Clinical and basic studies have shown the link between gut microbiome and MDD. As the fraction of gut microbiome containing the gene coding for CAZymes, here we charactered how the CAZymes changed in the MDD relative to HC. Interestingly, we found that MDD was associated with enriched Glycoside Hydrolases and Polysaccharide Lyases. A random forest model constructed by 9 CAZymes could effectively distinguish patients with MDD and HC, then the diagnostic performance of this CAZymes panel was independently verified. Meanwhile, based on linear mixed-effects analysis, we found that 4 CAZymes could predict the therapeutic effects in the patients treated with antidepressants. Our research provides new ideas for the accurate diagnosis and treatment of depression. The metagenome data suggest that the gut microbiota of MDD have a greater mucin-utilization capacity relative to HC. It may because of the high concentration of Bacteroides in MDD population. In addition, the increased availability of mucin may weaken the mucous layer of the intestinal wall, and some Bacteroides can degrade mucin during survival, such as B. thetaiotaomicron, B. fragilis, as a result, harmful molecules in MDD are more likely to cross the gut and enter the circulatory or endocrine system [25].
Alternations of gut microbiome were closely related to depression. In the past, we and other teams focused on exploring how the gut bacteria and viruses changed in MDD [15, 26, 27]. In addition, using fecal bacteria transplantation and probiotic intervention, preliminary evidences showed that disturbances of gut microbiome may attribute to development of depression by regulating the MGB axis’ metabolism [28, 29].These studies lay a foundation for further study of the role of gut microbiome in depression. Here, we identified the differentially expressed CAZymes in the patients with MDD relative to HC, hoping to further understand the function of gut microbiome in depression from this new point. Here, we found MDD is substantially linked with alternations of CAZymes relative to HC. Compared to HC, the MDD was characterized by enriched Glycoside Hydrolases and Polysaccharide Lyases. Given Bacteroides, especially Bacteroides thetaiotaomicron and Bacteroides ovatus, dedicate about 6% of their genomes to encode these two CAZymes [8]. These results suggesting that alternations of Bacteroides species was a hallmark of MDD, which was consistent with our previous studies [15, 16].
In addition, we found that the CAZymes has potential diagnostic and predictive value in MDD. For example, CAZymes maker panel enable discriminating the MDD and HC with the values of 0.824, suggesting that it has potential clinical transformation value. Clinically, predicting the efficacy of antidepressants remains challenging prior to antidepressant medication, thus inevitably, the trial and error of experience lies in the replacement of new drugs. Here, we found that markers belonging to Glycoside Hydrolases increased in baseline MDD relative to HC. Interestingly, the baseline level of GH51 was negatively correlated with HAMD (2, 4 and 6weeks) and QIDS (2 and 4weeks) scores. Consistently, PL12_1 was also negatively correlated with these two clinical scores of 6weeks. An enzyme (α-L-arabinofuranosidase) in the GH51 family, encoded by two dominant Bacteroides (B. ovatus V975 and B. thetaiotaomicron VPI-5482) [30, 31].Another CAZyme (PL12_1) contains 2 types of heparin lyase, which were found to be encoded by B. stercoris HJ-15 and B. thetaiotaomicron VPI-5482 [32, 33].These results suggesting alternations between drugs and biological functions of Bacteroides involved in antidepressant effects. Given CAZymes could be detected in feces, it lays a foundation for the development of noninvasive diagnostic and predictive kits.
Our study has the following shortcomings: (1) although a relatively large sample size is used to identify CAZymes as candidate markers, this result still needs to be independently verified by a large multi-center sample; (2) In depth study of the function of CAZymes is expected to further understand the roles of gut microbiome in the pathophysiological mechanisms of MDD; (3) Since CAZymes are mainly involved in the digestion of polysaccharides, it is also worth exploring how to formulate an individualized diet which is more suitable for the microecological health of MDD; (4) Future researches to explore whether intervention of CAZymes has potential therapeutic effects in MDD are required.
In this study, using well-characterized cross-section and longitudinal clinical samples, we provided evidences that MDD was associated with disturbances of gut CAZymes. Moreover, we found that the CAZymes markers can be used to diagnose the patients with MDD and predict antidepressant effects. Our findings suggest that alternations of CAZymes may be a new entry point to understand the roles of gut microbiome in the development of MDD.