Human Fecal Transplantation Modifies the Gut Microbiota but Not Metabolites in Colon Cancer Patient-Derived Xenografts.

Prolonged FMT significantly altered gut microbiota structure in NSG mice bearing CRC patient-derived xenografts.

• FMT increased α-diversity of the gut microbiota
• FMT modified β-diversity of the gut microbiota
• FMT induced distinct changes in bacterial genera
• Gut microbiota was profiled by 16S rRNA sequencing
• Four CRC patient-derived xenograft (CRC PDX) models were used in NSG mice

FMT alone did not affect tumor growth in any of the four CRC PDX models.

• Four distinct CRC PDX models derived from CRC patients were evaluated
• Tumor growth was measured across all models receiving FMT without chemotherapy
• No significant difference in tumor progression was observed between FMT-treated and untreated animals

FOLFOX chemotherapy inhibited tumor progression in all four CRC PDX models.

• FOLFOX consists of folinic acid, fluorouracil, and oxaliplatin
• Tumor inhibition by FOLFOX was observed across all four PDX models tested
• The study used CRC PDX models in NSG mice to evaluate FOLFOX efficacy

FMT enhanced FOLFOX therapeutic efficacy in two of the four CRC PDX models.

• Enhancement of FOLFOX responsiveness was observed in two out of four PDX models
• The remaining two PDX models did not show enhanced FOLFOX efficacy with FMT
• Results support a microbiota-mediated modulation of chemotherapy outcomes
• The differential response across models suggests model-specific or donor-specific microbiota interactions with chemotherapy

Despite substantial microbiota shifts induced by FMT, fecal short-chain fatty acids (SCFAs) and amino acids (AAs) were minimally or not affected.

• SCFAs and AAs were analyzed by mass spectrometry
• FMT exerted 'minimal or no effect on fecal SCFAs and AAs'
• This dissociation between microbiota composition changes and metabolite profiles was observed despite significant α- and β-diversity changes
• The finding indicates that microbiota structural remodeling does not necessarily translate into measurable changes in these selected metabolites

The study used NSG mice bearing CRC patient-derived xenografts as the experimental model for evaluating FMT effects on microbiota, metabolites, tumor growth, and chemotherapy response.

• Four CRC PDX models derived from CRC patients were employed
• NSG (NOD scid gamma) mice were used as hosts
• Gut microbiota profiling was performed by 16S rRNA sequencing
• Metabolite analysis included SCFAs and AAs measured by mass spectrometry
• The study evaluated both FMT alone and FMT combined with FOLFOX chemotherapy