A recent study by Professor Ma Yanlei and his team, scholars from the Colorectal Surgery Department of Fudan University Shanghai Cancer Center (FUSCC), has reported for the first time that significant differences exist between early-onset colorectal cancer (EO-CRC, in adults aged under 50 years) and late-onset colorectal cancer (LO-CRC, in adults aged 50 and older) in terms of the changes in gut microbiome, metabolites, and microbial enzyme genes. This research team has also developed a diagnosis model based on “gut microbiome-metabolites-microbial enzyme genes” combined markers. With this model, it is expected to achieve early screening and precise detection of high-risk populations and patients of EO-CRC through fecal samples in the future, further promoting the transformation and application of microbiome-based diagnostic strategies in frontline clinical practice.
This exploratory research provides a new perspective and direction for understanding the pathogenesis of EO-CRC and exploring suitable methods for its early screening and diagnosis. The relevant findings have recently been published in Gut, a leading international journal in gastroenterology.
Colorectal cancer is one of the most common digestive tract malignancies and is generally regarded as a senile disease. However, its incidence rate has shown a significant younger trend in recent years. As estimated by the National Cancer Institute, the U.S., the incidence rate of EO-CRC will double in the next 15 years, with 20% of colorectal cancer affecting people under the age of 50 years, if the current trend continues.
In 2013, community-based colorectal cancer screening was first included in Shanghai’s Public Health Service Program, but this service mainly targets the elderly. Generally, the detection of EO-CRC is associated with late consultation when symptoms already occur, such as changes in bowel habits, hematochezia, diarrhea, alternating diarrhea and constipation and local abdominal pain. Therefore, the best “window period” for early diagnosis is often missed.
“Enteroscopy is an effective tool for colorectal cancer detection, but its extensive use in young adults for early screening may not necessarily achieve a favorable benefit-risk balance as over diagnosis may impose an unnecessary economic burden on individuals.” Current studies on the clinical diagnosis of EO-CRC have focused on exploring and developing better risk prediction tools to assist in early identification of high-risk populations, as well as establishing better screening strategies.
Gut microbiome constitutes an important micro-environment closely related to human intestinal health. Evidence is accumulating that microecological disorders in the intestines are the key environmental factors to the occurrence and development of colorectal cancer, and that the gut microbiome of the elderly is significantly different from that of the young. Are there any characteristic pathogens and metabolites of diagnostic significance in EO-CRC patients? Are these microbiome and metabolites important pathogenic factors predisposing to the development of EO-CRC?
To address these unsolved problems, Prof. Ma with his team conducted fecal metagenomic and metabolomic sequencing analysis on Chinese patients with EO-CRC, LO-CRC and age-matched healthy controls (n = 549 in total) over a four-year period and further created a random forest model for EO-CRC identification based on multi-omics markers.
For the first time worldwide, the research team has characterized the gut microbiome and metabolites of Chinese EO-CRC patients based on large-sample cohorts. According to Prof. Ma, EO-CRC appears with serious imbalance of gut microbiome and significantly decreased fecal microbial diversity, as well as the significant difference from LO-CRC in terms of gut microbiome and metabolites.