Cyclophosphamide alters gut microbiota metabolism and structure in lymphoma-bearing mice: implications for dietary modulation
摘要
Diffuse large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin lymphoma, with a high relapse rate after R-CHOP treatment. Cyclophosphamide (CTX), a key component of R-CHOP, induces gastrointestinal side effects and alters the gut microbiome. This study examined the effect of CTX on gut microbiota metabolism and the role of dietary substrates.
MethodsAn in vitro gut fermentation model was used to analyze the fecal microbiota from tumor-bearing mice treated with CTX. We examined microbial metabolites, gas production, short-chain fatty acids (SCFAs), and microbial community structure in response to inulin, tyrosine, and tryptophan.
ResultsCTX treatment disrupted gut microbiota metabolism, reducing SCFA production (particularly acetate and butyrate) and increasing isovaleric acid from tyrosine metabolism. Inulin utilization was reduced, and gas production (especially hydrogen and CO₂) decreased. Tryptophan fermentation increased hydrogen and hydrogen sulfide. CTX also altered microbiota composition, increasing Proteus, Klebsiella, and Enterococcus, which were associated with higher gas production and lower SCFAs. Inulin enhanced beneficial bacteria (Ligilactobacillus) and reduced pathogenic ones (Klebsiella). Correlation analysis showed that inulin fermentation produced more SCFAs with less gas, while tyrosine and tryptophan fermentations promoted gas but limited SCFA formation.
ConclusionCTX disrupts gut microbiota metabolism, decreasing SCFA production and altering gas production, which may contribute to gastrointestinal side effects. Dietary interventions like inulin may mitigate these effects by restoring microbial balance.