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Gut Microbiota and Gastrointestinal Toxicity From Proteasome Inhibitors in Myeloma

By: Joshua Swore, PhD
Posted: Tuesday, October 18, 2022

Gut biodiversity has been found to be lower in patients with multiple myeloma experiencing gastrointestinal (GI) adverse events, according to a study presented at the 2022 International Myeloma Society (IMS) Annual Meeting and Exposition (Abstract P-029). “Short chain fatty acids may improve GI toxicity via alleviating bowel inflammation,” according to Junling Zhuang, PhD, of Peking Union Medical College Hospital, China, and colleagues. “The translation of these findings to bedside may improve drug tolerance and response.”

A total of 85 patients were enrolled in the study. Patients were split into four groups and treated with various combinations of lenalidomide, dexamethasone, bortezomib, ixazomib, and cyclophosphamide. All groups contained patients with similar age, sex, paraprotein type, and disease stage; all cases presented similar microbiotic diversity.

The researchers reported a significant difference in microbiotic diversity within the 18 patients who experienced gastrointestinal adverse events. Firmicutes, Ruminococcaceae, and Faecalibacterium prausnitzii populations were significantly reduced in these patients. However, multivariate analysis revealed that Faecalibacterium prausnitzii alone was an independent factor associated with gastrointestinal adverse events.

The authors supported their findings by conducting in vivo studies using a mouse model. They notably reported that mice treated with bortezomib underwent a significant reduction in the biodiversity of gut microbiot,a with a prominent decrease in Faecalibacterium prausnitzii bacteria. The authors also noted that the bortezomib-treated mice were able to recover weight and abundance of Faecalibacterium prausnitzii when also treated with butyrate. This led the authors to a suggest that the results of their study may be used to provide a future treatment for patients with gastrointestinal adverse events.

Disclosure: No authors’ disclosures were provided.

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