Dietary Sucrose Exacerbates Antibiotic-Induced Microbiome Injury in Allo-HCT

Patients with blood cancers who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are typically hospitalized for several weeks while they receive chemotherapy, sometimes irradiation, and antibiotics. Nutrition influences the composition of the gut microbiome, yet its contribution to microbiome disruption during cancer treatment remains poorly understood. We profiled fecal microbiome composition and detailed dietary intake in 158 allo-HCT patients. Intake of sugar-enriched foods during antibiotic exposure predicted low fecal microbiome α-diversity and expansion of Enterococcus, two patterns of microbiome we previously identified as predictors of mortality in this population.

To validate this finding, we developed a simple mouse model of antibiotic-induced expansion of Enterococci endogenous to the mouse gut microbiome by administering a single subcutaneous dose of the carbapenem antibiotic biapenem to C57BL/6 mice induced a moderate bloom of Enterococci, as assessed by dilution plating on selective agar. In line with our observations in human patients, supplementation of the disaccharide sucrose to the diet intensified the Enterococcus expansion, leading to a 51.8-fold median increase at day 3 (p = 0.002) and a 42.4-fold median increase at day 6 (p = 0.030). Importantly, sucrose alone, without antibiotics, did not influence the abundance of Enterococcus.

The monosaccharide components of sucrose, fructose and glucose, were each sufficient to exacerbate the antibiotic-induced Enterococcus bloom (fructose median fold change on day 3: 104.7, p = 0.002; glucose median fold change on day 3: 105.1, p = 0.003), although the effect was not as sustained as that of sucrose, as by day 6, no significant differences were observed in colony counts between fructose- and glucose-treated samples and diet vehicle-treated samples. A similar pattern was observed in mice that were irradiated and allografted with T-cell-depleted grafts to model the early post-transplant period: a bloom of Enterococcus induced rapidly by the carbapenem that resolved 5 days later, and sucrose prolonged the relative expansion. These findings underscore the influence of diet on gut microbiota diversity and composition in HCT patients receiving antibiotics, highlighting the need for targeted nutritional interventions to mitigate adverse microbiome-related outcomes in this vulnerable population. Avoiding sugar-enriched foods while taking antibiotics may also have relevance outside the setting of cancer treatment. The general recommendation to limit consumption of sweets for cardiovascular health might, with further study, be tailored to abbreviated periods of avoidance to mitigate microbiome disruption during antimicrobial therapy.

Schluter:Jona Health Inc: Current equity holder in private company, Current holder of stock options in a privately-held company; Postbiotics Plus LLC: Current equity holder in private company. Peled:Canaccord Genuity, Inc: Consultancy; CSL Behring: Consultancy; Postbiotics Plus Research: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; DaVolterra: Consultancy; Crestone Inc: Consultancy; MaaT Pharma: Consultancy; Seres Therapeutics: Patents & Royalties, Research Funding; Prodigy Biosciences: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Perales:Novartis: Research Funding; OrcaBio: Current equity holder in private company; Incyte: Research Funding; Allogene: Research Funding; Miltenyi: Research Funding; Kite/Gilead: Research Funding; Nektar: Research Funding; Biotec: Research Funding; Omeros: Current Employment, Current equity holder in publicly-traded company; NexImmune: Current Employment, Current equity holder in publicly-traded company.