Gut microbiome-metabolomics integration explores the adjunctive effect of Naoxintong capsule on atorvastatin in...

Naoxintong Capsule (NXT), a prescribed traditional Chinese medicine (TCM), has been widely used in combination with Western medicine to treat patients with atherosclerotic cardiovascular diseases. The purpose of this study was to preliminarily investigate the effects and mechanisms of the addition of NXT to statin therapy in patients with hyperlipidemia.

Thirty-two hyperlipidemia patients were randomly divided into two groups, which received atorvastatin and NXT plus atorvastatin treatment for 12 weeks respectively. The primary outcome was the change of lipid metabolism. Other outcomes included changes in inflammation, endothelial function, liver function and myocardial enzyme. Microbiome and metabonomics analysis were conducted to explore the potential mechanism of the effect of the addition of NXT to atorvastatin.

Compared to atorvastatin monotherapy, the combination therapy demonstrated an 11.3% greater reduction in LDL-C level (2.65 vs. 2.99 mmol/l, p = 0.027), a 24.7% increase in HDL-C level (1.06 vs. 0.85 mmol/l, p = 0.011) and an 18.8% greater reduction in TG (1.77 vs. 2.18 mmol/l, p = 0.011). Systemic anti-inflammatory benefits were evidenced by an 11.8% reduction in IL-6 (69.13 vs. 78.39 ng/l, p < 0.001) and a 10.4% decrease in TNF-α (90.16 vs. 100.63 ng/l, p = 0.030). Additionally, myocardial injury biomarkers showed marked improvement, with a 19.3% decrease in LDH (193.60 vs. 239.96 U/l, p < 0.001) and a 26.2% reduction in CK-MB (31.69 vs. 42.90 U/l, p < 0.001). Some key bacteria of Streptococcus_salivarius, Veillonella_parvula, Streptococcus_thermophilus, Anaerobutyricum_hallii and Ruminococcus_sp_5_1_39BFAA were discovered to be related to the enhanced effect of NXT to atorvastatin via the correlation analysis. Several metabolic pathways, such as citrate cycle, ether lipid metabolism, propanoate metabolism, and glutathione metabolism were uncovered to be closely involved in the outcome of NXT combination treatment.

Taken together, our study demonstrates that the addition of NXT to atorvastatin could enhance the therapeutic effect against hyperlipidemia, which might be related to the composition alterations of gut microbiota and changes in plasma metabolite abundances. This study provides a novel perspective for understanding the mechanism of NXT in the combination treatment of hyperlipidemia in clinic. (Trial registration No. ChiCTR2500097533).