AIRRWAS integrates TCR-microbiome data to reveal how the gut microbiome shapes the circulating and mucosal T cell repertoire
Year: 2026
Type: article
Study design: Observational Study
Abstract: The gut microbiome modulates mucosal immunity and contributes to multiple diseases, but the extent to which it shapes circulating and mucosal T cell repertoires remains unclear. Here, we paired CD4 + and CD8 + T cell receptor (TCR) sequencing with fecal 16S rRNA microbiome profiling and developed adaptive immune receptor repertoire-wide association study (AIRRWAS), a framework integrating computational TCR-microbiome interaction analysis with targeted in vitro validation. Across three independent cohorts, AIRRWAS identified reproducible associations between convergent TCR clusters and 21 bacterial genera, including core commensals, probiotics, and taxa with immunomodulatory roles. Predicted clonotypes were enriched in genus-specific interaction networks and preferentially activated by matched bacterial stimuli. These findings reveal conserved microbiome-driven immune signatures across distinct repertoires and demonstrate that the gut microbiome shapes both local and circulating T cell populations, providing a resource for biomarker discovery, immune monitoring, and microbiome-targeted therapies.
Source: Cell Reports
Authors: Romi Vandoren, My Ha, Vincent M.L. Van Deuren, Naomi De Roeck, Ting Pu, Eelco C. Brand, Maria Kuznetsova, Hajar Besbassi, Esther Bartholomeus, Fabio Affaticati, Ilke De Boeck, Thies Gehrmann, Sarah Lebeer, Bas Oldenburg, Femke van Wijk, Peter Delputte, Sara Verbandt, Sabine Tejpar, Kris Laukens, Benson Ogunjimi, Pieter Meysman
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Universitaire Stichting, Chan Zuckerberg Initiative, European Commission, ZonMw, Fonds Wetenschappelijk Onderzoek, Universitair Medisch Centrum Utrecht, Vlaamse Interuniversitaire Raad, Vlaamse regering, National Institutes of Health, Horizon 2020, National Institute of Allergy and Infectious Diseases, HORIZON EUROPE Reforming and enhancing the European Research and Innovation system
Awards: Characterization of the phenotypic plasticity of IL17-producing T cells during colorectal cancer development and their interactions with the microbiome, Microbe-mucin isoform crosstalks mediating mucosal barrier function in the gastrointestinal tract versus vagina., G3366597378, G467291571, Celluloepidemiology: generating and modeling SARS-COV-2 specific T-cell responses on a population level for more accurate interventions in public health, G6223678181, Immunoinformatics to discover novel diagnostics in Lyme arthritis: can T cells unlock the status quo?, T-cell receptor diversity and AT-rich DNA sensing by glial cells as key features in controlling neurological varicella-zoster virus infections., G7505034767, G7950610120, RAPTOR: a novel multi-view integrative framework to identify key features of T cell based immunology.
OpenAlex ID: W7162794446