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

ATO treatment significantly reduced gut microbial diversity and depleted beneficial taxa in APL patients.

• 16S rRNA gene sequencing data were obtained from a cohort of 22 APL patients treated with ATO-based regimens, with 20 of 22 samples analyzed.
• Data were accessible under BioProject ID PRJNA935705.
• Alpha and beta diversity indices were calculated to evaluate within-sample microbial community richness and evenness.
• ATO treatment was associated with significant reductions in gut microbial diversity and depletion of beneficial taxa.

Single-cell RNA sequencing revealed that ATO orchestrates the APL immune microenvironment mainly through functional activation of CD8+ T cells and monocytes.

• Sc-RNA-seq was performed on a murine APL model comparing ATO monotherapy with ATO+BP co-treatment.
• ATO was found to modulate the APL immune microenvironment primarily via CD8+ T cell and monocyte functional activation.
• Flow cytometric immune profiling was also used to characterize immune cell populations.

BP supplementation combined with ATO reduced leukemic burden in peripheral blood by 72% and in bone marrow by 64% compared to ATO monotherapy alone.

• These reductions were observed in a murine APL model comparing ATO monotherapy to ATO+BP co-treatment.
• Peripheral blood leukemic burden was reduced by 72% with ATO+BP versus ATO alone.
• Bone marrow leukemic burden was reduced by 64% with ATO+BP versus ATO alone.
• Fecal metagenomic sequencing was used to assess microbial changes in the murine model.

BP supplementation increased bone marrow CD8+ T cells by 2.21-fold compared to ATO monotherapy.

• Flow cytometric immune profiling was used to quantify CD8+ T cell populations in bone marrow.
• The 2.21-fold increase in bone marrow CD8+ T cells was observed in ATO+BP co-treated mice relative to ATO alone.
• This finding indicates that BP modulated anti-tumor immunity in addition to restoring microbial homeostasis.

BP preserved intestinal barrier integrity by upregulating tight junction protein expression in ATO-treated mice.

• Intestinal tight junction proteins assessed included claudin-1, occludin, and ZO-1.
• Expression was evaluated via immunofluorescence in the murine APL model.
• BP supplementation was associated with restoration of tight junction protein expression that was disrupted by ATO treatment.
• These findings indicate BP counteracted ATO-induced intestinal damage.

BP supplementation restored microbial homeostasis that had been disrupted by ATO treatment.

• Fecal metagenomic sequencing was used to characterize gut microbiota changes in mice.
• BP was found to synergistically enhance ATO's antileukemic effect alongside restoring microbial homeostasis.
• The restoration of microbial homeostasis was concurrent with improvements in intestinal barrier integrity and immune microenvironment.