Sulfur Microbial Diet May Lead to Adenomas, Early-Onset CRC

neoplasm, colorectal neoplasia, adenoma
Investigators aimed to determine whether diet-induced changes to specific gut microbial populations may lead to the development of early-onset CRC.

In adults, and possibly adolescents, long-term adherence to diets that increase sulfur-metabolizing bacteria may lead to an increased risk of developing early-onset conventional adenomas, according to study results published in Gastroenterology. The risk for conventional adenomas, a surrogate endpoint for colorectal cancer (CRC), is not associated with diagnosis after age 50 but may be greater in those with an advanced histology or greater malignant potential.

In the United States, the incidence of CRC among people aged 20 to 49 years has increased. It is believed that diet may play a role in this increase among younger adults and that microbial metabolism of sulfur, which produces hydrogen sulfide, may contribute to this; however, hydrogen sulfide, a gastrointestinal carcinogen, cannot be measured easily at scale, leading to a gap in supporting evidence of its role in early neoplasia.

A team of researchers conducted a prospective investigation on a cohort of young women to determine whether diet-induced changes to specific gut microbial populations may lead to the development of early-onset CRC. They evaluated long-term adherence to sulfur a microbial diet, which was identified by a high intake of processed meats and a low intake of mixed vegetables and legumes.

The primary endpoint was the diagnosis of colorectal adenomas or serrated polyps in patients aged less than 50 years. Sulfur microbial diet scores were grouped into quartiles, as were adjustments for caloric intake. A secondary analysis among patients who were aged 50 years and older was performed to assess whether a sulfur microbial diet was also linked to an increased risk for older-onset adenomas.

Among the 30,818 women aged less than 50 years at the time of their lower endoscopy, women who adhered more closely to a sulfur microbial diet were more likely to have a higher body mass index (BMI), more likely to have ever smoked, less likely to exercise frequently, more likely to use nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and were less likely to use multivitamins.

A total of 2911 cases of early-onset colorectal neoplasia were documented by the investigators from 45,843 lower endoscopies. Of these cases, 1242 were conventional adenomas, 1669 were serrated lesions, 230 were polyps with advanced histology, and 200 were 1 cm or larger in size.

Compared with women in the lowest quartile (Q1, lowest sulfur microbial diet score), women in the highest quartile (Q4, highest sulfur microbial diet score) had an increased risk for early-onset conventional adenomas, even after adjustments for putative CRC risk factors were made (Ptrend =.02); however, there was no association between a sulfur microbial diet and serrated lesions (Ptrend =.08). Among patients who were aged 50 years or older with conventional adenomas, no clear relationship to a sulfur microbial diet was noted.

Among patients who had an advanced histology and, therefore, greater malignant potential, there seemed to be a positive association with early-onset conventional adenomas among women in Q4 compared with women in Q1. This trend was especially prevalent in adenomas characterized by tubulovillous or villous histology (odds ratio [OR] of Q4 vs Q1, 1.65; Ptrend =.04) compared with tubular adenomas (OR, 1.24; Ptrend =.09). Although a strong trend was also observed towards increased risk for polyps larger than 1 cm, this was not statistically significant (OR, 1.34; Ptrend =.06).

Neoplasia starting in the proximal colon was found to drive the increase in the risk for conventional adenomas due to a sulfur microbial diet (OR, 1.58; Ptrend =.01); however, this relationship was not clear in serrated lesions.

Investigators acknowledge a number of limitations, including the possibility of residual confounding due to the study’s observational nature. Additionally, the study population included only women within a certain age group, limiting its generalizability among men and those within other age groups.  

“Epidemiologic validation or further mechanistic work are needed to determine the underlying biology that explains observed heterogeneity in the anatomic location and histopathology of sulfur-induced CRC precursor lesions,” the investigators wrote. “How other gut microbial determinants, including body composition and other lifestyle factors (e.g., physical activity and medications), may influence the link between diet-induced enrichment of carcinogenic microbes, whether dietary modification can modulate long-term carriage of harmful gut bacteria, and how these complex interactions may culminate in a viable disease prevention strategy remains to be determined,” they concluded.

Reference

Nguyen LH, Cao Y, Hur J, et al. The sulfur microbial diet is associated with increased risk of early-onset colorectal cancer precursors. Gastroenterol. Published online July 14, 2021. doi:10.1053/j.gastro.2021.07.008