Abstract
There are numerous downstream consequences of marketed drugs like antineoplastic agents on the gut microbiome, an effect that is suggested to contribute to adverse event profiles and may also influence drug responses. In cancer, progress is needed toward modulation of the host microbiome to prevent off-target side effects of drugs such as gastrointestinal mucositis that result from gut dysbiosis. The objective of this study was evaluation of the bioactivity of a supplement consisting of capsules with a blend of 9 probiotic organisms of the genera Lactobacillus and Bifidobacterium plus 10 digestive enzymes, in protecting the human gastrointestinal tract from chemotherapy and an antibiotic. We used the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model, an in vitro model of a stable colon microbiota, and introduced 5-fluorouracil (5-FU) and vancomycin as microbiome-disrupting drugs. The probiotic with digestive enzymes supplement, added in capsules at in vivo doses, improved fermentation activity in the colon reactors and accelerated the recovery of microbial populations following 5-FU/vancomycin treatment. The supplement restored the Bacteroidetes to Firmicutes ratios in the colon reactors, increased the diversity of microbiota, and induced the production of microbial metabolites that elicited anti-inflammatory cytokines in an in vitro model of intestinal inflammation. In the proximal colon, preventative administration of the supplement resulted in full recovery of the gut microbial community after cessation of 5-FU and vancomycin treatment. These results identify a probiotic with digestive enzymes formulation that protects against drug-induced gut dysbiosis, highlighting its potential utility as a component of routine cancer care.