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.