Table 2_Microbiota-derived metabolic priming of CAR-T cell fitness: a translational framework for next-generation cell therapy.docx

Emerging evidence identifies the gut microbiota as an extratumoral determinant of CAR-T efficacy, persistence, and toxicity. However, taxonomic signatures associated with clinical outcomes show limited reproducibility and are influenced by antibiotics, geography, diet, and methodological heterogeneity.

Building on prior reviews addressing microbiome–CAR-T associations and CAR-T-cell immunometabolism separately, here we synthesize clinical, translational, and preclinical evidence into an integrated, metabolome-centered framework spanning the full CAR-T treatment and manufacturing trajectory. Broad-spectrum antibiotic exposure disrupts microbial metabolic output, depleting short-chain fatty acids, indole derivatives, and other bioactive metabolites, and has been associated with inferior clinical outcomes in several cohorts, although these associations are heterogeneous and may be confounded by baseline disease severity, systemic inflammation, and infection-related factors.