Cancer and Inflammation Program, NCI, NIH, USA
Title: Gut microbiota modulates cisplatin mediated systemic toxicity
Biography: Soumen Roy
Anticancer chemotherapy has achieved a significant milestone in increasing the number of cancer survivors over past decades, while leaving behind the survivors with various toxic side effects, which are nephrotoxicity, ototoxicity and intestinal damage. Challenges remain to reduce systemic toxicity as well as retaining the anticancer therapy. Gut microbiota modulates cancer chemotherapy, however little is known about the role of gut microbiota in modulating systemic toxicity. We hypothesized that gut microbiota regulates systemic toxicity. Four groups (n=10/group) of 8 weeks old C57B/6 mice were treated with cisplatin, cisplatin+antibiotics cocktails (ABX), ABX only and untreated. ABX cocktail contained primaxin, vancomycin and neomycin, which depletes broad spectrum gut microbiota. This experiment was validated using C57B/6 germ free mice (contains no microorganisms). We performed anti-p-γ-H2AX and anti-ATM based DNA-double stranded break (stains foci in the nuclei) based toxicity assay in kidney and gut (small bowel). H&E and 4 color immunostaining (anti-p-γ-H2AX, anti-ATM, Actin and DAPI) were done. DNA-DSBs were evaluated using Zeiss 780 confocal and quantified by 3-D reconstruction using IMARIS. There were reductions in γ-H2AX+ DAPI+ (DNA damaged) cell populations compared to only cisplatin treated mice, indicated protection in the kidney. Both nuclear foci counts as well as the pathological scores indicated gut microbiota associated modulation in the glomeruli of kidney and in the villi of small bowel. Our data leads to a possibility to develop microbiota based therapy which might be utilized to reduce chemotherapy associated systemic toxicity and for better management of chemotherapy.