Sustained Minimal Residual Disease Negativity in Multiple Myeloma is Associated with Stool Butyrate and Healthier Plant-Based Diets

Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma (MM). The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We examined the relationship of dietary factors, stool metabolites, and microbial diversity with sustained MRD negativity in patients on lenalidomide maintenance. At 3 months, higher stool butyrate concentration (p=0.037), butyrate producers (p=0.025) and α-diversity (p=0.0035) were associated with sustained MRD-negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (p=0.009) and sustained MRD-negativity (p=0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins p=0.01, flavones p=0.01, and flavanols p=0.02). This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production and sustained MRD-negativity in MM; providing rationale to evaluate a prospective dietary intervention.Statement of SignificanceWe demonstrate an association between diet, the gut microbiome, and sustained MRD-negativity in MM. A healthy diet, with adequate plant and seafood protein, and containing flavonoids, associates with stool diversity, butyrate production and sustained MRD-negativity. These findings suggest dietary modification should be studied to enhance myeloma control.Key PointsIn MM on lenalidomide maintenance, stool butyrate concentration at 3 months was associated with higher rates of MRD negativity at 12 months.Increased seafood and plant proteins, dietary flavonoids, and diversity of dietary flavonoids correlated with stool butyrate concentrations.