In my clinical practice, countless people are tormented by the stresses around them. As doctors, we tell our patients to have a healthy diet if their cholesterol is high or has high blood sugar. But when somebody walks through the clinic doctor presenting with low mood, a healthy diet is never emphasised to the extent of the other physical health conditions such as diabetes.
All this may be changing.
Our gut is one of the most important organs in the body. Over the last few years, it has been increasingly clear that a healthy gut is not just good for absorption of nutrients, it is also having a surprisingly enormous impact on our mental health.
The gut is a unique organ because it has its own neural network called the enteric plexus. Enteric means gut. Plexus means a small network of interconnecting neurons. Enteric plexus acts as a mini-brain, in the sense that it has its own network of neurons without direct relations with the brain. However, it does connect with the brain via a variety of mechanisms. The connection between the gut and the brain is the gut-brain-axis.
Regulation of the gut-brain-axis function is associated with changes in the stress response and overall behaviour in both animal models and in humans <1>. Irritable bowel syndrome (IBS), a common stress-related gut problem is an excellent example of how the health of the gut may be influencing the functioning of the brain and vice versa. Over half of patients with IBS also suffer from anxiety or depression.
What, then, maintains the health of the gut?
We all know there are good bacteria living in the gut. It is old knowledge that digestion is closely regulated by the health of the good resident bacteria in the gut, the so-called microbiota. The new knowledge is the crucial roles a healthy microbiota plays on the rest of the body, outside the digestive system.
Gut microbiota is not just regulating the health of the gut but are also involved in the manufacturing of several important brain chemicals, the neurotransmitters, which are essential components of efficient brain functioning. Moreover, the microbiota interacts with the host through a variety of pathways involving the immune molecules, hormones and the nerve connections, as part of the brain-gut-microbiota axis<1>. Animal studies have demonstrated evidence which suggest that they are actively involved in the regulation of brain development, function and behaviour.
What is the evidence for the link between gut microbiota and mental health?
In recent years, there have been some very interesting new animal studies which put gut microbiota in the spotlight of the field of mental health and neuroscience. Preliminary studies have shown that the composition of gut microbiota is different in people with depression, compared to that in healthy people without depression<1>. They literally have different types of bacteria. How does this translate in clinic research? Perhaps you have heard of faecal transplantation. This is a clinical treatment essentially involving harvesting a healthy volunteer’s poo and put it in a patient’s gut, in the hope that the good bacteria in the donor poo will populate the gut of the patient, restoring the healthy gut microbiota in the patient. This is no longer a novel treatment and is currently being used to in the treatment of certain gut disorders. It is yet to be applied to treat mental health disorders such as depression but as you will see in the studies described below, this method may help us elucidate the relationship between gut microbiota and mental health.
So far, majority of the studies have been done in mice<1>. Genetically modified mice that were born without any bacteria in their gut, so-called germ-free mice, underwent transplantation of faeces pooled from several humans with depression. As a result, they developed what could be perceived as ‘depressive behaviour’, such as reduced swimming activity when put in a pool of water. On the other hand, the behaviours of germ-free mice were unchanged after they had faecal transplantation from healthy people. In another older study, germ-free mice have been found to have an overactive stress response. This hyper-response was reverse by introduction of Bifidobacterium infantis, bacteria normally found in infant gut and commonly used in probiotics<2>.
Some critics may argue, what if germ-free mice are just more susceptible to the germs unknown to them? Well, that is certainly a valid point. In fact, it was found that germ-free mice do have abnormal development of the brain and immune system<1>. This supports the hypothesis that gut microbiota is involved in regulation of the brain development and immune system maturation. Luckily, this issue with the germ-free mice was addressed in another study by using adult mice that were developed normally but had their gut microbiota stripped in adult life. This eliminated the confounding factor of possible abnormal brain development. Guess what, these mice also developed characteristics of ‘depression’, after receiving the faeces transplant from depressed patients<1>.
You may ask, can we improve the mood of these ‘depressed’ mice by improving their gut microbiota? One study has done just that<3>. It found that the ingestion of a bacteria, called Lactobacillus rhamnosus, reduced anxiety and despair-like behaviour and reduced the stress hormones in mice. This finding begs the question: can our anxiety and depression also be alleviated by ingesting such bacteria?
What could we conclude from these studies?
As a scientist, I’m sorry to say that despite the interesting findings these studies have shown, they do not in any way prove that gut microbiota regulates mood. Mice are obviously not humans. How these findings can be translated into humans is still questionable. There are many questions that are still unanswered. Does depression lead to change in gut microbiota? Or perhaps it is the other way around? Is it a chicken and egg thing? We don’t know yet. However, our doors of curiosity are certainly wide open.
Now comes the most relevant question: what can we do to improve the health of gut microbiota?
In investment, diversification is key. In gut microbiota, diversification is key. A healthy diet is certainly the most important step to increase the biodiversity of gut microbiota. You may have heard of the term prebiotic and probiotic. Prebiotics are compounds in food that induce the growth of good bacteria. These are foods such as leeks, artichokes, onion and garlic. Sounds healthy right?
If eating plenty of prebiotic-rich foods are difficult for you, perhaps you could consider a reasonable intake of probiotic. Probiotics are live bacteria that help restore the diversification and health of gut microbiota. However, just be aware that in very rare cases, some people may develop intolerance to probiotics.
So, what is the verdict?
A healthy diet can certainly improve the health of gut microbiota. Can healthy gut improve our mood? Maybe. Animal studies have been promising so far, but let’s watch this space.
<1> Dinan et al. Brain-gut-microbiota axis - mood, metabolism and behaviour. Nature Reviews Gastroenterology & Hepatology 14, 69-70 (2017)
<2> Sudo, N. et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J. Physiol. 558, 263–275 (2004).
<3> Cryan et al. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience 13, 701-712 (2012)