Gut Feeling: The Role of The Gut Microbiome in Anorexia Nervosa
In the last 5 years, hospital admissions for eating disorders have risen by 84%, with over 9,000 admissions for anorexia nervosa between 2020 and 2021. Characterised by excessive weight loss and malnutrition, anorexia nervosa is a complex eating disorder attributed to extreme dietary restriction, distorted body image, and often excessive exercise.
Though a highly debilitating disorder with often fatal outcomes, successful treatment options are somewhat sparse in comparison to other psychiatric conditions. As part of the current treatment, patients tend to undergo a refeed process in which food is reintroduced to encourage monitored weight restoration and re-nourishment. Unfortunately, many patients often experience gastrointestinal distress, including bloating, stomach pain, and constipation, which often resembles symptoms of gastrointestinal disorders. Given that many core features of anorexia nervosa overlap with those in gastrointestinal conditions (including loss of appetite, weight reduction, and altered mood), it may be worth investigating the gut in the hunt for new treatments.
Although never diagnosed with an eating disorder, throughout my teenage years I struggled with restrictive eating and overexercising due to poor body image (why not check out my previous blog on this). Understanding, at the basic level, how difficult a poor relationship with food can be, I wanted to learn more about the potential contributors to eating disorder psychopathology and how, on the back of this, we can help people to recover. So now, as a mental health researcher in the SPI Lab at King’s College London, I thought I would do some digging into this.
Without further ado, let’s get into it!
Gut microbiome and microbial diversity
In our intestines, we have trillions of microscopic organisms, known as microbes or microbiota, that collectively form a diverse community called the gut microbiome. Though our specific collection of microbiota is unique to each of us, the gut microbiome usually contains 5 main microbial species: bacteria, fungi, parasites, viruses, and archaea. However, one progressing line of evidence is that individuals with anorexia nervosa have an imbalance in the expected prevalence of these microbial species in the community (aka microbiota dysbiosis).
So, what does the research say about this microbial imbalance?
As highlighted in a recent review, patients with anorexia nervosa often have an abundance of Methanobrevibacter Smithii (the most dominant methane-producing bacteria in the gut). This has also been reported in patients with irritable bowel syndrome (IBS; a disorder that affects the digestive system, mainly the large intestine), particularly in those experiencing constipation. Considering its methane-producing properties and its role in slowing intestinal transit, it is understandable that Methanobrevibacteri Smithii is associated with constipation and bloating, and that its enrichment could contribute to these complications in patients with anorexia nervosa.
In addition, overrepresentation of this bacteria has also been reported in patients with non-alcoholic fatty liver disease (build-up of fat in the liver) and cirrhosis (scarring of the liver from long-term liver damage). Such association may therefore also translate to instances of liver dysfunction in anorexia nervosa patients.
Comparatively, patients with anorexia nervosa show a decrease in butyrate-producing microbes, such as Roseburia, Ruminococcus, and Clostridium. As a short-chain fatty acid supporting digestive health, butyrate could also be a suspect for gastrointestinal distress in these patients. In a recent study with IBS patients, a 12-week course of treatment with sodium butyrate showed promising improvements for gastrointestinal symptoms including abdominal pain, constipation, and flatulence, suggesting that low butyrate production is associated with gastrointestinal distress. As is the case with Methanobrevibacteri Smithii, there appears to be an overlap in butyrate-producing microbe diversity in patients with IBS and anorexia nervosa; such findings may therefore also explain these gastrointestinal symptoms.
What about psychological symptoms and eating behaviour?
As touched upon in our previous InSPIre the Mind blogs by Viktoriya Nikolova and Lisa Hantso, research indicates a link between altered microbial diversity and poor mental health outcomes, including depression and anxiety. Such conditions are highly prevalent in patients with anorexia nervosa. Indeed, greater levels of depression and anxiety have been associated with reduced microbial diversity in these patients.
Not only this, patients’ microbial compositions have also been associated with disordered eating behaviours and experiences, including dietary restraint and concerns with weight, shape, and eating. Those with lower microbial diversity scored higher across these different aspects. More specifically, as a core feature of anorexia nervosa, dietary restriction may, in fact, be influenced by an abundance of Enterobacteriaceae (a bacteria associated with gut inflammation and infection). As a producer of protein ClpB, a hormone that causes loss of appetite, it is plausible that enriched Enterobacteriaceae in the gut could contribute to poor appetite regulation in patients with anorexia nervosa.
So, how can this be applied to therapeutic intervention?
As mentioned earlier, patients tend to undergo nutritional rehabilitation as part of the current treatment process. This often involves the introduction of a high-fat diet as this macronutrient (a nutrient that we need in large amounts in the diet) is high in calories and thus contributes to quick weight gain. Each macronutrient, however, impacts the gut microbiome differentially, and thus a better understanding of the microbial composition in anorexia nervosa patients may allow us to better tailor their nutritional rehabilitation. This may reduce gastrointestinal-related side effects and improve long-term recovery.
In addition to this, researchers may also be able to screen probiotic supplements(substances that promote the growth of microorganisms with beneficial properties) to find promising interventions that restore microbial imbalances. For example, lactobacilli and bifidobacteria supplementation have been said to increase Roseburia and thus improve butyrate production in both animals and humans. A recent study conducted in adolescent patients with anorexia nervosa showed promising effects of lactobacillus on improving symptoms of constipation over a 6 month period. Though these effects were not evident in the shorter term (across 3 months), findings may suggest probiotics as a complementary therapy to ease gastrointestinal symptoms throughout the recovery process. Probiotic strains that act against ClpB protein producers may also be helpful in eating disorder treatment, perhaps due to the potential role of ClpB in psychobehavioural symptoms. Though the use of probiotics in psychiatric disorders with overlapping psychological symptoms (such as anxiety and depression) is advancing, application to anorexia nervosa is still largely suggestive. A recent trial protocol (a document describing the breakdown of a proposed trial) has proposed to investigate the clinical efficacy of a multistrain probiotic in patients with anorexia nervosa, related to psychological outcomes (i.e. eating-disorder-related psychopathology, depression, and anxiety). Such research, however, is limited.
Nevertheless, the publication of a recent trial in adolescent patients and submission of a protocol aiming to investigate the effects of probiotic use in anorexia nervosa indicates that this field of research is actively trying to use this approach to improve treatment.
Though covering only a few examples, I hope this blog highlights the possible effects of the gut microbiome on eating disorder psychopathology and the start of a potentially promising journey to better treatment for patients struggling with anorexia nervosa.