Table 1.
Treatment toxicity management | ||
---|---|---|
Indication | Rationale | Approach |
Gastrointestinal mucositis | GI toxicity is associated with microbial disruption characterized by a loss of overall species diversity and shift towards a gram-negative enterotype. Although causal relationship remains unclear, interventions targeting the microbiota have proven efficacious in various preclinical models, with varying translational success. |
Personalized donor or synthetic FMT to prophylactically enhance outcomes; requires characterization of optimal microbial phenotypes associated with treatment outcome in unique oncological settings. Therapeutic FMT (autologous or donor) to 1) manage acute diarrhea, 2) promote recovery of microbiota and thus mitigate toxicity in subsequent cycles, and 3) restore/maintain microbial diversity to prevent secondary complications. |
Immunotherapy-induced colitis | A growing evidence base shows stark differences in the microbial composition of patients who develop colitis compared to those that do not. Inconsistencies lie in the microbial phenotype linked with optimal outcomes. | Prophylactic FMT to prevent colitis by modulating microbiota to a composition associated with optimal toxicity profiles. Therapeutic FMT to treat chronic immunotherapy-induced colitis. |
Cognitive impairment | A growing body of data now implicates the gut-brain axis in neurocognitive function, with anecdotal evidence suggesting the microbiome is critical in chemotherapy-induced neuroinflammation. GI complications often occur in comparable patient cohorts as neurocognitive impairment, indicating common underlying mechanisms. Probiotics and dietary interventions aimed at modulating the microbiota have been shown to be effective in mitigating cognitive impairment in other indications. |
Assuming a ‘healthy’ microbiome at baseline, autologous FMT to maintain individual's indigenous microbes and prevent neuroinflammation via modulation of the gut-brain axis. In cases where baseline microbiome composition is compromised, donor FMT may be used prophylactically or therapeutically. |
Secondary complication prevention Infection | Pathogen dominance, bacterial translocation and blood stream infection are more prevalent when the microbiota is compromised. Antibiotics and GI toxicity are both risk factor for blood stream infections in oncology cohorts with the microbiome composition able to predict subsequent infections. A diverse microbiome enhances natural defenses against bacterial translocation and pathogen expansion. |
Autologous or donor FMT to maintain microbial diversity throughout treatment to prevent infectious complications via enhancing defenses (intestinal barrier function, mucus production, antimicrobial peptides, bile acid metabolism) and promoting colonization resistance. |
Graft versus host disease | Species diversity following conditioning chemotherapy predicts GvDH in allo-SCT recipients. | Prophylactic FMT to maintain or restore microbial diversity thus preventing mucosal injury and bacterial translocation; both of which are critical in initiation of GvHD. Therapeutic FMT for the treatment of refractory GvHD. |
Pediatric oncology | ||
Late effects (e.g. metabolic disease) | Chronic deficits are observed in the microbiota of survivors of childhood cancer. Many of the late effect experienced by survivors have been linked with the microbiome (e.g. metabolic syndrome). |
Autologous FMT to restore individual's baseline microbiota composition and prevent late effects associated with chronic microbial disruption. |