<i>Lactococcus lactis HkyuLL 10</i> suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38599786.
- Also identified by DOI 10.1136/gutjnl-2023-330835 and PMC identifier 11347254.
- Licence recorded as CC BY-NC.
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Abstract
Probiotic <i>Lactococcus lactis</i> is known to confer health benefits to humans. Here, we aimed to investigate the role of <i>L. lactis</i> in colorectal cancer (CRC). <i>L. lactis</i> abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). <i>L. lactis</i> was isolated from healthy human stools with verification by whole genome sequencing. The effect of <i>L. lactis</i> on CRC tumourigenesis was assessed in transgenic <i>Apc</i> <sup>Min/+</sup> 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 <i>L. lactis</i> conditioned medium (<i>HkyuLL 10</i>-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice. Faecal <i>L. lactis</i> was depleted in patients with CRC. A new <i>L. lactis</i> strain was isolated from human stools and nomenclated as <i>HkyuLL 10. HkyuLL 10</i> supplementation suppressed CRC tumourigenesis in <i>Apc</i> <sup>Min/+</sup> mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including <i>Lactobacillus johnsonii</i> in <i>HkyuLL 10</i>-treated mice. <i>HkyuLL 10</i>-CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to <i>HkyuLL 10</i>-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. <i>HkyuLL 10</i> suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. <i>HkyuLL 10</i> administration may serve as a prophylactic measure against CRC.
Medical subject headings
- Colorectal Neoplasms
- Gastrointestinal Microbiome
- Probiotics
- Lactococcus lactis
- Feces
- alpha-Mannosidase
- Carcinogenesis