GEOTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311912GEOGSEfalseProbiotics Complex Synergizes with FOLFOX to Enhance Antitumor Response and Ameliorate Chemotherapy-induced Intestinal Toxicity via Upregulation of NAD+ MetabolismModulating the gut microbiota can improve chemotherapy efficacy, but strategies that simultaneously reduce toxicity and enhance therapeutic outcomes remain understudied. This study developed a NAD⁺-enhanced composite probiotic formulation (derived from fermented yak milk from the Qinghai-Tibet Plateau) to alleviate FOLFOX-induced intestinal toxicity and enhance efficacy in a colitis-associated colorectal cancer (CAC) mouse model. Metabolomics revealed significant contributions of nicotinic acid and nicotinamide metabolism to the body's response to chemotherapy. Consequently, RNA-seq was employed to validate the criticality of nicotinamide metabolism at the gene expression level: probiotics counteracted FOLFOX-induced NAD⁺ depletion, restored SIRT1/3 activity, and suppressed FoxO3a-mediated chemotherapy resistance. A clinical cohort of 53 gastrointestinal cancer patients confirmed serum NAD⁺ levels correlate with gut microbiota and intestinal toxicity. Collectively, we propose a microbiota-targeting strategy synergizing with FOLFOX, providing a translatable paradigm for precision oncology.2026/06/01GSE311912GSM9334413GSM9334414GSM9334411GSM9334412GSM9334417GSM9334418GSM9334415GSM9334416GSM9334398GSM9334399GSM9334410GSM9334396GSM9334397GSM9334408GSM9334409GSM9334402GSM9334403GSM9334422GSM9334400GSM9334401GSM9334406GSM9334407GSM9334404GSM9334405GSM9334420GSM9334421GSM933441924247311912Mus musculus