McGill University
Ph.D. candidate
Supervisor: Corinne Maurice
Bastien Castagner, McGill University
Start: 2024-05-01

Project

Comparing the effects of fructans on the gut microbiota and their influence on anti-PD-1 therapy
Cancer immunotherapy is a powerful treatment for one of the deadliest diseases worldwide. However, 60-70% of patients do not respond to this treatment. Recent research has revealed that the composition of the gut microbiota is linked to cancer patients’ response to anti-PD-1 immunotherapy. Moreover, data in mouse models suggest that modulating the gut microbiota is an effective strategy to re-sensitize cancer patients to anti-PD-1. A diet rich in nondigestible carbohydrates (glycans) has been positively associated with response to cancer immunotherapy. In particular, the diet-derived glycan inulin (IN) has been shown to promote growth of bacteria associated with positive immunotherapy outcome in mouse cancer models. Preliminary data from our lab shows that the anti-tumor effect of dietary glycans is structure specific: in a mouse melanoma model treated with anti-PD-1, mice orally gavaged with IN were more sensitive to anti-PD-1, while levan, which is structurally similar to IN, had no effect. We hypothesize that bacterial metabolism of IN influences the composition and function of the gut microbiota and drives the positive response to anti-PD-1 immunotherapy. We propose to identify these IN-specific mechanisms through the following aims: (1) Evaluate the effect of specific metabolism of prebiotics in a mouse cancer model of anti-PD-1 therapy; (2) Identify and isolate prebiotic-consuming bacteria from healthy human stools; (3) Administer the identified prebiotic-consumers to a mouse model of PD-1 blockade. With this work, we will address whether enrichment of IN-consuming gut bacteria can improve response and the success rate of a life-saving treatment like PD-1 blockade therapy.

Keywords

Gut microbiota, prebiotics, inulin, cancer immunotherapy, CAZymes, bacterial metabolism, fructans

Publications

1- First unraveling of the hidden and intricate evolutionary history of a bacterial group II intron family
LaRoche-Johnston, Félix, Catherine Prattico, Caroline Monat, Olivier Hinse, Benoit Cousineau
2023 Evolution

2- Diagnostic and Management Strategies of Food Protein-Induced Enterocolitis Syndrome: Current Perspectives
Mulé, Angela, Catherine Prattico, Adnan Al Ali, Pasquale Mulé, Moshe Ben-Shoshan
2023 Pediatric Health, Medicine and Therapeutics

3- A Systematic Review of Food Protein-Induced Enterocolitis Syndrome
Prattico, Catherine, Pasquale Mulé, Moshe Ben-Shoshan
2023 International Archives of Allergy and Immunology

4- Identification of novel fructo-oligosaccharide bacterial consumers by pulse metatranscriptomics in a human stool sample
Prattico, Catherine, Emmanuel Gonzalez, Lharbi Dridi, Shiva Jazestani, Kristin E. Low, D. Wade Abbott, Corinne F. Maurice, Bastien Castagner,
2025 mSphere