Anorexia and our second brain.

Originally published in 'The Oxford Scientist'

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Originally published in 'The Oxford Scientist' -

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric disorders. As someone with experience of this illness, it is horrifying to see statistics like this. But what is life like for the survivors? Various studies have proven how acutely the microorganisms in our guts respond to illness — AN is no exception.

What is the gut microbiome?

Our digestive tracts, including the intestines and oesophagus, are home to an array of microorganisms. These species interact with our bodies and with one another to form the “gut microbiome”. This system can be beneficial to us, for example by breaking down food that we would otherwise be unable to process. Imbalances in the microbiome (known as dysbiosis), however, can be created by sources of stress — in some cases, infection has been shown to lead to permanent alterations.

The link between the brain and the gut (the “gut-brain axis”) has been discussed prolifically over recent years. The concept suggests that our diet influences our emotions, clarity of thought, and even our behaviour. It also highlights the influence that our gut microbiome can have on different disease states, such as Alzheimer’s disease and eating disorders.

The connection primarily surfaces from the production of small molecules called neurotransmitters by gut microbiota. These molecules are received by the brain, where they stimulate a response, such as hormone release or mood change. In AN, reception of these molecules by the brain is impaired, with particular effects noted in the connection of the hypothalamus to other brain regions. This area of the brain is responsible for maintaining balance between all processes in the body. Therefore, in the clutch of AN patients are subject to chaotic moods and fever-like temperature changes, amongst other symptoms. Further effects of a damaged axis are the aberrant levels of ghrelin and leptin: neurotransmitters that control feelings of hunger and satiety, respectively. There is thought that one could just “snap out” of AN to make new and “better” choices. When both our mind and body are working against us, it is not that simple.

How does the gut microbiome impact AN?

We have limited knowledge on the root causes of AN. While there is a significant social factor, including exposure to certain media and body-shaming, researchers have suggested that there is a metabolic basis to the disorder, concentrating around the gut microbiome. Here, an altering composition of the gut in response to starvation and stress has a “cycling” effect, in which the resulting bacterial activity perpetuates and causes certain AN characteristics. These include constipation, psychiatric symptoms like depression, and chronic inflammation.

It is still yet to be confirmed whether a changing microbiome is a cause or effect of AN. Nevertheless, scientists have performed experiments involving DNA and protein sequencing technology to try and recapitulate AN pathophysiology. Indeed, female AN patients show gut microbiota alterations, with significant trends in certain bacterial subtypes. An increased amount of methane-generating (methanogenic) bacteria, for example, is seen in AN cases. These species survive by fermentation — a process by which organisms use carbohydrates to produce energy in the absence of oxygen. Notably, they can survive even when a carbohydrate source is lacking. This is key to why their numbers increase in the guts of AN patients: low carbohydrate intake has a compounding effect. "Good” gut species lose a fuel source, causing their numbers to wane. Meanwhile, bacteria that can survive in low nutrient conditions begin to thrive in the absence of adequate competition from the species that protect our health. Notably, methane in the gut reduces uptake of essential nutrients such as Vitamin B12.

Interestingly, certain species correlate with particular AN characteristics — for example, elevated levels of Parasutterellabacteria may correlate positively with body dissatisfaction. Moreover, it has been shown that the microbes of healthy individuals, when subject to certain changes in their DNA, become AN-supporting, promoting self-denial, insomnia, and irritability. While it is yet to be discerned what causes these mutations in the first place, pursuit of this research could prove revolutionary for AN patients around the world.

What are the long-term effects of AN?

So far, we have discussed the microbial shifts that occur during AN and, by extension, how these shifts reinforce its symptoms. Nevertheless, these effects are not confined to the course of the illness. Significantly, ‘dysbiosis might persist beyond weight recovery and potentially contribute to relapse. Research suggests that the changes in the gut microbiome of AN patients correlate with the development of other conditions. For example, many experience symptoms of Irritable bowel syndrome (IBS). This gut inflammatory disorder is linked to the deregulation of our gut microbiome and has direct links to depression. Furthermore, increased diversity in the species seen in the guts of AN patients is correlated with an increased risk of complications during pregnancy. As someone who would love to be a mother, this prospect is terrifying, and it is not fair or right for survivors to blame themselves for their AN-linked health complications. Currently, researchers are investigating whether we can help survivors to recover their gut microbiome, reducing these later life risks.

“Mimicking” healthy gut microbiomes

For all the discussion of typical alterations seen in AN, there is a practical application. It has been suggested that faecal microbiota transplantation (FMT) from healthy individuals may aid in the recovery of the digestive tract in AN patients. Indeed, in a germ-free mouse model, an opposing transplant (in which mice received AN faecal matter) caused profound weight loss and subsequent difficulties to regain this weight. This practice, in which the gut microbiome of AN patients is made to mimic those that are healthy, may therefore aid the weight restoration process, which is a key part of recovery.

FMTs have had promising results in clinical trials. Gastrointestinal symptoms in patients improved. In addition, therapeutic transplants may also have a profound impact on the long-term mental effects of AN by removing the species which are implicated in anxiety and/or depressive symptoms. Indeed, trials have shown improvement in the mental state of patients, albeit in small groups.

A less invasive method of mimicry is the taking of dietary supplements, such as pre- and pro-biotics. While a daily practice for some, and generally additive to our gut health, these medications could serve a modulatory role in the re-establishment of a flourishing gut microbiome.

The Future of AN treatments

Classically, AN has been treated with a combination of therapy, medication, and a restorative diet. While helpful for some in the short term, scientists are becoming aware that the long-term effects of AN are being overlooked. Armed with this new information, perhaps microbiome supporting therapies, such as regular probiotic supplements and FMT, could begin to be integrated into the recovery of AN patients.

Of course, there are important hurdles to overcome. Besides needing many more clinical trials in this area, it is important to recognise the variability of AN presentation. While the illness has key characteristics, symptoms can manifest in unique ways, necessitating an individual treatment approach. Studying the mechanisms that underlie the link between AN and the microbiome is essential as we search for further ways to supplement patient recovery.

To summarise, eating disorders affect patients in several and varying ways, but this does not necessarily stop after weight and diet are restored. At present, procedures such as FMT would contribute to recovery in addition to traditional therapy, aiding survivors towards overall happier and healthier lives. Studies into this area, however, are in their infancy — with diagnosed cases of AN on the rise, it is important to raise our voices.