Altered Fecal Metabolites and Colonic Glycerophospholipids Were Associated With Abnormal Composition of Gut Microbiota in a Depression Model of Mice

Abstract

The microbiota–gut–brain axis has been considered to play an important role in the development of depression, but the underlying mechanism remains unclear. The gastrointestinal tract is home to trillions of microbiota and the colon is considered an important site for the interaction between microbiota and host, but few studies have been conducted to evaluate the alterations in the colon. Accordingly, in this study, we established a chronic social defeated stress (CSDS) mice model of depression. We applied 16S rRNA gene sequencing to assess the gut microbial composition and gas and liquid chromatography–mass spectroscopy to identify fecal metabolites and colonic lipids, respectively. Meanwhile, we used Spearman’s correlation analysis method to evaluate the associations between the gut microbiota, fecal metabolites, colonic lipids, and behavioral index. In total, there were 20 bacterial taxa and 18 bacterial taxa significantly increased and decreased, respectively, in the CSDS mice. Further, microbial functional prediction demonstrated a disturbance of lipid, carbohydrate, and amino acid metabolism in the CSDS mice. We also found 20 differential fecal metabolites and 36 differential colonic lipids (in the category of glycerolipids, glycerophospholipids, and sphingolipids) in the CSDS mice. Moreover, correlation analysis showed that fecal metabolomic signature was associated with the alterations in the gut microbiota composition and colonic lipidomic profile. Of note, three lipids [PC(16:0/20:4), PG(22:6/22:6), and PI(18:0/20:3), all in the category of glycerophospholipids] were significantly associated with anxiety- and depression-like phenotypes in mice. Taken together, our results indicated that the gut microbiota might be involved in the pathogenesis of depression via influencing fecal metabolites and colonic glycerophospholipid metabolism.

Multi-omics data reveals the important role of glycerophospholipid metabolism in the crosstalk between gut and brain in depression

“…Liu et al found the disturbance of GP metabolism in the plasma of depression patients, and identified several GPs as potential biomarkers to diagnose depression [ 37 ]. In our previous studies, we found the changes of some GPs in the urine and serum of depression patients [ 18 – 20 ] and in the liver and colon of depressed mice [ 22 , 28 ]. Researchers have reported that there are obvious disturbances of lipid metabolism in depression [ 38 , 39 ], but its specific role in the onset of depression is still unclear.…”

“…The procedures of 16S rRNA gene sequence analysis and metagenomic analysis of fecal samples were exactly according to our previous studies (Additional File 1 ) [ 13 , 14 , 28 , 29 ]. Meanwhile, the lipidomics analyses of fecal sample were performed using liquid chromatography-mass spectrometry (LC-MS), and the procedure was also exactly according to our previous studies (Additional File 1 ) [ 13 , 14 , 29 ].…”

Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population

“…Additionally, we observed alterations in fecal lipid metabolites, which could be attributed to the observed dietary changes that included decrease in total fat and increase in monounsaturated fat consumption. On the other hand, recent studies have reported potential associations between changes in lipid metabolites and depression-like behavior in mice [ 67 ] as well as post-stroke depression [ 68 ], suggesting that the microbiota might influence mood through regulation of lipid metabolism. While these observations allow us to formulate exciting hypothesis, the physiological significance of these findings remains to be determined, as we could not associate the urine or fecal metabolites with changes in PSS.…”

Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role

“…According to researchers' speculation, acupuncture restored gut flora balance primarily by regulating glycerophospholipid metabolism and primary bile acid biosynthesis. Several studies have shown that intestinal microflora is involved in the pathogenesis of depression 10.3389/fnins.2023.1146946 through glycerophospholipid metabolism and primary bile acid biosynthesis (Gong et al, 2021;MahmoudianDehkordi et al, 2022). Accordingly, it can be speculated that electroacupuncture might be useful in treating depression by regulating intestinal flora's production of glycerophospholipids and bile acids.…”