PhD Student San Raffaele Scientific Institute Milano, Lombardia, Italy
Introduction: The gut microbiota may impact MM development and progression. We have previously demonstrated that Prevotella heparinolytica, a human commensal, expands Th17 cells that migrate to the bone marrow (BM) were they sustain myeloma plasma cells growth. Conversely, P. melaninogenica delays MM progression by limiting Th17 expansion. Through degradation of dietary fibers, Prevotellae generate immunomodulatory short-chain fatty acids (SCFAs) which reduce Th17 differentiation. Thus, we hypothesized that the administration of a high-fiber diet, by expanding SCFA-producing bacteria, restrains Th17 expansion and prevents MM evolution.
Methods: C57BL/6J mice challenged with Vk*MYC-derived MM cells and transgenic Vk*MYC affected by asymptomatic MM (Early-MM) were orally fed with a high-fiber diet. Gut and BM T cell infiltration and effector functions, along with effects on disease progression and overall mouse survival were taken as indicative of high-fiber diet mediated effects. To assess the impact of dietary fibers on gut microbiota composition 16S ribosomal RNA sequencing was performed on stool samples. SCFAs were quantified by NMR.
Results: The administration of high-fiber diet in mice challenged with MM cells (t-Vk*MYC) delayed disease appearance and prolonged mice survival. Early-MM VK*MYC mice are being enrolled in a trial investigating the capacity of fiber-rich diet to delay progression to symptomatic (Late)-MM. Because high-fiber diet expands SCFA-producing Prevotellae and mice treated with P. melaninogenica produced higher levels of SCFAs than P. heparinolytica, we treated t-Vk*MYC mice with butyrate. Treatment with butyrate reduced MM aggressiveness in MM mice reducing the Th17/T regulatory cell ratio.
Conclusions: Modulation of the gut microbiota by probiotics and postbiotics may substantially modulate the immune response thus intercepting the trajectory of MM evolution.
