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Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria
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  • Published: 23 January 2026

Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria

  • Francesco Candeliere1,
  • Laura Sola1,
  • Enrico Busi1,
  • Sara Pedroni1,
  • Stefano Raimondi1,2,
  • Alberto Amaretti1,2,
  • Stefano Greco3,
  • Massimo Dominici3 &
  • …
  • Maddalena Rossi  ORCID: orcid.org/0000-0002-5342-39501,2 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer
  • Computational biology and bioinformatics
  • Immunology
  • Microbiology
  • Oncology

Abstract

c-di-AMP is a bacterial second messenger recognized by host immune sensors such as the STING pathway, linking gut microbiota activity to tumor immunity. This interaction holds significant therapeutic potential particularly for oncologic patients, given the increasingly recognized relationship between gut microbiota and tumor immunity. Recent evidence shows that microbial c-di-AMP can enhance anti-tumor responses and improve the efficacy of PD-1/PD-L1 blockade and radiotherapy. This study identified gut microbial species capable of synthesizing c-di-AMP by mining the Unified Human Gastrointestinal Protein catalogue for diadenylate cyclases (DACs), generating a database of 4,228 DACs across 3,901 species out of 4,744 presents in the Unified Human Gastrointestinal Genome catalogue. Analysis of metagenomic data from 190 healthy subjects and 569 cancer patients (melanoma, NSCLC, renal carcinoma) revealed a significantly higher abundance of DAC-encoding species in healthy microbiota, with no differences between responders and non-responders to immunotherapy. These findings indicate that c-di-AMP-producing bacteria are depleted in cancer-associated microbiota, supporting further studies on their role in modulating anti-tumor immunity.

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Data availability

UHGP fasta file, UHGG Kraken2 database and UHGG reference genomes are available at UHGG repository (https://ftp.ebi.ac.uk/pub/databases/metagenomics/mgnify_genomes/human-gut/v2.0.1/). Accession numbers of metagenomes utilized in this work are reported in Suppl. Table 1.

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Funding

The research activities have been funded by PIANO NAZIONALE DI RIPRESA E RESILIENZA(PNRR) - MISSIONE 4 COMPONENTE 2, “Dalla ricerca all’impresa” INVESTIMENTO 1.3, Creazione di “Partenariati estesi alle università, ai centri di ricerca, alle aziende per il finanziamento di progetti di ricerca di base”, finanziato dall’Unione europea - NextGenerationEU” - Progetto identificato con codice PE00000019, Titolo “HEAL ITALIA” - Spoke 5 - CUP E93C22001860006 Avviso MUR DD. 341 del 15.03.2022.

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Authors and Affiliations

  1. Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy

    Francesco Candeliere, Laura Sola, Enrico Busi, Sara Pedroni, Stefano Raimondi, Alberto Amaretti & Maddalena Rossi

  2. Biogest-Siteia, University of Modena and Reggio Emilia, Modena, Italy

    Stefano Raimondi, Alberto Amaretti & Maddalena Rossi

  3. Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy

    Stefano Greco & Massimo Dominici

Authors
  1. Francesco Candeliere
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  2. Laura Sola
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  3. Enrico Busi
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Contributions

Conceptualization: Rossi M, Amaretti A, Raimondi SInvestigation: Candeliere F, Sola LFormal analysis: Candeliere F, Busi ESoftware: Candeliere FVisualization: Candeliere F, Amaretti A, Pedroni SWriting - original draft: Candeliere F, Rossi M, Pedroni S, Sola L, Amaretti A, Raimondi S, Greco S, Dominici MSupervision: Rossi MAll authors contributed to the article and approved the submitted version.

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Correspondence to Maddalena Rossi.

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Candeliere, F., Sola, L., Busi, E. et al. Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35425-5

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  • Received: 13 November 2025

  • Accepted: 06 January 2026

  • Published: 23 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-35425-5

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Keywords

  • c-di-AMP
  • Diadenylate cyclase
  • Human gut microbiota
  • Immunotherapy
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