*3.1. Microbiota-Orientated Therapies and Their Interest for Major Depression*

Irritable bowel syndrome is considered as a paradigmatic microbiota-induced illness. We have published a meta-analysis suggesting that patients with irritable bowel syndrome were at higher risk of major depression [37], confirming the potential causal or bilateral relationship between microbiota disturbances and major depression. Several studies have shown microbiota disturbances in patients with major depression; these disturbances are summarized in Table 1 [38–50].


*Nutrients* **2020**, *12*, 1024


**Table 1.** *Cont.*




predictor of depression remission at discharge.

**Table1.***Cont.*



MDD: Major depressive disorder. IBS: irritable bowel syndrome. HCs: Healthy controls. BMI: body mass index.

amplicons

microbiota.

Units associated with depression.

The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments in this indication. Probiotics have yielded medium-to-large significant effects in the setting of depression (d = −0.73 (95% CI = −1.02–−0.44)) in a recent meta-analysis [51]. Approximately half of all existing studies were published over the past two years, reflecting the rapidly growing interest in this area. At the time of this submission, 29 studies involving 3088 participants were published so far. Duration of probiotic administration across trials ranged from 8 days to 45 weeks, whereas it is still unclear if the effect is maintained following probiotic discontinuation.

Two factors may limit MD improvement when probiotics are administered: (1) the small number of bacterial strains administered in probiotic complementary agents (often only one to five bacterial strains including *Lactobacilli*, either alone or in combination with *Bifidobacterium*), and (2) the presence of a disturbed gut microbiota that limits probiotics' efficacy (the so-called gut microbiota "resilience"). Cleaning up the gut microbiota and transplanting a totally new human gut microbiota in one shot (the so-called fecal microbiota transplantation) would thus strongly improve the effect size.
