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.
Highlights
The microbiome in the human gut is composed of 500–1000 distinct bacterial species and up to 1014 total bacteria that are responsible for intestinal health and for regulation of the immune system
To further evaluate the impact of the probiotic with digestive enzymes supplement, the series of experiments utilized quantitative PCR (qPCR) to identify changes the microbial composition in the Simulator of Human Intestinal Microbial Ecosystem (SHIME) reactors representing the proximal and distal colon. These analyses focused on looking at the rates of recovery of healthy microbiota following the administration of 5-FU/vancomycin during treatment week 1 (TR1; refer to Figures 3 and 4), where 5-FU/vancomycin was discontinued during the recovery weeks spanning treatment week 2 (TR2)-treatment week 4 (TR4) (Figures 3 and 4)
The test product contains a blend of 9 probiotic organisms of the Lactobacillus and Bifidobacterium genera, as well as 10 digestive enzymes contained in capsules that were administered in an in vitro system to recapitulate the gut microbiome using doses of the product that would be administered clinically
Summary
The microbiome in the human gut is composed of 500–1000 distinct bacterial species and up to 1014 total bacteria that are responsible for intestinal health and for regulation of the immune system. There is a relationship between the lactic acid bacteria and the butyrate producers since the latter utilize lactate [12] On this basis, there are numerous mechanisms by which gut microbiota dysbiosis leads to increased permeability, aberrant immune activation, and chronic inflammation, all of which can contribute to colorectal cancer initiation and progression [1]. There are numerous mechanisms by which gut microbiota dysbiosis leads to increased permeability, aberrant immune activation, and chronic inflammation, all of which can contribute to colorectal cancer initiation and progression [1] This information raises the question as to whether specific probiotic formulations can be used to restore the microbial composition and the beneficial microbial metabolites in the gut Intestinal microorganisms may determine the outcome of cancer treatments as well as being themselves affected by the treatments. Since the duration of gut dysbiosis is a critical factor in managing adverse events of the treatment, evaluation of putative therapies such as probiotics should include monitoring the microbiota dynamics
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