Diet influences susceptibility of intestinal microbiome to antibiotics

A new study has shown that antibiotics alter the type of bacteria present in the mouse's intestine as well as its metabolism. However, diet can exacerbate these changes.

Antibiotics save countless lives each year from harmful bacterial infections – but the community of beneficial bacteria that live in the human intestines, called the microbiome, often suffers collateral damage.

Peter Belenky, assistant professor of molecular microbiology and immunology at Brown University, is studying ways to minimize this side effect, which can lead to C. diff infections and other microbiome imbalances involving the life threatening. In a new study published Thursday, Sept. 12, 2019 in Cell Metabolism, Belenky and his colleagues found that antibiotics alter the composition and metabolism of the gut microbiome in mice and that feeding a mouse can reduce or exacerbate these changes .

The results are a step, says Belenky, to help humans better tolerate antibiotic treatments.

"Doctors now know that each prescription for antibiotics can have adverse health consequences related to the microbiome, but they do not have reliable tools to protect this critical community while also treating life-threatening infections," said Belenky. "The goal of my lab is to identify new ways to protect the microbiome, which could alleviate some of the worst side effects of antibiotics."

The intestinal microbiome is an ecosystem comprising billions of bacteria that have specifically evolved with its host. This community helps the host in many ways, such as breaking down dietary fiber and maintaining overall intestinal health – by ensuring that intestinal cells form a tight barrier and compete for resources with nutrients. harmful bacteria, said Belenky.

The lead author of the study, Damien Cabral, a PhD student in Brown's pathobiology program, treated three groups of mice with different antibiotics and then followed the evolution of the bacteria's composition in the intestines of the mouse and its metabolic adaptation after antibiotic treatment.

Amoxicillin, commonly used to treat ear infections and strep throat, has significantly reduced the types of bacteria present in the intestine and modified the genes used by the remaining bacteria. The researchers also studied ciprofloxacin, used to treat urinary tract infections and typhoid fever, and doxycycline, often used in the treatment of Lyme disease and sinus infections. The changes associated with these medications were less pronounced.

One type of potentially beneficial bacterium common in the human gut, Bacteroides thetaiotaomicron, actually bloomed after treatment with amoxicillin. After treatment, this bacterium is increasingly using enzymes that digest the fiber, a change that seems both to allow it to flourish in the new ecosystem and to protect it in one way or another. antibiotic, explained Belenky.

In general, bacteria have decreased the use of genes involved in normal growth, such as the manufacture of new proteins and DNA. At the same time, they have also increased the use of genes essential to stress resistance.

Interestingly, Belenky's team found that adding glucose to a mouse diet – usually high in fiber and low in simple sugars – increased the sensitivity of Bacteroides thetaiotaomicron to amoxicillin. This suggests that the diet can protect some beneficial intestinal bacteria from the ravages of antibiotics.

"We have known for a long time that antibiotics have an impact on the microbiome," said Belenky. "We also know that diet affects the microbiome. This is the first document that brings together these two facts.

Belenky warned that the study had been conducted on rodents and that there was still much to learn about the interaction between the host diet, microbiome metabolism and vulnerability to different antibiotics.

"Now that we know that nutrition is important for bacterial antibiotic sensitivity, we can ask new questions about the nutrients that are impacting and see if we can predict the influence of different diets," he said. he declared.

Belenky's team is studying the impact of different types of dietary fiber on microbiome evolution after antibiotic treatment, as well as the impact of diabetes on the metabolic environment and antimicrobial susceptibility of the microbiome.

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In addition to Belenky and Cabral, Brown's other writers include Swathi Penumutchu, Elizabeth Reinhart, Benjamin Korry, Jenna Wurster, Rachael Nilson, August Guang, William Sano, and Aislinn Rowan-Nash. Other writers on paper include Cheng Zhang and Hu Li from the Mayo Clinic.

The Ministry of Defense (W81XWH-18-1-0198), the National Science Foundation (1644760) and the COBRE National Institutes of Health (P20GM121344 and P20GM109035) supported the research.

Reference: "Microbial Metabolism Modulates Antibiotic Susceptibility in the Murine Gut Microbiome" by Damien J. Cabral, Swathi Penumutchu, Elizabeth M. Reinhart, Zhang Cheng, Benjamin J. Korry, Jenna I. Wurster, Rachael Nilson , August Guang and William H. Sano, Aislinn Rowan-Nash D., Hu Li and Peter Belenky, September 12, 2019, Cell metabolism.
DOI: 10.1016 / j.cmet.2019.08.020