Colorectal cancer is the third most common cancer and is responsible for approximately 600,000 deaths per year worldwide. Previous evidence has demonstrated an association between antibiotic use and colorectal cancer, which is troubling given rising antibiotic use; however, further research is needed to better understand this association. Authors of a recent report found that antibiotic use increased the risk of proximal colon cancer, but decreased the risk of rectal cancer in females.

Colorectal cancers occur in three zones - the proximal colon, composed of the first two segments of the large intestine; the distal colon, composed of the second two segments of the large intestine; and the rectum. Most colon cancers occur in the proximal colon with distal colon and rectal cancers more common in males and in adults younger than 50 years. More than half of all colorectal cancer cases are attributable to modifiable risk factors such as smoking, diet, alcohol consumption, physical inactivity, and possibly medication.

The gut microbiota is composed of the community of bacteria, archaea, fungi, and viruses that live in the human intestine, and its composition is highly sensitive to changes in lifestyle and use of medications. Antibiotics suppress the growth of beneficial gut bacteria in addition to pathogens, causing long term disruption of the gut ecosystem. Use of antibiotics may result in chronic inflammation and tumorigenesis due to overgrowth of pathogens such as Clostridium difficile; however, additional research is needed to understand the difference between classes of antibiotics and the effects of dose and duration.

The authors collected data regarding colorectal cancer incidence and antibiotic use from the Swedish national population register. They compared data between more than 40,000 participants with colorectal cancer and more than 200,000 participants without colorectal cancer who were matched for age, sex, and home county. The researchers collected additional data about the participants, such as country of origin, socioeconomic status, and healthcare utilization. All data were collected between the years of 2005 and 2016.

Moderate use of antibiotics (defined as use between 11 and 60 days) was associated with a 15 percent increased risk of colorectal cancer compared to no use. Very high use of antibiotics (defined as use greater than 180 days) was associated with a 17 percent increased risk compared to no use. However, these associations were no longer statistically significant when the investigators removed data regarding antibiotic use in the two years prior to cancer diagnosis. They removed this data to account for reverse causation, meaning use of antibiotics for illnesses caused by cancer. Excluding this data, the investigators found that moderate and very-high antibiotic use was significantly associated with proximal colorectal cancer. Surprisingly, antibiotic use decreased the risk of rectal cancer in females. This decreased risk was not present for proximal or distal colon cancers. Finally, the researchers found that the antibiotic classes quinolones, sulfonamides, and trimethoprims were most associated with proximal colon cancer, while nitrofurantoins, macrolides, and lincosamides were protective against rectal cancer.

This large study demonstrates a relationship between increased antibiotic use and higher risk of proximal colon cancer. Surprisingly, some antibiotics may be protective against rectal cancer.

• Link to full publication.
• Learn how to restore a healthy microbiome after taking antibiotics with Tim Ferris in this clip.