Secretory IgA dysfunction underlies poor prognosis in <i>Fusobacterium</i> -infected colorectal cancer
<i>Fusobacterium nucleatum</i> (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome-both models having been orally gavaged with Fn-jointly validated the causal role of Fn in impairing sIgA induction. We identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised mucosal immunity and increased bacterial infiltration. This IGAM signature effectively stratified Fn-positive patients, suggesting potential for targeted therapeutic approaches. Our findings reveal that Fn disrupts sIgA production, increasing tumor microbial burden and worsening prognosis through chronic inflammation in Fn-positive CRC.
Authors
- Han Sang Kim (ORCID: https://orcid.org/0000-0002-6504-9927)
- Irina Matei (ORCID: https://orcid.org/0000-0002-5712-8430)
- Joong Bae Ahn (ORCID: https://orcid.org/0000-0001-6787-1503)
- Seungbyn Baek (ORCID: https://orcid.org/0000-0002-4039-277X)
- Junha Cha (ORCID: https://orcid.org/0000-0002-3106-5865)
- Insuk Lee (ORCID: https://orcid.org/0000-0003-3146-6180)
- Donghwan Park (ORCID: https://orcid.org/0000-0002-1396-8243)
- Minsun Jung (ORCID: https://orcid.org/0000-0002-8701-4282)
- Susan Bullman (ORCID: https://orcid.org/0000-0002-7713-0810)
- Yoon Dae Han (ORCID: https://orcid.org/0000-0002-2136-3578)
- Kyunga Kim (ORCID: https://orcid.org/0000-0002-0865-2236)
- Ki Taek Nam (ORCID: https://orcid.org/0000-0001-5292-1280)
- Hye-Yeong Jo (ORCID: https://orcid.org/0000-0002-2343-7729)
- Melody Y. Zeng (ORCID: https://orcid.org/0000-0002-0031-4267)
- Sang Cheol Kim (ORCID: https://orcid.org/0000-0003-4389-9178)
- Ilseok Choi
- Jun Hyung
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Incheon National University (KR)
- Yonsei University (KR)
- Cornell University (US)
- Biomass Technology Group (Netherlands) (NL)
- Korea National Institute of Health (KR)
- Children's Cancer and Blood Foundation (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- Gut Microbes
- Published
- 2025-07-16
- DOI
- https://doi.org/10.1080/19490976.2025.2528428
- Citations
- 5
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Korea Health Industry Development Institute
- National Research Foundation of Korea