Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

Abstract

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%, *P<0.05). BBR (100 mg/kg/day, orally) decreased blood lipids in the HFD-fed hamsters (**P<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 (**P<0.01). Similarly, after oral administration, the blood level of BBR in hyperlipidemic patients was higher than that in healthy individuals (*P<0.05). Correlation analysis revealed a positive relationship between blood BBR and fecal NR activity (r=0.703). Thus, the fecal NR activity might serve as a biomarker in the personalized treatment of hyperlipidemia using BBR.

Drug–gut microbiota interactions: implications for neuropharmacology

“…Increased dietary protein, leading to increased arginine, could thus constitute a potential dietary intervention to improve digoxin efficacy. Recent data have also elucidated the role of diet‐induced changes in the gut microbiota on the oral bioavailability of the herbal supplement, berberine, used for the treatment of hyperlipidaemia and type 2 diabetes (Wang et al ., ). The bioavailability of berberine was significantly increased in high‐fat diet (HFD)‐fed hamsters in comparison to hamsters fed a normal diet.…”

Effect of Berberine on Atherosclerosis and Gut Microbiota Modulation and Their Correlation in High-Fat Diet-Fed ApoE−/− Mice

“…Nutraceuticals containing BBR can significantly reduce plasma LDL-C levels of elderly statinintolerant hypercholesterolemic patients (Marazzi et al, 2011). Another study showed that when it plus low-dose statins and/or ezetimibe, most coronary artery disease (CHD) patients who were high-dose statin intolerant could achieve target LDL-C levels within 3 to 6 months (Marazzi et al, 2019).Of note, the therapeutic effects of BBR on these inflammatory and metabolic diseases, such as emergent mild diarrhea (Yue et al, 2019), ulcerative colitis (Cui et al, 2018), obesity (Xie et al, 2011;Zhang et al, 2015), hyperlipidemia (Wang et al, 2017) and diabetes , appeared to be related to the regulation of the gut microbiota.…”

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

“…Recently, E. coli infection was observed to significantly reduce the absorption of orally administered enrofloxacin in broilers (Guo et al, 2014). Yan Wang reported that berberine treatment lowered blood lipids and glucose effectively only in the high-fat diet (HFD)-fed hamsters with increased levels of nitrate reductase (NR) activity in the gut microbiota (Wang et al, 2017). In our previous research work, liver injury affects the gut microbiome in rats, particularly by depleting the Lactobacillus, which is directly involved in the bioconversion of the GL.…”

“…Rats pretreated with L. murinus or normal saline (n = 6) were administered an oral (10 mg/kg) dose of GL dissolved in 0.5% sodium carboxymethyl cellulose (CMC-Na) (5 mg/ml) 24 h after completing the seven consecutive daily treatment with physiological saline (control) or L. murinus dissolved in physiological saline (1 × 10 9 CFU/mouse). Whole-blood samples were taken from the orbital vein into tubes with heparin sodium at 0.17, 0.33, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72 h after oral administration (Zhou et al, 2013;Wang et al, 2017). Plasma was harvested by centrifugation at 8,000 rpm for 10 min and stored at −20 • C until analyzed.…”