Gut Microbes May Influence Chemotherapy Side Effects

Chemotherapy drugs can convert gastrointestinal bacteria into toxic species that causes severe diarrhea.

Some of the debilitating side effects from chemotherapy may be partially influenced by gut microbes, a recent study indicates.

The study, published in Chemistry & Biology, noted that when chemotherapy drugs are eliminated from the body, it can attach to gastrointestinal tract bacteria, which then creates a toxic species that causes severe diarrhea. To combat this effect, researchers explored ways to block gastrointestinal microbes from turning into the toxic species in mice.

"The GI microbiota are the great crowd-sourcers of chemistry, using a dizzying array of enzymes to process drugs and other chemicals, occasionally with terrible consequences," said senior author Matthew Redinbo, of University of North Carolina at Chapel Hill. "We show that the bacteria in the GI contain 'druggable targets,' ones that we can modulate with the same types of small molecule approaches that have transformed other aspects of human health."

Bacteria use the Beta-glucuronidaseconsume enzyme to consume sugar called glucuronic acid. This enzyme collects sugar from small chemicals that enter the gastrointestinal track to be eliminated.

For example, the drug irinotecan links to glucuronic acid to mark it for elimination, however as sugar is removed by gastrointestinal bacteria, a virulently toxic drug is released back into the intestines. This mixture has been found to cause diarrhea in nearly 90% of patients who take irinotecan.

Investigators previously found that inhibiting Beta-glucuronidase can decrease GI toxicity from irinotecan, which indicates the bacteria plays a significant role in the drug's side effects. Researchers noted that this effect may also carry over to nonsteroidal anti-inflammatory drugs with glucuronic acid that may cause gastrointestinal distress.

The researchers characterized various forms of Beta-glucuronidase caused by different gut bacteria strains, which showed that inhibiting gastrointestinal bacterial Beta-glucuronidases in mice has no impact on irinotecan and its ability to fight cancer.