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Gut Microbiota Dysbiosis Remodels the Multi-Tissue Transcriptional Landscape of the Host

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Editor's note
Dysbiosis affects host gene expression across multiple organs simultaneously—not just locally in the gut—through tissue-specific pathways tied to immunity, metabolism, and cancer outcomes. This mechanistic mapping from a controlled mouse depletion model represents genuine progress beyond correlational microbiome studies, though human validation remains essential. Gastroenterologists, hepatologists, and oncologists investigating dysbiosis-linked disease should track the identified effector genes and ceRNA networks as potential intervention targets.

Source: europepmc · Huang L, Liu S, Xiao S, Li Y, Luo S, Hou E, Wang Y, Zong X. · Research Square · 2026-05-25

URL: https://europepmc.org/article/PPR/PPR1238149

AI rationale (4/5, tier: preliminary): Mechanistic host-microbiota link via multi-tissue transcriptomics in controlled depletion/restoration model; animal study limits tier despite strong relevance to dysbiosis pathways.

<title>Abstract</title> <p> Background The gut microbiota exerts a profound influence on host physiology, but its systemic impact on gene expression across diverse tissues remains poorly characterized. Results This study investigated the transcriptional effects of gut microbiota depletion and restoration in mice across six tissues (colon, jejunum, liver, heart, lung, and kidney) using whole-transcriptome sequencing. We found that the presence of gut microbiota significantly altered the transcriptome, with the most pronounced effects in the colon. Using a linear mixed-effects model, we identified 7,365 effector genes. Tissue-specific analysis revealed that these genes were associated with distinct functional pathways, such as immunity in the gut and lung, and metabolism in the liver. Further refinement with LASSO regression pinpointed gut microbiota-mediated key effector genes, whose expression levels were significantly associated with patient survival in corresponding human cancers (e.g., LIHC, LUAD, KIRC). Furthermore, we observed a widespread remodeling of competing endogenous RNA (ceRNA) networks by the gut microbiota. Single-cell data analysis highlighted a potential gut-liver axis interaction, primarily mediated by colonic enterocytes and hepatic cholangiocytes, meanwhile gut microbiota repressed the transcription initiation of <italic>Noct</italic> in colonic enterocytes, whose expression level was significantly negatively correlated to gut-liver axis interaction. Conclusions Our findings provide a comprehensive map of the multi-tissue transcriptional landscape shaped by the gut microbiota, which regulate immune response of gut-liver axis according to inhibit the transcription of <italic>Noct</italic> , revealing tissue-specific regulatory mechanisms and identifying key genes with potential clinical relevance in cancer. </p>

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Published 2026-05-28 · Last kit-update 2026-05-28