Gut dysbiosis in mania: A viable therapeutic target?

To the Editor

An intriguing report in this Journal described a previously well 46-year-old woman, with no history or family history of mental disorder, who was admitted for a first manic episode 2 weeks after bariatric surgery (Hamdani et al., 2015). Treated with activated charcoal, the patient’s symptoms resolved over the next fortnight and she remained well over the following few months. This improvement was concurrent with decreases in biomarkers of inflammation, which were elevated on admission.

While there are some limited data to suggest that bariatric surgery modifies gut microbiota composition, it is not clear as yet whether these changes are cause or consequence of dietary changes and/or weight loss secondary to the surgery or specific consequences of the surgery itself. In fact, bariatric surgery has been shown to be associated with decreased low-grade systemic inflammation over time, but this appears to be driven by changes in diet or weight following surgery (Dalmas et al., 2011). In this case, the patient had only had the surgery 15 days prior, her body mass index (BMI) was 36 on admission and remained stable and all nutrient levels were normal. As such, it is unlikely that weight loss or dietary change was the reason for possible microbial and inflammatory changes. However, anesthetics and surgery both markedly increase inflammation and oxidative stress, and diverse traumas increase gut permeability, facilitating translocation into the systemic circulation and altering the gut microbiome (Earley et al., 2015). This lends credence to the hypothesis of a ‘cytokine storm’ as referred to by the authors.

This notable case report provides support to the contention and emerging evidence suggesting that the gut and its resident microbiota play a role in mood and behavior. However, caution should be employed in applying this treatment more broadly. Firstly, it is possible that the mania may not have been a result of the bariatric surgery or microbiota disruption; inflammation is commonly seen in psychiatric episodes and may have been a result, rather than cause, of illness. Similarly, mania may have resulted from another, unidentified cause. It is characteristically time limited and may have normalized without the use of treatment targeting the microbiota–gut–brain axis. Finally, the cancer-promoting risks of charcoal are documented and this should act as a disincentive to the regular use of activated charcoal. However, this case report offers a potentially important insight into a mechanistic pathway to disease that has not, until very recently, been considered and supports an increased focus on psychiatric treatments targeting the microbiota–gut–brain axis.