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A High-Fiber Plant-Based Diet Delays Progression to Myeloma in Precursor Disorders

ABSTRACT: Consumption of a western diet and high body mass index (BMI) are risk factors for progression from pre-malignant phenotypes to multiple myeloma, a hematologic cancer. In the NUTRIVENTION trial (NCT04920084), we administered a high-fiber plant-based diet to patients with myeloma precursor states and elevated BMI. The intervention was feasible, improved quality of life and modifiable risk factors: metabolic (BMI, insulin resistance), microbiome (diversity, composition), and immune (inflammation, monocyte subsets). Disease-progression trajectory improved in two participants and was stable in others. In Vk*MYC+/- mice modeling the myeloma-precursor state, a high-fiber diet delayed disease progression through improved microbiome composition and increased short-chain fatty acid production that reinvigorated anti-tumor immunity and inhibited tumor growth. These effects resulted from fiber consumption and were independent from calorie restriction-induced weight loss.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311602 | GEO | 2026/02/12

REPOSITORIES: GEO

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Project description:We investigate the hypothesis that consistent changes in the human gut microbiome are associated with Crohn's disease, a form of inflammatory bowel disease, and that altered microbiota contributes to pathogenesis. Analysis of this problem is greatly complicated by the fact that multiple factors influence the composition of the gut microbiota, including diet, host genotype, and disease state. For example, data from us and others document a drastic impact of diet on the composition of the gut microbiome. No amount of sequencing will yield a useful picture of the role of the microbiota in disease if samples are confounded with uncontrolled variables. We aim to characterize the composition of the gut microbiome while controlling for diet, host genotype, and disease state. Diet is controlled by analyzing children treated for Crohn's disease by placing them on a standardized elemental diet, and by testing effects of different diets on the gut microbiome composition in adult volunteers. Genotype is analyzed by large scale SNP genotyping, which is already underway and separately funded--team member Hakon Hakonarson is currently genotyping 50 children a week at ~half a million loci each and investigating connections with inflammatory bowel disease. Clinical status is ascertained in the very large IBD practice in the UPenn/CHOP hospital system. Effects of diet, host genotype, and disease state on the gut microbiome are summarized in a multivariate model, allowing connections between microbiome and disease to be assessed free of confounding factors. This project is divided into four sub-studies. In the Fecal Storage Methods (FSM) study, methods of stool storage and DNA extraction are compared to examine their impact on DNA sequence analysis results. The Controlled Feeding Experiment (CaFE) addresses the effects of controlled diets on the gut microbiome. In the Cross-sectional Study of Diet and Stool Microbiome Composition (COMBO), the effects of diet analyzed using surveys and deep sequencing of stool specimens. The fourth study, Pediatric Longitudinal Study of Elemental Diet and Stool Microbiome Composition (PLEASE), examines the effects of an elemental diet treatment on pediatric patients diagnosed with inflammatory bowel disease (IBD), particularly Crohn's disease. <ul> <li>Fecal Storage Methods (FSM): Cross-sectional study</li> <li>Controlled Feeding Experiment (CaFE): Controlled trial</li> <li>Cross-sectional Study of Diet and Stool Microbiome Composition (COMBO): Cross-sectional study</li> <li>Pediatric Longitudinal Study of Elemental Diet and Stool Microbiome Composition (PLEASE): Longitudinal cohort study</li> </ul>

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A High-Fiber Plant-Based Diet Delays Progression to Myeloma in Precursor Disorders

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