In the human gut, good bacteria are great neighbors.
A new study from Northwestern University found that specific types of gut bacteria can protect other good bacteria from cancer treatments, reducing harmful drug-induced changes in the gut microbiome. By metabolizing chemotherapy drugs, the protective bacteria can dampen the short- and long-term side effects of the treatment.
Ultimately, the research could potentially lead to new nutritional supplements, probiotics, or technical therapies to help improve colon health in cancer patients. Because chemotherapy-related microbiome changes in children are linked to health complications later in life – including obesity, asthma and diabetes – discovering new strategies to protect the gut is especially important for pediatric cancer patients.
“We were really inspired by bioremediation, which uses microbes to clean up polluted environments,” said Erica Hartmann of Northwestern, senior author on the study. “Usually bioremediation applies to groundwater or soil, but here we have applied it to the intestines. We know that certain bacteria can break down toxic cancer treatments. We wondered if these bacteria, by breaking down drugs, could protect the microbes around them. Our study shows that the answer is ‘yes’. If some bacteria can break down toxins quickly enough, it has a protective effect on the microbial community. “
The research is published today (May 26) in the journal mSphere.
Hartmann is an assistant professor of environmental biology at Northwestern’s McCormick School of Engineering. Ryan Blaustein, a former postdoctoral fellow in Hartmann’s lab, is the lead author of the paper. He is now a postdoctoral fellow at the National Institutes of Health.
While cancer treatments are life-saving, they also cause very serious and painful side effects, including gastrointestinal problems. Chemotherapy, in particular, can destroy the healthy, ‘good’ bacteria in the human gut.
“Chemotherapy drugs don’t differentiate between killing cancer cells and killing microbes,” Hartmann said. “Microbes in your gut help digest your food and keep you healthy. Killing these microbes is especially harmful to children, as there is some evidence that disruption of the gut microbiome at a young age can lead to potential health problems later in life. ”
In collaboration with Dr. Patrick Seed, a professor of pediatrics and microbiology immunology at Northwestern University Feinberg School of Medicine, learned Hartmann’s lab from Raoultella planticola. Raoultella planticola occurs naturally in low amounts in the human gut and can break down the chemotherapy drug doxorubicin, which has been shown in other research.
We were really inspired by bioremediation, which uses microbes to clean up polluted environments. Usually bioremediation applies to groundwater or soil, but here we have applied it to the intestines “
To test whether this degradation effect could protect the entire microbiome, the team developed simplified microbial communities, including several types of bacteria typically found in the human gut. The ‘fake gut communities’ include strains of bacteria (Escherichia coli and Klebsiella pneumoniae) that break down doxorubicin well, strains (Clostridium innocuum and Lactobacillus rhamnosus) that are particularly sensitive to doxorubicin and one strain (Enterococcus faecium) that is resistant to doxorubicin but does not degrade it.
The team then exposed these fake gut communities to doxorubicin and found increased survival in susceptible strains. The researchers concluded that by breaking down doxorubicin, certain bacteria made the drugs less toxic to the rest of the gut.
While the research points to a promising new avenue for the potential protection of cancer patients, Hartmann warns that translating the new findings into treatments is still a long way off.
“There are several potential uses that would be great for helping cancer patients – especially pediatric patients – not experience such serious side effects,” she said. “But we are far from over.”
The study, “Biotransformation of Doxorubicin Promotes Resilience in Simplified Gut Microbial Communities,” was supported by the National Institutes of Health (grant number TL1TR001423).