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JK5G postbiotics modulate gut microbiota and metabolome to alleviate cancer-related pain: a randomized controlled
Mengting Chen1, Junhui Zhang2,3, Hong Yang2,3
1Department of Clinical Nutrition, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, China.
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.
Insights
JK5G postbiotics improved cancer pain and quality of life by modulating the gut microbiome and immune response. This study suggests JK5G as a potential adjunct therapy for cancer pain management.
Area of Science:
- Microbiome research
- Immunology
- Oncology
- Metabolomics
Background:
- Cancer-related pain is a significant challenge with current treatments having limitations.
- Opioid-based therapies for cancer pain often result in inadequate relief and adverse effects.
- Modulating the gut-microbiome-immune axis presents a novel therapeutic avenue.
Purpose of the Study:
- To investigate the efficacy of JK5G postbiotics in alleviating cancer-related pain.
- To assess the impact of JK5G on gut microbiota composition, host metabolism, and immune markers.
- To evaluate JK5G's effect on quality of life in cancer patients.
Main Methods:
- A randomized, double-blind, placebo-controlled trial with 149 participants.
- Intervention group received patient-controlled subcutaneous analgesia (PCSA) plus JK5G postbiotics; control group received PCSA plus placebo.
- Primary outcomes: gut microbiota (16S rRNA sequencing) and quality of life (QoL). Secondary outcomes: metabolomics, adverse effects, cytokines, and lymphocyte subsets.
Main Results:
- JK5G significantly improved pain scores, QoL, cognitive, and social functioning.
- Microbiome analysis showed increased beneficial bacteria (e.g., Akkermansia muciniphila, Bifidobacterium) and decreased pathogenic bacteria.
- Metabolomic and immune profiling revealed significant alterations, including increased kynurenic acid, butyric acid, and CD3+CD4+ T cells, with reduced TNF-α.
Conclusions:
- JK5G postbiotics show potential in ameliorating cancer-related pain.
- The mechanism involves reshaping the gut microbiota, modulating host metabolism, and enhancing immune responses.
- JK5G may serve as an effective adjunct therapy for cancer pain, warranting further investigation.
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