Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine.

Nitroreductases (NRs) are bacterial enzymes that reduce nitro-containing compounds. We have previously reported that NR of intestinal bacteria is a key factor promoting berberine (BBR) intestinal absorption. We show here that feeding hamsters with high fat diet (HFD) caused an increase in blood lipids and NR activity in the intestine. The elevation of fecal NR by HFD was due to the increase in either the fraction of NR-producing bacteria or their activity in the intestine. When given orally, BBR bioavailability in the HFD-fed hamsters was higher than that in those fed with normal chow (by +72%, *<0.05). BBR (100 mg/kg/day, orally) decreased blood lipids in the HFD-fed hamsters (**<0.01) but not in those fed with normal diet. Clinical studies indicated that patients with hyperlipidemia had higher fecal NR activity than that in the healthy individuals (**<0.01). Similarly, after oral administration, the blood level of BBR in hyperlipidemic patients was higher than that in healthy individuals (*<0.05). Correlation analysis revealed a positive relationship between blood BBR and fecal NR activity (=0.703). Thus, the fecal NR activity might serve as a biomarker in the personalized treatment of hyperlipidemia using BBR.