Acinetobacter radioresistens, a bacterial species residing in the colonic crypts (small pockets in the lining of the colon), secretes indole acetic acid (IAA), a metabolite, that breaks down food, drugs or chemicals, and its own tissue, that inhibits cell proliferation [rapid increase in the number of cells], promotes intestinal stem cell (ISC) homeostasis and suppresses tumour initiation and colorectal cancer.
Researchers investigated the influence of crypt microbiota on ISC function using bacterial outer membrane vesicles (OMVs). Acinetobacter radioresistens-derived OMVs repressed cellular proliferation in organoids, unlike OMVs from Acinetobacter modestus and Delftia tsuruhatensis. A mutant strain of A. radioresistens, lacking the ability to produce IAA, did not inhibit cell proliferation, confirming IAA's role. A. radioresistens was found to be highly enriched in the colonic crypts of wild bats compared to laboratory mice and healthy tissues from human colorectal cancer (CRC) patients. A. radioresistens-derived OMVs inhibited cell proliferation in human colonoids in an IAA-dependent manner. A. radioresistens-derived IAA acts directly on ISCs, reducing the expression of Wnt-β-catenin signalling targets.
A. radioresistens protects against tumour initiation in APC mice in an IAA-dependent manner. Specific depletion of A. radioresistens using a lytic bacteriophage (Ar-φ) increased the expression of β-catenin and heightened colonic proliferation. Ar-φ treatment promoted tumorigenesis (the process by which normal cells become cancer cells) in an inflammation-induced CRC model.
The protective effect of A. radioresistens involves the aryl hydrocarbon receptor (AhR) - a protein that regulates gene expression in response to environmental compounds. These findings suggest that A. radioresistens protects its host from intestinal tumour initiation by inhibiting Wnt-β-catenin signalling and the level of EphB2 [a receptor tyrosine kinase] in crypts.
* Zhang, S., Peng, L., Goswami, S. et al. Intestinal crypt microbiota modulates intestinal stem cell turnover and tumorigenesis via indole acetic acid. Nat Microbiol (2025).