychobiotics Revolution outlines the recent discoveries concerning the complex interactions between what goes on inside our guts and the way we feel. It is packed full of intriguing possibilities, but, as with the whole area of probiotics, it has to be said that the jury is still out. The hypothesis that dysbiosis adversely affects mood is plausible and interesting and may well yield more targeted and effective treatments for mood disorders, but at yet, there is insufficient data.
Much of the evidence is based on animal studies, where effects on mood can only inferred from studies of behaviour, awaiting substantiation by observations in humans. But mood is difficult to study even in human beings. There is no acceptable biological marker and results from questionnaires it cannot fail but be influenced by belief and expectation. Maybe that doesn’t matter. As research findings accumulate, they may well encourage more people to adopt life styles that create a diverse and stable microbiome. The outcomes of this in terms of health can then be tested against populations that have remained on what is currently a standard diet of highly processed foods.
I have enjoyed reading ‘The Psychobiotics Revolution’; it is full of fascinating ideas that generate all kinds of questions. Where do our moods originate from? Is anxiety related to hunger and might it be caused by inhibition of the release of feel-good chemicals by colonic micro-organisms deprived of energy and essential nutrients? Is depression a stage on from that, caused by the inflammatory cytokine response to microbial depletion? And what about our intuition? Has the notion of gut feelings been correct all along; the unconscious memories of the effect of previous situations on our microbiome, translated into action by our emotional brain? And what about faecal microbial transplants? Can we envisage a future where faecal suspensions from happy people might be used to treat depression? Surely not!
Such is the stuff of science fiction; the engine of imagination, which drives discovery. Watch this space!
The Sensitive Gut 