Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers

Abstract

Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe–gut–brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography–mass spectrometry, nuclear magnetic resonance, and liquid chromatography–mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about “depression microbes” impacting on liver metabolism.

Gut Microbiota Is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San

“…Accumulating evidence highlights the potential association of gut microbiota with depression via the microbe-gut-brain axis [6,14,15]. Previous studies revealed altered gut microbiota composition in depression patients and in rodent models [6,7], and here, we confirmed these data in CVS-induced depression rats (Figure 3).…”

Neuroprotective effects of an engineered commensal bacterium in the 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine Parkinson disease mouse model via producing glucagon‐like peptide‐1

“…Besides α‐syn aggregation, mitochondrial functional impairment, endoplasmic reticulum stress, calcium homeostasis, and intestinal dysfunction are regarded significant contributors to the pathogenesis of Parkinson disease (Li et al . ; Soto et al . ).…”

The changes of gut microbiota in drug-naïve first-episode MDD patients under treatment by SSRIs

“…In several paralleled researches, MDD patients showed speci c features of gut microbes differing from normal controls [5][6][7][8]. Several studies have reported that transplantation of stool from MDD patients into rodents could lead to depression-like behaviors, which had be used to establish animal models of MDD [5,9,10]. The similar phenomenon was observed in fecal bacteria transplantation between animal models.…”