A recent study, led by Dr. Peng Xie from the Chongqing Medical University in China, has demonstrated that intestinal ‘dysbiosis’ may have a causal role in the development of depressive-like behaviours in mice through altering host metabolism.
It has been previously described that the gut microbiota may be an environmental factor that can modulate brain physiology through the microbiota-gut-brain axis. Zheng and colleagues have demonstrated that the absence of gut microbiota in germ-free (GF) mice led to a decreased depression-like behaviour as evidenced by a significantly decreased immobility time in the forced swimming test—used as an index of depression-like behaviour—compared with their conventionally raised specific pathogen-free (SPF) counterparts. These results suggest a link between the microbiota-gut-brain axis and depression-like behaviour.
In addition, the researchers showed that patients with major depressive disorder (MDD) (n= 58) exhibited significant alterations in their gut microbiota relative to healthy controls (n = 63). Decreased microbial diversity in MDD patients were characterized by alterations in the relative abundances of the phyla Firmicutes, Actinobacteria and Bacteroidetes. However, these results are not consistent with a previous study by Jiang et al. in which increased faecal bacterial diversity was found in the active-MDD vs. the healthy control group but not in the responded-MDD vs. the healthy control group. Bacteroides, Proteobacteria, and Actinobacteria increased in level, whereas that of Firmicutes was reduced in MDD groups compared with the healthy control group.
When mice were transplanted the microbiota of MDD patients (n=5) this induced depression-like behaviours in GF recipient mice, while transplantation of the microbiota of healthy controls (n=5) did not induce such behavioural changes. Characteristics of the gut microbiota responsible for distinguishing depressed from healthy humans were also observed in recipient mice. The mice harbouring the gut microbiota from MDD patients exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. These results demonstrate that the role of gut microbiota in the development of depressive-like behaviours may be mediated through alterations in the host’s metabolism.
In sum, gut microbiota can contribute to depression-like behaviour in mice through altering host metabolism. These findings, if found to be applicable to humans, could provide a new approach for depression therapies.
Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry. 2016; 1-11. doi: 10.1038/mp.2016.44.