Abstract
Many pharmaceutical agents not only require microbial metabolism for increased bioavailability and bioactivity, but also have direct effects on gut microbial assemblage and function. We examined the possibility that these actions are not mutually exclusive and may be mutually reinforcing in ways that enhance long‐term of these agents. Daikenchuto, TU‐100, is a traditional Japanese medicine containing ginseng. Conversion of the ginsenoside Rb1 (Rb1) to bioactive compound K (CK) requires bacterial metabolism. Diet‐incorporated TU‐100 was administered to mice over a period of several weeks. T‐RFLP and 454 pyrosequencing were performed to analyze the time‐dependent effects on fecal microbial membership. Fecal microbial capacity to metabolize Rb1 to CK was measured by adding TU‐100 or ginseng to stool samples to assess the generation of bioactive metabolites. Levels of metabolized TU‐100 components in plasma and in stool samples were measured by LC‐MS/MS. Cecal and stool short‐chain fatty acids were measured by GC‐MS. Dietary administration of TU‐100 for 28 days altered the gut microbiota, increasing several bacteria genera including members of Clostridia and Lactococcus lactis. Progressive capacity of microbiota to convert Rb1 to CK was observed over the 28 days administration of dietary TU‐100. Concomitantly with these changes, increases in all SCFA were observed in cecal contents and in acetate and butyrate content of the stool. Chronic consumption of dietary TU‐100 promotes changes in gut microbiota enhancing metabolic capacity of TU‐100 and increased bioavailability. We believe these findings have broad implications in optimizing the efficacy of natural compounds that depend on microbial bioconversion in general.
Highlights
Enteric microbiota exerts diverse and profound effects on the physiology of the host
Fecal samples collected from mice with or without dietary TU-100 over 1 month were first examined by Terminal restriction fragment length polymorphism (T-RFLP) analysis
A significant increase is observed in a number of genera including Lactococcus sp. (Table 2) as well as four species of Clostridium subcluster XIVa (Clostridium clostridioforme, Clostridium populeti, Roseburia intestinalis, and Eubacterium hallii) (Collins et al 1994; Barcenilla et al 2000) known to produce short-chain fatty acids, including butyrate and acetate
Summary
Enteric microbiota exerts diverse and profound effects on the physiology of the host. Many factors influence the composition of the intestinal microbiome including dietary components such as lipid and carbohydrate, as well as medical compounds that increase or decrease the survival and growth of specific types of bacteria. Bacteria have diverse metabolic activities and are required for metabolism of many endogenous and xenobiotic substances prior to intestinal absorption, increasing bioavailability. One xenobiotic compound where bacterial metabolism is essential for intestinal absorption is the ginseng saponin, ginsenoside Rb1 (Rb1) (Wang et al 2011). Rb1 is a major saponin of all ginseng, produced at high levels by Wisconsin (Panax quinquefolius) and Asian ginseng (Panax ginseng), but present in all of the genus Panax members. Roots of most Panax are fleshy and have been used in traditional medical uses for thousands of years and contain the high levels of ginsenoside Rb1
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