During the IHMC 2024 Congress recently held in Rome, Microbiomepost discussed with Lisa Derosa, oncologist at Gustave Roussy Hospital in Paris about the link between gut dysbiosis and cancer, shedding light on its role in immunotherapy resistance and patient survival. The discussion highlighted that cancer itself is associated with a distinct form of dysbiosis, characterized by reduced levels of MAdCAM, a key protein found in intestinal venules. Low MAdCAM levels have been linked to decreased survival rates in patients with lung, kidney, and bladder cancers, suggesting that the gut microbiota plays a critical role in modulating the immune response and overall prognosis.
One of the most striking findings presented at the congress involved the role of Akkermansia muciniphila, a bacterium known for its immunogenic properties. Researchers found that the absence or overabundance of Akkermansia can significantly impact clinical outcomes. An overabundance of Akkermansia is particularly problematic, as it disrupts the microbial balance, allowing pathogenic bacteria such as Enterococci and Clostridia to proliferate. In contrast, a balanced presence of Akkermansia is typically associated with the co-existence of beneficial bacteria like Faecalibacterium prausnitzii.
To further investigate these microbial interactions, the research team developed a bacterial network analysis, identifying seven distinct clusters that are strongly associated with patient survival. The analysis revealed two major groups: one, termed the “Spice Interacting Group 1”, comprises bacteria linked to poor survival outcomes, while the other consists of 45 bacteria associated with longer survival. These bacterial communities interact in a complex manner, much like predators and prey in an ecological network, competing and cooperating in ways that ultimately influence patient outcomes.
To translate these findings into clinical practice, the researchers proposed a novel “microbiota score“. This scoring system evaluates the relative abundance of bacteria associated with either favorable or unfavorable prognoses, providing a quantitative measure to predict patient response to immunotherapy. Patients with a higher proportion of beneficial bacteria are more likely to respond positively to immunotherapy and achieve longer survival, while those with a dominance of harmful bacteria may face poorer outcomes.
The next steps involve validating this scoring system through a prospective study in France, utilizing faster analysis methods like qPCR to streamline the process. The researchers also aim to expand the definition of gut dysbiosis to incorporate multi-omic data, including blood-based biomarkers, which would enable more comprehensive stratification of patients. This approach could pave the way for targeted interventions to modify the gut microbiome, enhancing the effectiveness of cancer treatments and improving personalized care.
