Plant-based whole-food diets are feasible during auto-HCT and are associated with dose-dependent microbiome modulation

Plant-based whole foods may represent a tractable approach to mitigating microbiome disruption and improving outcomes in patients undergoing auto-HCT for multiple myeloma, a population in whom intestinal dysbiosis has been linked with inferior survival. We conducted a single-arm clinical trial at our center, in which participants undergoing auto-HCT (n = 22) received fresh, pre-prepared, plant-based meals for 5 weeks spanning conditioning, neutropenia, and early recovery, with the goal of supporting the consumption of nutrient-dense, high-fiber foods. The primary endpoints were feasibility and tolerability, defined by successful enrollment, and patient-reported intake of study meals. Dietary intake was quantified using prospective food diaries and 24‑hour dietary recall surveys. Secondary endpoints included changes in gut microbiome composition and function assessed by shotgun metagenomic sequencing and stool short-chain fatty acid (SCFA) measurements. The intervention was feasible and generally well tolerated, with all participants consuming delivered meals to some degree, with adherence sufficient to support planned dietary and correlative analyses. Greater intake of study meals was associated with more pronounced shifts in gut microbial communities, including enrichment of SCFA-producing taxa and compositional changes consistent with a fiber-responsive microbiome. Stool SCFA concentrations increased from baseline to the end of the intervention, suggesting a functional impact of the dietary strategy on microbial metabolite production during the peri-transplant period. These findings demonstrate that a plant-based meal delivery intervention is implementable during auto-HCT and suggest dose-dependent modulation of the gut microbiome and its metabolic output. The trial is registered at ClinicalTrials.gov (NCT06559709).