Major depressive disorder (MDD), which affects >350 million people worldwide, has become one of the most challenging public health problems owing to its extraordinary economic burden on society and productivity loss in patients (Ye et al., 2021; Malhi and Mann, 2018; WHO, 2017). In 2020, 28 % of new cases of MDD have increased globally due to the COVID-19 pandemic, of which the proportion of women was approximately twice that of men (COVID-19 Mental Disorders Collaborators, 2021). Of note, depression rates in teenagers have drastically increased in the past decade, especially in females (WHO, 2017; Moffitt et al., 2010; Kessler and Bromet, 2013; Hirschfeld, 2012).

Currently, the International Classification of Diseases and Related Health Problems, 11th revision (ICD-11) and American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) are mainly used as diagnostic criteria to estimate depression state internationally (WHO, 2019; American Psychiatric Association, 2013). However, as a heterogeneous disease with multiple pathophysiological mechanisms, depression is not simply a mood disorder (Malhi and Mann, 2018). The variable etiological hypotheses of depression include the monoamine theory, hypothalamic-pituitary-adrenal (HPA) axis changes, inflammation, neuroplasticity and neurogenesis, gut-brain axis regulation, and brain structural changes (Malhi and Mann, 2018). Recently, the potential relationship between depression and gut dysbiosis has been proven by ample experimental and clinical data (Simpson et al., 2021; Cryan et al., 2020).

The bidirectional communication between the brain and gut has long been recognized, via the autonomic and enteric nervous systems, neuroendocrine system, and immune system (Sgritta et al., 2019; Lyte, 2014). Notably, the gut microbes are prolific producers of diverse chemical metabolites that serve as versatile messengers in host interaction (Snigdha et al., 2022). Numerous metabolic pathways subjected to host and microbe co-regulation are linked to the onset of anxiety and depression-like behaviors (Simpson et al., 2021). The imbalance of neurotransmitters in the tryptophan (TRP) metabolic pathway is considered a vital risk factor in psychiatric diseases (Silber and Schmitt, 2010). Among them, serotonin (5-hydroxytryptamine [5-HT]), a monoamine neurotransmitter through TRP metabolism, has attracted much more attention. However, the influence of the TRP metabolic pathway has far exceeded that of previous studies focusing on 5-HT metabolism, and two other key branches of TRP, the kynurenine pathway (KP) and the indole pathway (IP), are involved in neuroendocrine activities. Notably, kynurenine (KYN) metabolism accounts for 95 % of TRP substrates (Platten et al., 2019), and some of its metabolites can pass through the blood-brain barrier, which is closely related to the occurrence and development of depression (Walker et al., 2019; Brown et al., 2021). However, the full metabolic profile of the KP along the microbiota-gut-brain (MGB) axis in depression remains poorly understood.

The immaturity of the microbiota state of adolescents is more likely to be affected by environmental stressors, leading to inflammation and other problems (Kamimura et al., 2019; Tsilimigras et al., 2018). Reciprocally, probiotics harbor the salutary benefits for central nervous system diseases through the gut-brain axis, such as anxiety, depression, autism spectrum disorder and Parkinson's disease (Snigdha et al., 2022). For example, the abundance of Coprococcus in the intestine of patients with depression is positively correlated with quality of life (QoL) (Valles-Colomer et al., 2019). In the current study, the potential probiotic Coprococcus was screened via the comparison between healthy and unmedicated depressive adolescents. Through the Coprococcus eutactus (C.e.) transplantation, the neurotransmitter homeostasis of the TRP and tyrosine (TYR) metabolic pathways along the gut-brain axis were examined in chronic restraint stress (CRS) induced depression mice. Moreover, the impairments of the synapses, colon integrity, and the microbiota dysbiosis were also investigated, aiming to unravel the salutary roles of C.e. in the MGB axis.