MM risk: Influences of diet and the microbiome

Multiple myeloma (MM) is the second most commonly diagnosed hematologic malignancy and is characterized by the neoplastic proliferation of plasma cells.¹ While continued research and the development of new treatments for MM have improved survival rates of patients, it is becoming increasingly important to address dietary and lifestyle factors in order to maximize positive clinical outcomes. In particular, diet and microbiome composition play key roles in the absorption and utilization of energy gained from nutritional intake, whilst influencing immunologic stimuli and the regulation of cytokine secretion in intestinal epithelial cells.

Existing and emerging data clearly demonstrate the impact of changes in the gut microbiome on the development of certain malignancies through increased inflammation and other host-microbiome interactions.¹

Recently, Shah et al.¹ published a review of current evidence on diet and the microbiome as potential modifiers of MM risk and the mechanisms by which these factors may influence disease development and progression. We summarize the key findings here.

Impact of dietary components on MM risk

Diet remains one of the major modifiable risk factors for cancer. Several dietary components have been shown to significantly influence the risk of developing MM, as summarized in Figure 1. The effects of certain vitamins and minerals on MM risk are outlined in Figure 2.

GI, glycemic index; IGF-1, insulin growth factor-1; IL-6, interleukin-6; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma.
*Adapted from Shah, et al.¹

 

IGF-1, insulin growth factor-1; IL-6, interleukin-6; ISS, International Staging System; MM, multiple myeloma; NF-kB, nuclear factor-kappa B.
*Adapted from Shah, et al.¹

Alcohol and smoking

• There are currently contradictory results regarding alcohol consumption and the risk of MM when compared with overall cancer risk; some studies have even indicated an inverse association.
• This may reflect the immune system impairment in heavy drinkers, but the enhancement of cellular and immune responses in light drinkers.
• Low alcohol consumption has also shown improved insulin sensitivity, leading to a decrease in the risk of diabetes and obesity; both of which are related to plasma cell disorders.
• In addition, red wine contains the antioxidant resveratrol, which has been shown to induce apoptosis, modulate gut microbiota, and suppress T-helper 17 lymphocytes, which are involved in MM pathogenesis.
• There is currently no clear link between smoking and the risk of MM.

Microbiome

• Intestinal dysbiosis is common in patients with MM.
• Alpha diversity has been shown to be significantly decreased in patients with MM compared with healthy individuals, along with higher levels of Bacteroides, Faecalibacterium, and Roseburia genera.
• Some studies have highlighted an association between intestinal microbiota composition and deeper treatment responses.
  • Higher levels of butyrate producers have been associated with sustained measurable residual disease.
• Several ongoing studies are investigating nutritional strategies to positively modulate the gut microbiota, including:
  • NUTRIVENTION (NCT04920084), which is investigating nutrition-based intervention for patients with elevated body mass index and monoclonal gammopathy of undetermined significance or smoldering MM.
  • NCT05640843, which is evaluating a whole food plant-based diet compared with omega‑3 fatty acids and curcumin supplements and placebo.
  • PROFAST (NCT05565638), which is investigating prolonged nightly fasting in patients with monoclonal gammopathy of undetermined significance and smoldering MM and elevated body mass index.

Conclusion

The risk of MM has been shown to be lower in individuals who eat a plant-based diet when compared with meat eaters. The consumption of fruit, cruciferous vegetables, fish, and whole grains have all been shown to reduce the risk of MM. Patients diagnosed with MM consistently present with a vitamin D deficiency, which negatively impacts myeloma activity, bone turnover, and survival outcomes. Dysregulation of the microbiome is regularly observed in patients with MM, and several studies are currently investigating the effects of diet and supplementation, with a particular emphasis on increasing butyrate-producing bacteria.