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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Gut-liver axis in liver pre-metastatic niche formation: immune networks, microbial, and metabolic and emerging therapeutic opportunities

  • Leyi Zhao1,2
  • Qiutong Lin3
  • Danyuan Zhang2
  • Yani Liu1,4
  • Mingtong Zong1,2
  • Lingze Xi1,2
  • Feiyu Xie5
  • Shuyi Song6
  • Peng Xue1
  • Shijie Zhu1
  • Xuelei Chu7
7 affiliations
  1. 1Department of Oncology, Wangjing Hospital of China Academy of Traditional Chinese Medicine
  2. 2Graduate School, Beijing University of Chinese Medicine
  3. 3Qi - Huang Chinese Medicine School, Beijing University of Chinese Medicine
  4. 4Department of Integrated Traditional Chinese and Western Medicine Oncology, China-Japan Friendship Hospital
  5. 5The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
  6. 6Affiliated Hospital of Qingdao University
  7. 7Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences
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Abstract

The liver is a leading target for distant metastasis across multiple cancer types, and liver metastasis invariably portends poor prognosis. The formation of pre-metastatic niches (PMNs) within the hepatic microenvironment creates a permissive “soil” for disseminated tumor cells. However, how the gut-liver axis integrates microbial and metabolic signals to remodel the hepatic PMN remains incompletely understood. In this review, we delineate the six hallmark features of PMN assembly, with an emphasis on the complex crosstalk among gut microbiota, their bioactive metabolites, and resident liver cells—including hepatocytes and hepatic immune populations. Notably, these elements engage in a dynamic, reciprocally regulated network characterized by bidirectional feedback loops, rather than a linear signaling cascade. We further survey the emerging landscape of diagnostic biomarkers, including exosomal microRNAs and neutrophil extracellular traps, alongside microbiota-targeted therapeutic interventions. This framework provides testable hypotheses for early interception of liver metastasis and highlights precision medicine opportunities targeting the gut-liver-immune axis.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026gutliver,
  title = {{Gut-liver axis in liver pre-metastatic niche formation: immune networks, microbial, and metabolic and emerging therapeutic opportunities}},
  author = {Leyi Zhao and Qiutong Lin and Danyuan Zhang and Yani Liu and Mingtong Zong and Lingze Xi and Feiyu Xie and Shuyi Song and Peng Xue and Shijie Zhu and Xuelei Chu},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1931054},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1931054/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gut-liver axis in liver pre-metastatic niche formation: immune networks, microbial, and metabolic and emerging therapeutic opportunities
AU  - Leyi Zhao
AU  - Qiutong Lin
AU  - Danyuan Zhang
AU  - Yani Liu
AU  - Mingtong Zong
AU  - Lingze Xi
AU  - Feiyu Xie
AU  - Shuyi Song
AU  - Peng Xue
AU  - Shijie Zhu
AU  - Xuelei Chu
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1931054
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1931054/full
AB  - The liver is a leading target for distant metastasis across multiple cancer types, and liver metastasis invariably portends poor prognosis. The formation of pre-metastatic niches (PMNs) within the hepatic microenvironment creates a permissive “soil” for disseminated tumor cells. However, how the gut-liver axis integrates microbial and metabolic signals to remodel the hepatic PMN remains incompletely understood. In this review, we delineate the six hallmark features of PMN assembly, with an emphasis on the complex crosstalk among gut microbiota, their bioactive metabolites, and resident liver cells—including hepatocytes and hepatic immune populations. Notably, these elements engage in a dynamic, reciprocally regulated network characterized by bidirectional feedback loops, rather than a linear signaling cascade. We further survey the emerging landscape of diagnostic biomarkers, including exosomal microRNAs and neutrophil extracellular traps, alongside microbiota-targeted therapeutic interventions. This framework provides testable hypotheses for early interception of liver metastasis and highlights precision medicine opportunities targeting the gut-liver-immune axis.
SN  - 1664-302X
ER  -