With colorectal cancer rates steadily increasing among people under 50 scientists at the University of Illinois Urbana-Champaign are delving into the role of the gut’s smallest inhabitants the complex community of microbes to uncover potential causes and pave the way for new treatments. In a recent study the team used genetically modified mice lacking a critical immune-regulating gene a mutation often seen in early-onset colorectal cancer patients to recreate conditions similar to those experienced by individuals at high risk for early-onset colitis a chronic inflammation of the colon that frequently precedes cancer. Their investigation focused on how changes in the gut microbiome and the metabolites produced by these microbes interact with gene signaling pathways to influence disease progression. The researchers found that when the genetically altered mice were subjected to stress they developed more severe inflammation driven by dysbiosis a disruption of the normal microbial balance which allowed harmful bacteria to thrive while beneficial ones were crowded out. These problematic microbes in turn, produced harmful metabolites that further aggravated the colon, in contrast to the protective compounds generated by a healthy microbiome. By comparing the microbiome composition and metabolite profiles of these mice with those of healthy controls the team mapped how microbial imbalances and stress-related metabolic changes can amplify inflammation and significantly elevate the risk of early-onset colorectal cancer.

Inflammation in the colon creates conditions that favor the growth of certain harmful, or bad, microbes, which gradually overtake and suppress the beneficial microbial populations essential for gut health. In this altered environment, the dominant harmful microbes adapt to the stress of ongoing inflammation by producing specific chemicals, known as metabolites that can damage the host’s tissues and further disrupt normal colon function. This is in stark contrast to the activity of microbes in a healthy, stable gut, where the microbial community generates beneficial metabolites that support the host’s well-being and help maintain immune balance. By carefully comparing the composition of the gut microbiome and the types of metabolites present in genetically modified mice with those found in normal lab mice, the researchers were able to identify distinct patterns in how different microbes respond to inflammatory stress and, in some cases, actively worsen it shedding light on the ways microbial shifts and metabolite changes can perpetuate a damaging cycle of inflammation.

In mice engineered with a genetic profile linked to early-onset colitis, researchers observed a clear imbalance in the gut microbiome, marked by an overabundance of harmful, disease-promoting microbes and a significant reduction in beneficial ones a distinct signature of dysbiosis that could be directly tied to an elevated risk of colorectal cancer. Alongside this microbial shift, the team identified several key metabolites that not only correlated with colorectal cancer risk in humans but also appeared consistently in this transgenic mouse model making it a powerful tool for studying disease mechanisms and developing potential interventions. Chen explained that pinpointing which beneficial microbes and their associated metabolites are diminished opens the door for targeted therapeutic strategies. Building on these findings, her team plans to test carefully selected probiotics aimed at restoring the healthy microbial community, and postbiotics beneficial metabolites produced by these microbes to counteract the harmful effects of bad bacteria in an inflamed colon. The ultimate goal, she said, is to evaluate both the live beneficial microbes and the protective compounds they generate as a means to supplement the gut environment and disrupt the progression toward colorectal cancer.

Source: https://fshn.illinois.edu/news/mouse-study-reveals-gut-microbe-balance-may-be-key-factor-early-onset-colorectal-cancer