5-Fluorouracil and irinotecan (SN-38) do not modulate the gut microbiome composition and activity in the absence of a host sytem

Introduction : The Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME) simulates the human gut environment with a focus on the microbial colonization in the colon, both in the luminal and mucosal environment. It can be used to study the effect of various compounds on the intestinal microbiota, without including a host system. Objectives : Our aim is to explore the direct effects of multiple doses of both 5-FU and SN-38 (active metabolite of irinotecan) on the complex gut community of the SHIME to monitor microbial changes after a 1-week exposure to the drugs. Methods : A continuous M-SHIME system was used to culture both luminal and mucosal bacteria and to expose them to multiple doses of physiologically relevant concentrations of 5-FU or SN-38. The effect of both drugs was tested on the fecal material of 5 healthy donors. The effect on the metabolic activity of the microbiota was assessed by short-chain fatty acid analysis. The effect on the microbial community was investigated using 16S r-RNA DGGE. Results : Short chain fatty acid profiles showed no differences after exposure to 5-FU or SN-38, compared to the control SHIMEs. Only minor changes were detected in microbial community composition after 5-FU or SN-38 exposure. Conclusions : No significant effects on the function or composition of the gut microbiota of the donors were observed after exposure to chemotherapeutic drugs. Since clinical studies have repeatedly shown that the composition of the gut microbiome changes after chemotherapy, our data suggest that signalling via the host is necessary to induce these changes.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/2cMzRjQ
via IFTTT