{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:01:59Z","timestamp":1786978919451,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Immune checkpoint inhibitors have improved outcomes in esophageal cancer across settings, yet clinical benefit remains heterogeneous, with current host-derived biomarkers incompletely predicting response. This mini review evaluates recent studies that integrate gut or intratumoral microbial features with host immune, molecular, or metabolic assessment in esophageal cancer. We classify the evidence using a four-level hierarchy of host-microbiome integration: ecological association, functional association, mechanistic integration, and clinical predictive integration. Tissue studies reveal compartment-specific relationships between microbial diversity or individual taxa and immune architecture, whereas treatment cohorts identify bacterial and fungal signatures associated with pathological or immunotherapy response. Mechanistic studies offer the strongest biological evidence, most notably the Lactobacillus salivarius-indole-3-lactic acid-AhR\/NF-\u03baB axis, which drives CD8-positive T-cell exhaustion and resistance to anti-PD-1 therapy. However, biological integration is substantially more advanced than clinical response prediction. Small cohorts, heterogeneous regimens, contamination of low-biomass samples, coarse taxonomic (rather than functional) resolution, confounding by histology, multi-omic layers measured in different patients, and lack of external validation currently jeopardize integration of microbiome to guide treatment. Future studies should use longitudinal, multicenter, compartment-matched sampling and test whether microbial genes or metabolites improve patient selection and predict clinical response beyond established clinical and host biomarkers.<\/jats:p>","DOI":"10.3390\/cimb48080831","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:42:17Z","timestamp":1786974137000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host-Microbiome Integration as a Biomarker Framework in Esophageal Cancer: Current Evidence and Translational Challenges"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6737-4880","authenticated-orcid":false,"given":"Shamimeh","family":"Pourbahrighesmat","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA"},{"name":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Tojjari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA"},{"name":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Laliotis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA"},{"name":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-9401","authenticated-orcid":false,"given":"Anwaar","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology & Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA"},{"name":"UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1080\/1744666X.2024.2368194","article-title":"Advancements in immunotherapy for advanced esophageal squamous cell carcinoma: A comprehensive review of current strategies and future directions","volume":"20","author":"Zhang","year":"2024","journal-title":"Expert Rev. 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