Microbiome-targeted interventions during gastrointestinal mucositis

Gastrointestinal mucositis (GI-M) remains a significant complication of cancer treatment that severely affects patient’s quality of life and treatment compliance. Patients frequently experience symptoms such as nausea, vomiting, abdominal pain and diarrhea. Ultimately, these symptoms lead to decreased chemotherapeutic dosage or even to a discontinuation of the treatment. Although a plethora of studies have implicated the gut microbiome in the pathobiology of GI-M, there has been relatively scarce research into the development of microbial interventions. As such, the PhD research described in this thesis aimed at describing key mechanisms involved in host-microbe interactions through in-depth longitudinal analyses in preclinical and clinical samples and at investigating the efficacy of several microbial interventions. The results show that, while vitamin C holds promise to reduce GI-M symptomology, Blautia luti and fecal microbiota transplantation (FMT) may support the gut microbiome with greater efficacy. Furthermore, B. luti was also identified as risk predictor in cancer patients undergoing chemotherapy, suggesting that the baseline microbiota is a predictor for toxicity outcomes. Additionally, work from this thesis also shows the challenges in assessing absorption of anti-infectives (e.g., ciprofloxacin and fluconazole) during GI-M, thus demonstrating the need for future studies on the exposure of different anti-infectives routinely used during chemotherapy regimens. Altogether, the results support microbial modulation in supportive care cancer as a promising approach to reduce GI-M in cancer patients. Furthermore, it also contributes to the development of new guideline for the prophylactic treatment with anti-infectives, thus optimizing supportive care in cancer patients.