Chemotherapy Alters Microbiota to Rewire Immunity

It is well-known that chemotherapy frequently damages the intestinal lining, but less so that this damage reaches well beyond the gut impacting the nutrients available to intestinal bacteria, prompting the microbiota to adapt. According to a new study from the University of Lausanne, this adaptation also increases the production of indole-3-propionic acid (IPA), a metabolite derived from tryptophan.

Instead of remaining in the gut, IPA travels throughout the body and acts as a systemic messenger. It migrates to the bone marrow, where it influences immune cell production. Elevated IPA levels reprogram myelopoiesis, lowering the generation of immunosuppressive monocytes that are known to support immune evasion and the spread of cancer. This shift is linked to a less favorable environment for metastasis.

“We were surprised by how a side effect often seen as collateral damage of chemotherapy can trigger such a structured systemic response. By reshaping the gut microbiota, chemotherapy sets off a cascade of events that rewires immunity and makes the body less permissive to metastasis,” says Ludivine Bersier, first author of the study published in Nature Communications.

This immune reconfiguration enhances T-cell activity and modifies immune interactions within metastatic niches, particularly in the liver. In preclinical models, these changes create a metastasis-refractory state, where metastases are less able to establish and grow.

The findings from animal models are supported by patient data. In collaboration with Thibaud Koessler from Geneva University Hospitals, the team observed that patients with colorectal cancer who had higher circulating levels of IPA after chemotherapy also showed lower monocyte counts. This pattern corresponds with improved survival outcomes, suggesting clinical relevance of the IPA-mediated pathway.

“This work shows that the effects of chemotherapy extend far beyond the tumor itself. By uncovering a functional axis linking the gut, the bone marrow and metastatic sites, we highlight systemic mechanisms that could be harnessed to durably limit metastatic progression,” explains corresponding author Tatiana Petrova.

The study proposes that chemotherapy can create a lasting biological “memory” through microbiota-derived metabolites that suppress metastatic growth. Together, the findings reveal a gut–bone marrow–liver axis through which chemotherapy exerts durable systemic effects, offering new directions for microbiota-based therapeutic strategies.