Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case–Control Study

Abstract

BackgroundMicrobiotical dysbiosis induced by a Western diet seems to be associated with an increased risk of developing colorectal cancer (CRC). Few other factors with an effect on the colonic microbiota and their association with CRC have been evaluated.AimWe investigated whether the use of antibiotics is associated with CRC risk.MethodsData on the use of antibiotics and comedication were extracted from a health insurance database for subjects with a diagnostic-related group for CRC between 2006 and 2011 and four age- and sex-matched controls. Antibiotic use was categorized according to the number of prescriptions during a 5-year follow-up period (1–6 years prior to CRC). Multivariable conditional binary logistic regression analysis was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for different levels of use.ResultsA total of 4029 cases (47 % male, mean age at diagnosis 71 ± 11 years) and 15,988 controls were included. Antibiotics had been prescribed to 2630 (65.3 %) cases and 10,234 (64.0 %) controls (p = 0.13). An increasing use of antibiotics was associated with an increasing risk of CRC [multivariable OR for high (≥8 prescriptions) vs. no prescriptions: 1.26, 95 % CI 1.11–1.44, p-trend <0.01]. For each increase of 5 prescriptions, the OR for CRC was 1.05 (95 % CI 1.01–1.09).ConclusionWe found an association between the use of antibiotics, especially when used frequently, and the risk of developing CRC. Further studies are needed to establish under which conditions the use of antibiotics increases the risk of developing CRC.

Fecal microbiota transplantation in cancer management: Current status and perspectives

“…37,38 The fecal microbiota from patients with CRC promoted tumorigenesis in germ-free or conventional mice given a carcinogen, 39 which showed the carcinogenic properties of the CRC microbiota. Accumulating epidemiological evidence supports the opinion that long-term antibiotic exposures, known to change the composition and decrease the diversity of gut microbiota, 40 increase the risk of CRC, [41][42][43][44] as well as gastric, pancreatic, lung, breast and prostate cancers. 45 Consistent with this, long-term antibiotic use was highly correlated with increased colorectal tumor progression in the Apc Min/+ mouse, a genetic model for human adenomatous polyposis.…”

Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut Barrier and Triggers Colitis

“…Because a substantial fraction of ABx-treated patients shows an analogous rise in PA, it is highly probable that ABx treatment is not only associated 28 but indeed an independent risk factor for the development of chronic intestinal inflammation in IBD-susceptible individuals. It may be speculated that the high PA-mediated impairment of the large intestinal barrier might also play a role in the development of other chronic diseases that have been found to be associated with ABx therapies, such as irritable bowel syndrome22, 23 or colorectal cancer 25, 26. However, the pathophysiological impact of the rise in PA on the intestinal barrier in ABx-treated patients remains to be elucidated.…”

Effects of Antibiotics on Gut Microbiota

“…A reduced abundance of these species might be a consequence of post-antibiotic dysbiosis. Supporting this assumption, a recent case-control study demonstrated an association between frequent use of antibiotics and the risk of CRC [81]. A cohort study including more than 3 million people could also demonstrate a relative risk of 1.37 (95% CI 1.34-1.40) of developing cancer and a risk of 1.15 (95% CI 1.04-1.26) of developing CRC in people who have had 6 antibiotic prescriptions or more in comparison to people with one prescription or less within the past 3 years [82].…”