suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase.

Objective: Probiotic is known to confer health benefits to humans. Here, we aimed to investigate the role of in colorectal cancer (CRC).

Design: abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). was isolated from healthy human stools with verification by whole genome sequencing. The effect of on CRC tumourigenesis was assessed in transgenic mice and carcinogen-induced CRC mice. Faecal microbiota was profiled by metagenomic sequencing. Candidate proteins were characterised by nano liquid chromatography-mass spectrometry. Biological function of conditioned medium (-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice.

Results: Faecal was depleted in patients with CRC. A new strain was isolated from human stools and nomenclated as supplementation suppressed CRC tumourigenesis in mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including in -treated mice. -CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to -secreted proteins, and we identified that α-mannosidase was the functional protein. The antitumourigenic effect of α-mannosidase was demonstrated in human CRC cells and organoids, and its supplementation significantly reduced tumour growth in xenograft mice.

Conclusion: suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. administration may serve as a prophylactic measure against CRC.