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

JK5G postbiotic supplementation significantly improved pain scores and quality of life compared to placebo in cancer patients receiving PCSA.

• The trial was randomized, double-blind, and placebo-controlled with 149 participants.
• Participants were divided into a control group (PCSA plus placebo) and an experimental group (PCSA plus JK5G postbiotics).
• Primary outcomes included changes in gut microbiota composition assessed by 16S rRNA gene sequencing and quality of life (QoL).
• Cognitive and social functioning were also significantly improved in the JK5G group compared to controls.

JK5G supplementation enriched beneficial gut microbial taxa and suppressed pathogenic bacteria.

• Beneficial taxa enriched included Akkermansia muciniphila and Bifidobacterium.
• Pathogenic Escherichia-Shigella was suppressed in the JK5G group.
• Machine learning identified five core microbial biomarkers: Akkermansia muciniphila, Bifidobacterium, Escherichia-Shigella, Blautia, and Streptococcus.
• SHAP analysis highlighted Akkermansia muciniphila and Bifidobacterium as the top contributors among the identified biomarkers.

Fecal metabolomic profiling revealed upregulation of 236 metabolites following JK5G supplementation, with tryptophan and butyrate metabolism identified as key altered pathways.

• 236 metabolites were upregulated in the JK5G group.
• Key upregulated metabolites included kynurenic acid and butyric acid.
• Tryptophan metabolism and butyrate metabolism emerged as the key altered metabolic pathways.
• MIMOSA2 analysis linked specific microbial taxa to metabolic shifts, including correlations between Ruminococcus torques and butyric acid.

JK5G supplementation modulated immune profiles, elevating CD3+CD4+ T cells and reducing TNF-α levels.

• Immune profiling showed elevated CD3+CD4+ T cells in the JK5G group compared to controls.
• TNF-α levels were reduced in the JK5G group.
• Blood inflammatory cytokines and lymphocyte subsets were included as secondary outcome measures.
• These immune changes suggest modulation of the gut-microbiome-immune axis by JK5G postbiotics.

JK5G postbiotics are a formulation of inactivated Lactobacillus strains and metabolites designed to modulate the gut-microbiome-immune axis.

• JK5G is classified as a postbiotic formulation consisting of inactivated Lactobacillus strains and their metabolites.
• The intervention was administered as an adjunct to patient-controlled subcutaneous analgesia (PCSA).
• The study was registered at www.chictr.org.cn with identifier ChiCTR2500108811.
• The rationale was based on the hypothesis that gut microbiome modulation could alleviate cancer-related pain, for which existing opioid-based therapies often yield inadequate relief and significant side effects.

The authors conclude that JK5G postbiotics show potential as an adjunct therapy for cancer-related pain but require further validation in larger cohorts and mechanistic investigations.

• The study highlights the need for larger cohort studies to validate these findings.
• Mechanistic investigations are recommended to advance clinical translation of JK5G postbiotics.
• The findings suggest JK5G may contribute to amelioration of cancer-related pain through reshaping gut microbiota, modulating host metabolism, and enhancing immune responses.
• The multi-omics integration approach (16S rRNA sequencing, metabolomics, immune profiling, and machine learning with SHAP analysis) was used to characterize the mechanisms.