Effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics in a high-cholesterol diet-induced hypercholesterolemia rat model.

OBJECTIVES: The aim of this study was to evaluate effect of Lactobacillus plantarum HT121 on serum lipid profile, gut microbiota, and liver transcriptome and metabolomics. METHODS: L. plantarum HT121 was selected by screening of acid and bile salt tolerance and cholesterol assimilation assay. Sprague Dawley rats were randomly divided into three groups and fed the respective diets for 7 wk: normal chow diet (NCD), high-cholesterol diet (HCD), and high-cholesterol diet plus L. plantarum HT121 (HT121). After 7 wk, blood lipid profile was measured by enzyme-linked immunosorbent assay, gut microbiota was determined by 16 S rRNA sequencing, gene expression, and bile acids in liver were detected by transcriptome and metabolomics, respectively. RESULTS: L. plantarum HT121 feeding decreased serum triacylglycerols (TGs), total cholesterol (TC), and low-density lipoprotein (LDL), and increased serum high-density lipoprotein levels. HT121 treatment increased the α-diversity in the HT121 group to a level close to that in the NCD group, and restored the genera of Adlercreutzia, Mucispirillum, Ruminococcus, Clostridium, Blautia, Roseburia, and Akkermansia to levels similar to those in the NCD group. Furthermore, the high-cholesterol diet decreased taurocholic acid (TCA) and increased taurochenodeoxycholic acid (TCDCA) and glycocholic acid (GCA) in the liver; all these changes were reversed by HT121 treatment, bringing the levels close to those in the NCD group. Finally, HT121 treatment increased expression of bile secretion-related genes Cyp7 a1 in rat liver, which was positively correlated with TG, Clostridium, and GCA. Spearman's correlation analysis showed that TGs, TC, and LDL were positively correlated with the relative abundance of genera of Blautia, Clostridium, and Roseburia, and levels of bile acid glycocholic acid, and inversely correlated with the relative abundance of Ruminococcus and Mucispirillum. CONCLUSIONS: L. plantarum HT121 can improve serum lipid profiles in a high-fat diet-induced rat model, which may be attributed to alteration in gut microbiota and bile acid metabolism.

Short Term Intrarectal Administration of Sodium Propionate Induces Antidepressant-Like Effects in Rats Exposed to Chronic Unpredictable Mild Stress.

Depression has been correlated with metabolic disorders, and the gut microbiota and its metabolites have been reported to be key factors affecting metabolic disorders. Several metabolites generated by the gut microbiota have been reported to exert antidepressant-like effects, including the short chain fatty acid (SCFA) butyrate. However, recent work has suggested that the abundance of butyrate is not significantly changed in neither human nor experimental animals with depression, and butyrate has been reported to decrease upon the administration of prebiotics with antidepressant-like effects. Supplementation of endogenous metabolites that are unchanged in depression may induce additional metabolic disorders and may lead to poorer clinical outcomes. However, the endogenous metabolites that are imbalanced in depression may include several antidepressant candidates that could circumvent these problems. In this study, we used GC-MS spectrometry to study the fecal metabolome of rats under Chronic Unpredictable Mild Stress (CUMS). We carried out static and dynamic metabolomics analyses to identify the differential metabolites between the CUMS rats and control rats. We identified propionic acid, rather than butyric acid, as a differential metabolite of the CUMS rats. Consistent with this, a 1-week intrarectal administration of sodium propionate (NaP, the salt form of propionic acid) induced antidepressant-like effects and partially rebalanced the plasma metabolome. The antidepressant-like effects of NaP were correlated with differential rescue of neurotransmitters in the prefrontal cortex, which may be achieved through the reduction of catabolism of noradrenaline, tryptophan and dopamine, rather than serotonin. These findings support NaP as a potential candidate in fighting depression by administering an endogenous metabolite.