Eating sweets while taking antibiotics may worsen the harm done by the drugs to the normal community of bacteria in the gut, a new study has found. The study of hospitalized cancer patients found an additional 21% reduction in the variety of helpful bacterial species present, for every 100 grams of sugar consumed in the 48 hours before treatment.
The work centers on the intestinal microbiome, which harbors bacterial species that co-evolved with humans to live in the digestive tract, help digest food, and support the immune system. Antibiotics, among the most prescribed drugs globally, are known to eliminate helpful bacteria alongside harmful species, in some cases letting harmful ones dominate.
The microbiome is more capable of resisting the buildup of harmful pathogens when natural species diversity is in place, but antibiotics reduce diversity in ways that make the gut more vulnerable to disease, the study authors said.
Led by researchers from NYU Langone Health, City of Hope, and Memorial Sloan Kettering, the study precisely tracked every food item in 9,419 meals eaten by 173 hospitalized cancer patients and then measured their gut microbiome changes. The team found an additional 21% reduction in alpha diversity, a measure of the variety of helpful bacterial species present, for every 100 grams of sugar consumed in the 48 hours before treatment.
Bacterial blooms
Publishing online Sept. 30 in the journal Nature, the work also showed how the combination of a sugary diet and antibiotic treatment caused blooms in patients of the bacterial species Enterococcus faecium, which has been linked to hard-to-treat infections. Experiments in mice confirmed this pattern, wherein exposure to the antibiotic biapenem and dietary sucrose drove a 16.3-fold increase in the Enterococcus population in the gut by day 3 of the study, and 33.4-fold higher burden by day 6.
“No matter how we analyzed the data, the same strong signal kept appearing,” observed co-senior study author Marcel van den Brink, MD, PhD, chief physician executive at City of Hope. “The patients who consumed more sweets while taking antibiotics were more likely to experience a loss of microbiome diversity as aggressive microbes crowded out other strains of bacteria.”
One organism stood out: Enterococcus. When it takes over the microbiome, patients undergoing transplant face a higher risk of bloodstream infections, graft-versus-host disease and other life-threatening complications.
Multiplying injury
The combination of high-sugar foods and broad-spectrum antibiotics appeared to multiply injury to the microbiome, leading to a substantial 24% drop in bacterial diversity for every 100-gram increase in sweets (equivalent in sugar content to a large milkshake).
“As we are learning how collateral damage of antibiotics to the microbiome are linked with long-term health problems, it’s important to identify factors that limit these unintended health risks,” said the study’s co-senior author Jonas Schluter, PhD, assistant professor in the Department of Microbiology at NYU Langone. “Our study, which used more than 9,000 recorded meals, suggests that modifying diet during and after antibiotics, specifically by reducing sweets intake, could help with that.”
The research team studied patients with blood cancers because they receive antibiotics frequently and precisely tracking food intake is feasible during hospitalization. The researchers recorded patient diets at every meal and collected microbiome samples daily, making the study among the largest and highest-resolution of its kind to date.
Cancer care factor
“The microbiome is emerging as an important factor in cancer care,” said Dr van den Brink. “For patients undergoing intensive treatments such as bone marrow transplantation, the healthy diversity of the gut microbiome can have important implications for outcomes. Studies like this help us better understand how everyday factors, including diet, may affect a delicate balance that influences how patients respond to treatment, recover and experience side effects.”
Patients with blood cancers who undergo stem cell transplantation are typically hospitalized for several weeks, during which they receive both chemotherapy and antibiotics. During this time, they show drastic changes in nutrition as well as severe damage to their microbiomes. In these patients, harmful bacterial species like Enterococcus faecium often thrive because the rest of the gut ecosystem has been “destroyed.”
“Especially in blood cancer patients, microbiome injury is associated with worse outcomes, including higher overall mortality and infections,” said Jonathan Peled, co-senior author on the study and associate director of the Center for Hematological Malignancies at Memorial Sloan Kettering Cancer Center. “An important next step will be to design clinical trials to test whether short-term dietary changes can improve clinical outcomes in patients.”
Tested in mice
The researchers also tested their hypothesis that sugar exacerbates microbiome injury by giving broad-spectrum antibiotics to healthy mice and feeding them a variety of diets. Mice that ate a high-sucrose diet quickly developed an overgrowth of Enterococcus in their guts. Mice that ate the high-sugar diet without antibiotics, however, maintained normal bacterial diversity.
“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,” said Dr. van den Brink, the Deana and Steve Campbell Physician Executive Distinguished Chair and the Morgan and Helen Chu Presidential Chair.
“The microbiome is emerging as an important factor in cancer care,” Dr. van den Brink said. “The better we understand what supports and disrupts it, the more opportunities we have to reduce treatment side effects while improving how patients respond to and recover from therapy.”
Supporting cancer patients
For cancer patients, he noted, the study results reinforce diet as a strong influence on the microbiome and as one of the most practical ways hospitals can support recovery during treatment.
“Many of the foods and drinks we encourage hospitalized patients to consume, like nutritional shakes, smoothies and sports drinks, are high in sugar content,” Dr. van den Brink said. “That’s something we’ll need to evaluate when prescribing antibiotics.”
The practical takeaway for physicians, he says, is that antibiotic stewardship matters beyond preventing antibiotic resistance.
Antibiotic stewardship
“Antibiotic stewardship includes thinking about how different antibiotics affect the microbiome,” Dr. van den Brink said. “Our study demonstrates that some antibiotics disrupt beneficial gut bacteria more than others.”
To preserve microbiome health, he encourages patients to ask their healthcare team to ensure antibiotics are thoughtfully chosen from equally effective treatment options for controlling infections.
So, should people cut out sugar while taking antibiotics?
“It’s premature to recommend everyone taking antibiotics avoid sugar,” Dr. van den Brink said. “On the other hand, we don’t have strong evidence that probiotics help preserve or restore microbiome diversity and many people choose to take them anyway. There’s no harm in limiting sugar in your diet, and it’s an easy thing to try.”
Sugars amplifying disruption
“The new work identifies dietary sugars as an amplifier of antibiotic-induced microbiome disruption, probably because the potentially harmful bacteria that survive the antibiotics are benefiting from the dietary sugars that they can use to expand,” said study second author William Jogia, a PhD student in Dr. Schluter’s lab in the Institute for Systems Genetics. “While the findings suggest that reducing simple sugars may limit microbiome injury, whether sugar directly supports Enterococcus, weakens competing bacteria, or acts through another mechanism in patients remains to be seen.”
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Along with Drs. Schluter and Jogia, study authors from the Schluter lab at the Department of Microbiology and Institute for Systems Genetics at NYU Langone Health were Caichen Duan, Chenzhen Zhang, Fanny Matheis, and Alexis Sullivan.
Authors from the Adult Bone Marrow Transplantation Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center were co-senior author Jonathan Peled, co-first authors Anqi Dai and Annamaria Ballweg, along with Madhumitha Rangesa, Peter Adintori, Mirae Baichoo, Nicholas Waters, Abrielle Swartz, Sukanya Sahu, Brianna Gipson, Sandeep Raj, Zoe Pierce, Kenton Wu, Justin Neuberger, Adam Warren, Marissa Lubin Buchan, Ana Gradissimo, Luigi Amoretti, Annelie Clurman, Daniel Brereton, Paul Giardina, Miguel-Angel Perales, and Sergio Giralt. Also authors from Memorial Sloan Kettering Cancer Center were Teng Fei in the Department of Epidemiology and Biostatistics, Oriana Miltiadous in the Department of Pediatrics, Tatanisha Peets in Food and Nutrition Services, and Marina Burgos da Silva in the Human Oncology & Pathogenesis Program.
Other authors were Tyler Funnell, Natalie Smith, John Slingerland, Antonio Gomes, and Robert Jenq in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope National Medical Center in Los Angeles; Eiko Hayase in the Departments of Genomic Medicine and Stem Cell Transplantation Cellular Therapy in the Division of Cancer Medicine at University of Texas MD Anderson Cancer Center; Corrado Zuanelli Brambilla in the Hematology Unit, Department of Cellular Therapy, Hematology and Laboratory Medicine at Azienda Ospedaliera Universitaria Senese in Siena, Italy; Abigail Johnson in the Division of Epidemiology and Community Health in the School of Public Health at the University of Minnesota, Minneapolis; Dan Knights in Department of Computer Science and Engineering at the University of Minnesota; and Kate Markey in the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center in Seattle.
Funding for the study was by National Institutes of Health grants K08HL143189, P30 CA008748, P01CA023766, R35CA284024, DP2AI164318, R01CA269617, P30CA0160087, R01-CA228358, R01-CA228308, F31-CA261086, P30 CA008748, P01-CA023766; R01-HL123340, R01-HL147584, and P01-AG052359. Other support came from the Gabrielle’s Angel Foundation, a Helen Hay Whitney postdoctoral fellowship, the Starr Cancer Consortium, The Tri-Institutional Stem Cell Initiative, the Lymphoma Foundation, the Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival, the Parker Institute for Cancer Immunotherapy, the American Society of Clinical Oncology Young Investigator Award, a Hyundai Hope on Wheels Young Investigator Award, a Tow Center for Developmental Oncology Career Development Award, and an AIRC fellowship for Abroad.
Dr. Schluter has filed intellectual property applications related to the microbiome (reference numbers #63/299,607), serves on an advisory board and holds equity in Jona Health, and is cofounder of Postbiotics Plus Research. These relationships are being managed in keeping with the policies of NYU Langone Health.
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