JK5G postbiotics modulate gut microbiota and metabolome to alleviate cancer-related pain: a randomized controlled trial with multi-omics integration

Introduction Cancer-related pain remains a critical clinical challenge, with existing opioid-based therapies often yielding inadequate relief and significant side effects. This study investigates the therapeutic potential of JK5G postbiotics—a formulation of inactivated Lactobacillus strains and metabolites—in modulating the gut-microbiome-immune axis to alleviate pain in cancer patients. Methods This study employs a randomized, double-blind, placebo-controlled trial design involving 149 participants divided into two groups: a control group receiving patient-controlled subcutaneous analgesia (PCSA) plus placebo, and an experimental group receiving PCSA plus JK5G postbiotics. The primary outcomes were changes in gut microbiota composition assessed by 16S rRNA gene sequencing, and quality of life (QoL). The secondary outcomes included fecal metabolomics, adverse effects (AEs), blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2500108811). Results JK5G supplementation significantly improved pain scores, QoL, and cognitive and social functioning compared to controls. Microbiome analysis revealed enrichment of beneficial taxa such as Akkermansia muciniphila and Bifidobacterium , alongside suppression of pathogenic Escherichia-Shigella . Machine learning identified five core microbial biomarkers ( Akkermansia muciniphila , Bifidobacterium , Escherichia-Shigella , Blautia , Streptococcus ), with SHAP analysis highlighting Akkermansia muciniphila and Bifidobacterium as top contributors. Metabolomic profiling demonstrated upregulation of 236 metabolites, including kynurenic acid and butyric acid, with tryptophan and butyrate metabolism emerging as key altered pathways. Immune profiling showed elevated CD3 + CD4 + T cells and reduced TNF-α levels, while MIMOSA2 analysis linked microbial taxa to metabolic shifts, such as correlations between Ruminococcus torques and butyric acid. Conclusion These findings suggest that JK5G may contribute to the amelioration of cancer-related pain by reshaping gut microbiota, modulating host metabolism, and enhancing immune responses. This study highlights the potential of JK5G postbiotics as an adjunct therapy, supporting the need for further validation in larger cohorts and mechanistic investigations to advance its clinical translation. Clinical Trial Registration https://www.chictr.org.cn/showproj.html?proj=285304 , identifier ChiCTR2500108811.