Intestinal Contributes to Pneumonia by Synthesizing Glutamine in Multiple Myeloma

Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal () enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal is significantly enriched in MM with pneumonia. This enriched intestinal links to the incidence of pneumonia in MM, and intestinal colonization of contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of in MM mice and patients, is synthesized by , and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing -mutated alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut-lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia.