Administering Bifidobacterium pseudolongum With Arsenic Trioxide Attenuates Acute Promyelocytic Leukemia in Mice by Restoring Immune Microenvironment and Intestinal Homeostasis

OBJECTIVE: (BP) could mitigate these adverse effects and enhance therapeutic outcomes. METHODS: 16S rRNA gene sequencing data of gut microbiota were obtained from a cohort of 22 APL patients treated with ATO-based regimens (20 of 22 data were obtained and analysis further), accessible under BioProject ID PRJNA935705. To evaluate the within-sample microbial community richness and evenness, alpha and beta diversity indices were calculated. Using a murine APL model, we compared ATO monotherapy with ATO+BP co-treatment. Analyses included fecal metagenomic sequencing, single-cell RNA sequencing (sc-RNA-seq), flow cytometric immune profiling, and assessment of intestinal tight junction proteins (claudin-1, occludin, and ZO-1) via immunofluorescence. RESULTS: ATO treatment significantly reduced gut microbial diversity and depleted beneficial taxa. Sc-RNA-seq data showed that ATO could orchestrate the APL immune microenvironment mainly through functional activation of CD8+ T cells and monocytes. BP supplementation restored microbial homeostasis and synergistically enhanced ATO's antileukemic effect, reducing the leukemic burden in peripheral blood by 72% and in bone marrow by 64% compared to ATO alone. Mechanistically, BP preserved intestinal barrier integrity by upregulating tight junction protein expression and modulated anti-tumor immunity, notably increasing bone marrow CD8+ T cells by 2.21-fold. CONCLUSIONS: BP is an effective adjunct to ATO therapy, counteracting gut dysbiosis, intestinal damage, and the immune microenvironment while synergistically improving antileukemic efficacy. Targeting the gut-leukemia axis with BP represents a promising strategy for improving the precision and safety of APL treatment.