Study suggests sugar-rich foods amplify antibiotic disruption of the gut microbiome
Chris Dall, MA44 minutes ago.
Antimicrobial Stewardship
A spoonful of sugar may help the medicine go down, as Mary Poppins sang. But for blood cancer patients on antibiotics, it could make things worse.
That’s according to a five-year study that closely tracked the role that diet plays in antibiotic-induced disruption of the gut microbiome. The findings were published last week in Nature.
The observational study, led by researchers with New York University Langone Health, Memorial Sloan Kettering Cancer Center, and City of Hope National Medical Center, followed blood cancer patients during hospitalization before and after stem cell transplantation. Because chemotherapy saps the immune system, cancer patients are highly vulnerable to infections and rely on antibiotics to help fight them off.
All of the patients in the study were on antibiotics at one point during the study, and many received broad-spectrum antibiotics, which are known to significantly disrupt the balance of good and bad bacteria in the gut microbiome and can leave people more susceptible to drug-resistant infections.
What the researchers were investigating is how much a person’s diet, which has also been shown to shape the gut microbiome, contributes to this effect.
In one of the largest and most detailed studies of its kind, the researchers tracked 9,419 meals eaten by 173 blood cancer patients from 2017 through 2022 down to the gram, asking them after every single meal about the amount they consumed and pairing those data with nutritional information on each meal. They then analyzed patient stool samples to monitor changes in the gut microbiome.
“The microbiome is extremely important for our health,” co-senior study author Jonas Schluter, PhD, an assistant professor in the Department of Microbiology at NYU Langone, told CIDRAP News. But it’s even more important for cancer patients undergoing stem cell transplantation, as research has shown that microbiome disruption in these patients is associated with poor prognosis.
“In these patients, there are strong associations over decades now whereby the outcome of the cancer therapy is associated with the state of the microbiome during the cancer therapy,” he said. “It therefore makes sense to study in these patients what one could do about the microbiome.”
Intake of sweets amplifies exacerbates the microbiome injury
What Schluter and his colleagues found was that intake of sweets, sugars, and beverages (collectively referred to in the study as sweets) by patients in the study magnified what Schluter calls the “microbiome injury” caused by antibiotics. Analyzing data from 1,009 stool samples and 158 patients, they learned that, for every 100-gram increase in intake of sweets after antibiotic exposure, there was an additional 24% decrease in alpha diversity, which captures the number of different bacterial species and how evenly distributed they are in the microbiome.“The sugars exacerbate the already established diversity loss that antibiotics can cause,” Schluter said. Several layers of analysis returned similar results.
Further analysis suggested formulated nutritional beverages, such as sports drinks and nutritional shakes, were key contributors to bacterial diversity loss, as opposed to naturally occurring sugars. The study authors note that these nutritional supplements are commonly recommended to transplant recipients.
One particular bacterial species that appeared to benefit from the reduced bacterial diversity was Enterococcus faecium, an opportunistic pathogen that is a leading cause of hospital-associated infections. It’s often drug-resistant and can be especially devastating for cancer patients, particularly if it gets into the bloodstream.
As Schluter explained, the simple sugars “feed the surviving bacteria, which exacerbates the damage to the antibiotics have done because often the surviving bacteria are not the ones we really want to see there.”
Schluter noted that one of the antibiotics that E faecium is naturally resistant to is vancomycin, which several patients were taking to ward off Clostridioides difficile infection. The researchers also found that among those who had a higher intake of sugar, the duration of broad-spectrum antibiotic exposure was associated with a higher mortality risk.
“Now that we know that sugars make this perhaps unavoidable dynamic worse, it begs the question: Can we not do something about it with dietary changes?” he asked.
Additional experiments in mice who were given antibiotics and a high-sucrose diet corroborated the findings; the mice saw a 16-fold increase in the Enterococcus population in their gut microbiome by day three of the study, and 33-fold increase by day six. When the mice were fed the high-sucrose diet without antibiotics, there was no effect.
“The fact that animal studies support associations we found in patient data provides a compelling rationale for future clinical trials to evaluate whether reducing sugar intake during antibiotic use would protect the microbiome,” co-senior study author and City of Hope president Marcel van den Brink, MD, PhD, said in a press release.
Mitigating the collateral damage of antibiotics
Martin Blaser, MD, who directs the Center for Advanced Biotechnology and Medicine at Rutgers University and has been studying the human microbiome for decades, said the findings could be potentially significant for oncology.“We know that antibiotics, by perturbing the microbiome, interfere with the efficacy of some important therapeutic regimens, particularly involving immunotherapy,” said Blaser, who was not involved in the study. “Sugar can be seen as a second hit: We know that sugar disrupts the microbiome, and this study shows the synergistic effect of the two perturbers.”
Schluter said cancer patients are a good population for studying this effect, because it’s so amplified in them, “like a magnifying glass into the effects that food can have.” But while he cautions that more research is needed to establish causality and understand the mechanisms at work, he believes the findings could have implications for otherwise healthy people who need to take antibiotics. Taking in fewer sweets while on antibiotics, he said, is something that he would practice.
“It is now clearer and clearer that even in otherwise healthy people, if you take oral antibiotics, there are collateral damages to the microbiome that have health consequences,” Schluter said. “So what can we do to mitigate that damage?”