Transforming berberine into its intestine-absorbable form by the gut microbiota

Abstract

The gut microbiota is important in the pathogenesis of energy-metabolism related diseases. We focused on the interaction between intestinal bacteria and orally administered chemical drugs. Oral administration of berberine (BBR) effectively treats patients with metabolic disorders. However, because BBR exhibits poor solubility, its absorption mechanism remains unknown. Here, we show that the gut microbiota converts BBR into its absorbable form of dihydroberberine (dhBBR), which has an intestinal absorption rate 5-fold that of BBR in animals. The reduction of BBR to dhBBR was performed by nitroreductases of the gut microbiota. DhBBR was unstable in solution and reverted to BBR in intestine tissues via oxidization. Heat inactivation of intestinal homogenate did not inhibit dhBBR oxidization, suggesting the process a non-enzymatic reaction. The diminution of intestinal bacteria via orally treating KK-Ay mice with antibiotics decreased the BBR-to-dhBBR conversion and blood BBR; accordingly, the lipid- and glucose-lowering efficacy of BBR was reduced. Conclusively, the gut microbiota reduces BBR into its absorbable form of dhBBR, which then oxidizes back to BBR after absorption in intestine tissues and enters the blood. Thus, interaction(s) between the gut microbiota and orally administrated drugs may modify the structure and function of chemicals and be important in drug investigation.

Effects of Lactic Acid Bacteria‐Fermented Soymilk on Isoflavone Metabolites and Short‐Chain Fatty Acids Excretion and Their Modulating Effects on Gut Microbiota

“…Antibiotics intervention exhibited similar results to previous studies, resulting in a remarkable decrease in gut bacterial diversity and a significant change in bacterial community structure and composition (Feng et al, 2015). Fermented soymilk intake showed no protective effect on the decreased bacterial richness caused by antibiotics intervention, but a slight increase of Simpson index was observed, suggesting an improved bacterial diversity by fermented soymilk consumption.…”

Gut Microbiota-Mediated Personalized Treatment of Hyperlipidemia Using Berberine

“…Although the NR information for some of these bacteria is not available, Enterobacter has been reported to be a NR-producer 28. Indeed, our previous results demonstrated that the Enterobacter cloacae of the gut microbiota efficiently converted BBR to dhBBR 17. Thus, the composition analysis of gut microbiota confirmed the difference of gut flora between healthy subjects and patients with hyperlipidemia which might contribute to the elevated level of NR in intestine.…”

“…Liquid chromatography with tandem mass spectrometry (LC-MS/MS 8050, Shimadzu Corporation, Kyoto, Japan) and gas chromatography with mass spectrometry (GC-MS QP2010, Shimadzu Cooperation, Kyoto, Japan) were used for the analysis and quantification of BBR and its metabolites in biological samples 14, 17, 20.…”

“…Blood BBR was quantified 14, 17, 41. Plasma (100 μL) was extracted with 1.25 mL ethyl ether after addition of 10 μL internal standard (250 ng/mL of palmatine) and 50 μL 0.5 M sodium hydroxide solution.…”

Traditional Chinese Medicine and Gut Microbiome: Their Respective and Concert Effects on Healthcare

“…Additionally, oral administration with Bifidobacterium bifidum and L. acidophilus, a probiotic combination, was found to prevent intestinal toxicity in cancer patients who were treated with both cisplatin and radiotherapy (Chitapanarux et al, 2010). In addition to the direct effects on the enzymes and microbiome on the absorption and metabolism of drugs (Maurice et al, 2013;Feng et al, 2015;Montassier et al, 2015), the indirect effects of gut microbiome on the metabolism of drugs were reported to occur through regulation of gene expression and the physiological function of the local mucosal barrier and of distant organs, such as the liver (Bjorkholm et al, 2009;Selwyn et al, 2015;Selwyn et al, 2016).…”