Sulfur-metabolizing Bacteria Linked to Increased Risk of Colorectal Cancer

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Most cases of colorectal cancer (CRC) are diagnosed in patients without a clear genetic predisposition. Determining whether the disease can be prevented through changes in lifestyle (such as dietary intake) is a high research priority.

Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide, have been associated with the development of CRC in animals. Now, Long H. Nguyen, MD, instructor in the Division of Gastroenterology at Massachusetts General Hospital, Andrew T. Chan, MD, MPH, director for cancer epidemiology in the Mass General Cancer Center, chief of the Clinical and Translational Epidemiology Unit in the Department of Medicine and vice chief for clinical research in the Division of Gastroenterology, and colleagues have demonstrated on a population scale that a diet high in sulfur-metabolizing bacteria is associated with increased risk of CRC. Their report appears in Gastroenterology.

Study Details

The researchers used data from the Health Professionals Follow-up Study (HPFS), an ongoing prospective cohort study of U.S. male health care professionals who were 40 to 75 years old at enrollment in 1986. Every two years, the participants complete questionnaires about medical problems and lifestyle; every four years, they complete a food frequency questionnaire.

Nested within the HPFS is the Men's Lifestyle Validation Study (MLVS) of generally healthy participants. The team designed a novel two-stage study strategy: (1) use the MLVS to develop a sulfur microbial diet score and (2) use the larger HPFS as a prospective testing cohort to evaluate any link between the diet score and risk of new-onset CRC.

Developmental Cohort

The researchers asked 307 participants in the MLVS to provide two stool samples, six months apart. By analyzing the DNA and RNA of 925 samples, they identified 43 sulfur-metabolizing bacterial species. Using information from the food questionnaires, they determined which foods and drinks were most predictive of those species:

• Processed meat
• Liquor
• Artificially sweetened low-calorie drinks

Foods negatively associated with sulfur-metabolizing species were beer, fruit juice, legumes, vegetables and sweets/desserts.

Testing Cohort

The team then calculated sulfur microbial diet scores for each of 48,246 men in the HPFS, based on food questionnaire data from 1986 to 2010, and followed them until January 31, 2012. They found that, compared with men whose sulfur microbial diet score was in the first quartile, those in the highest quartile had a 43% greater risk of distal colon and rectal cancer (RR, 1.43; 95% CI, 1.13–1.81; P=.002) after adjustment for traditional risk factors.

No clear association was observed between diet score and proximal CRC.

The association between diet score and CRC was especially strong among men with no family history of CRC, lower body mass index and/or no prior history of smoking.

Future Gastroenterology Research

It's already known that intake of certain foods, such as processed meats, can contribute to the risk of CRC. What's new from this study is evidence that these food–cancer relationships may exist because dietary factors modify the gut microbiome by enriching for carcinogenic bacteria.

Alteration of gut microbial communities through diet might one day be proven to reduce the risk of an array of gastrointestinal diseases, including inflammatory bowel disease.

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