Intestinal Klebsiella pneumoniae Contributes to Pneumonia by Synthesizing Glutamine in Multiple Myeloma

Abstract

Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal <i>Klebsiella pneumonia</i> (<i>K. pneumonia</i>) 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 <i>K. pneumonia</i> is significantly enriched in MM with pneumonia. This enriched intestinal <i>K. pneumonia</i> links to the incidence of pneumonia in MM, and intestinal colonization of <i>K. pneumonia</i> 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 <i>K. pneumonia</i> in MM mice and patients, is synthesized by <i>K. pneumonia</i>, 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 <i>glnA</i>-mutated <i>K. pneumonia</i> alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal <i>K. pneumonia</i> 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.