Geriatric depression: gut microbiota involved in remission?
Already implicated by previous studies in neuropsychiatric functioning, the gut microbiota may also predict treatment response in geriatric depression, even for treatment with a placebo. Moreover, it may also be predictive of subsequent remission.
A major public health issue, geriatric depression may affect up to 25% of elderly people, with lower remission rates and higher relapse rates than in younger adults. This has led to a search for biomarkers predictive of responses to antidepressants. Unsuccessful to date, this search has now reached a turning point. Based on the fact that brain-gut-microbiota interactions modulate mood disorders and that gut dysbiosis appears in late life, researchers have hypothesized that the gut microbiota may predict responses to antidepressant treatments in geriatric depression. The secondary analysis of a randomized controlled trial (12 weeks of Levomilnacipran [LVM] or a placebo) in California involving seniors with major depressive disorder seems to support this hypothesis.
Bacterial genera capable of predicting remission
As no differences were observed in remission rate between the LVM group and the placebo group, the analysis combined the 4 treated patients and the 8 controls. Of these 12 seniors, 5 overcame their depression (score ≤ 6 on the Hamilton scale): they were younger (67 vs. 74 years) and all were male; but there were no differences in pretreatment gut microbiota alpha or beta-diversity between the two groups. However, the content of 9 bacterial genera in the baseline microbiota was accurate in predicting remission. A significant content of Faecalibacterium, and to a lesser extent Agathobacter and Roseburia, was associated with remission.
A gut microbiota that changes in the case of remission
The study also showed that the gut microbiota of remitters (but not that of non-remitters) changed during their recovery from depression. The researchers observed an increase in certain taxa, including Flavonifractor and DTU089. According to the authors, the increased presence of these bacteria may be the result of depression remission (better diet, increased physical activity, improved sleep, reduced stress, etc.), although they have no known antidepressant effects.
Personalized medicine to treat geriatric depression soon at hand?
Despite this, the relationship between the gut microbiota and depression in aging remains poorly understood. Does a slow decline in the immune system (immunosenescence) lead to a progressive increase in chronic inflammation? Does this increase alter the gut microbiota (loss of diversity)? While questions remain, this is the first study demonstrating that the gut microbiota can predict treatment response in geriatric depression, even for treatment via a placebo. If these results are confirmed by larger prospective studies, they could pave the way for personalized medicine capable of selecting the appropriate antidepressant based on the microbiota and predicted efficacy, or of treating depression by reinforcing certain beneficial taxa.