Oral antibiotic use was associated with a higher risk of early-onset colorectal adenoma (EOCRA) in a large US population, with increasing exposure and longer intervals since use linked to greater risk, according to a nested case-control study of nearly 24,000 patients.
“In recent decades, there has been a striking increase in colorectal cancer (CRC) incidence in young adults <50 years of age, both in the US as well as globally,” the study’s lead researcher, Amanat Bal, MD, MS, of Kaiser Permanente San Francisco Medical Center, said in advance of Digestive Disease Week® (DDW) 2026, where the work was presented. “While multiple mechanisms have been proposed to help explain this, one hypothesis is that gut microflora perturbations could be influencing the colorectal adenoma-to-cancer pathway.”
A wealth of published evidence has shown that antibiotics can disturb the normal bacteria living in the colon and rectum, she continued. When this balance is upset, harmful bacteria can grow more easily, which may increase the risk of tumors forming. “Prior studies have examined the link between antibiotic use and colorectal cancer, as well as antibiotic use and colorectal adenomas in older adults but not specifically among young adults,” Dr. Bal said. “Our study extends prior findings by exclusively examining EOCRA incidence and antibiotic use in adults under 50 years of age.”
Using Kaiser Permanente Northern California patient data, Dr. Bal, senior author Jeffrey K. Lee, MD, MPH, also of Kaiser Permanente, and colleagues evaluated the association between antibiotic exposure and EOCRA in 6,936 patients with EOCRA and 16,900 matched controls with normal colonoscopy findings from 2006 to 2023. EOCRA cases were comparable to their matched controls, with a mean age of 45 years across both groups, 52% female, and similar distributions of race and ethnicity, duration of drug benefits (≥10 years), and colonoscopy date.
The investigators defined antibiotic exposure as oral use at least two years before the index date. In unadjusted analysis, antibiotic exposure was associated with 1.59 times the odds of EOCRA; after adjustment for confounders using conditional logistic regression, the odds were 1.45 times higher.
Risk was elevated across antibiotic types. Broad-spectrum agents were associated with 1.38 times the odds of EOCRA, while narrow-spectrum agents were associated with 1.16 times the odds. “We observed a particularly robust association with sulfonamide and trimethoprim use,” Dr. Bal noted. “Recent studies have suggested that exposure to long-acting sulfonamides in utero may be linked to subsequent CRC in adult offspring, and our findings suggest at a possible mechanistic link tying sulfonamide antibiotic use to a higher risk of adenoma and subsequent carcinoma development.”
The researchers observed a dose-response relationship, with EOCRA risk rising with the number of antibiotic dispensations and peaking at seven to nine courses (1.60 times the odds vs no exposure).
Timing of exposure also influenced risk. The association strengthened as the interval since antibiotic use increased, with the highest risk observed five to less-than-eight years after exposure, corresponding to 1.71 times the odds of EOCRA.
Although causality cannot be established from this observational study, Dr. Bal concluded that the overall findings support the hypothesis that antibiotic exposure may contribute to the development of EOCRA and underscore the need for judicious antibiotic use in clinical practice. “We also observed a modest dose-response relationship, in which increasing antibiotic prescription burden was associated with increased EOCRA risk, which suggests that cumulative antibiotic exposure may be an important factor to take into account when engaged in clinical care,” she said.
Dr. Bal reported having no disclosures.
DDW is AGA’s annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.