A recent review, published in Frontiers in Psychiatry, has examined the evidence that the gut microbiome may play a significant role in anorexia.
Anorexia nervosa (AN) is a complex and debilitating eating disorder. It is characterised by a distorted body image and extreme dietary restriction. This is accompanied by severe weight loss and high psychiatric comorbidity. Most importantly, it has the highest mortality rate among all psychiatric disorders. Unfortunately, the development of effective and evidence-based treatments has been hindered by our poor understanding of its aetiology. Nonetheless, it is expected that there is a complex interplay between genetic and environmental factors.
An emerging avenue of research involves the gut microbiome. The gut microbiome is being increasingly acknowledged as a key interface for gene-environment interactions, playing a role in both health and disease. The human gastrointestinal tract is home to an abundant and diverse microbial ecosystem. With ongoing advances in metagenomic sequencing technologies and proteomics, researchers have been able to interrogate these ecosystems. As a result, a growing body of evidence is emerging that points to an association between AN and gut microbiome imbalances.
In this review, researchers from the University of Oxford, evaluated emerging evidence which shed light on the dynamic changes in host-microbiome interactions that may play a role in the course of AN.
Imbalance in AN patients
Several studies have shown that AN patients have microbial alterations when comparing stool samples to participants of normal weight. Nonetheless, results so far have been heterogenous and difficult to interpret. This may be in part due to the differences in methods used to characterise the microbiota. Other studies have shown that lower diversity is significantly associated with depressive symptoms as well as anxiety and eating disorder psychopathology.
Adaptations to starvation
A consistent finding across studies is that AN microbial communities were enriched in Methanobrevibacter Smithii. The abundance of this archaeon was negatively correlated with BMI and may represent an adaptive response to prolonged caloric restriction.
Altered bacterial metabolites
Gut bacteria can also impact host metabolism by the production of short-chain fatty acids (SCFAs). They are thought to contribute to up to 10% of human energy requirements and are key regulators of gut homeostasis. Studies have reported reduced levels of SCFAs in AN patients.
Intestinal permeability and immune mechanisms
Gut microbiota alterations observed in AN are indicated to contribute to increased intestinal permeability. This facilitates the translocation of bacterial products into the systemic circulation and thus can lead to aberrant immune responses. A ‘leaky gut’ is thought to underlie the elevated risk for autoimmune diseases found in AN.
It is difficult to disentangle cause from effect based on findings from observational studies. However, a recent study in mice showed that when faecal samples from anorexia patients were transferred to the guts of mice, the mice gained less weight and developed more compulsive behaviours compared to mice that received samples from healthy patients.
Gut microbiome research in AN is still in its infancy. Nonetheless, evidence is accumulating that supports the role of intestinal dysbiosis in AN. While these results are preliminary, they open the possibility to targeting the microbiome as a viable treatment for anorexia. Further exploration of the dynamics between the gut microbiome, environment and genetics will help guide the development of these interventions to more effectively address the comorbidities and high relapse rate of this disorder.
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