5.3 Dysbiosis and Depression
Hannan Algitami
Introduction
As discussed in earlier chapters, the bidirectional relationship between the gut and the brain, or the gut-brain-axis, raises many questions about how brain function is affected by the gut and vice versa. More specifically, the degree to which the gut microbiome is implicated in mental illness has only recently been explored.
Mood disorders such as MDD (Major Depressive Disorder) are idiopathic and have not had a successful targeted treatment mainly because they affect many areas. One of the speculated targets of these disorders is the gut due to the high rates of comorbidity between mental illness and gastrointestinal illness. For instance, many people suffering from IBS (Irritable Bowel Syndrome) also suffer from MDD, with antidepressants being one of the only medications successful in treating IBS. Therefore, there is a clear connection between the gut and mental illness; however, which system is affected first and hence which imbalance leads to the other is yet to be elucidated (Rogers et al., 2016).
To solve this conundrum, researchers from far and wide have attempted to find a relationship between gastrointestinal imbalance and MDD. What was known thus far was that MDD is comorbid with many gastrointestinal disorders and that antidepressants somehow affect the gut and serve as treatments for these disorders. They hence proposed that the gut microbiota must be affected by MDD, which is why antidepressants, acting in most cases to reverse the condition, also bring the MDD-induced changes in the gut back to homeostasis. All of these were mere conjectures and therefore had to be followed up by more investigation.
Dysbiosis and depression
The first area that needed to be addressed was the gut microbial profiles of MDD patients and healthy controls. Comparative analyses using techniques such as 16S rRNA sequencing revealed a significant difference between the gut microbial populations of the two groups (See Figure 1). For example, one study found that MDD patients had a higher relative abundance of Bacteroidetes and a lower relative abundance of Actinobacteria compared to healthy controls (see Chapter 4.1 for details on bacterial phyla) (Zheng et al., 2016a). In addition, another study found that patients with MDD had higher levels of Enterobacteriaceae and Alistipes but lower levels of Faecalibacterium compared to healthy controls (Jiang et al., 2015; Liu, 2017). Moreover, a third study noted higher levels of Bacteroidales but lower levels of Lachnospiraceae in MDD patients compared to healthy controls (Liu, 2017; Naseribafrouei et al., 2014). Hence, there is indeed a relationship between the MDD pathology and the gut microbiome, but the direction in which this relationship goes is unknown.
To attempt to find out the direction of this complex relationship, researchers manipulated the gut microbiome composition in a number of ways and observed the behavioural and physiological changes that