Lactococcus lactis HkyuLL 10 suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase.
Gut
; 73(9): 1478-1488, 2024 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-38599786
ABSTRACT
OBJECTIVE:
Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC).DESIGN:
L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic Apc Min/+ 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 L. lactis conditioned medium (HkyuLL 10-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice.RESULTS:
Faecal L. lactis was depleted in patients with CRC. A new L. lactis strain was isolated from human stools and nomenclated as HkyuLL 10. HkyuLL 10 supplementation suppressed CRC tumourigenesis in Apc Min/+ mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including Lactobacillus johnsonii in HkyuLL 10-treated mice. HkyuLL 10-CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to HkyuLL 10-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:
HkyuLL 10 suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. HkyuLL 10 administration may serve as a prophylactic measure against CRC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Lactococcus lactis
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Probióticos
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Alfa-Manosidase
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Fezes
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Carcinogênese
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Microbioma Gastrointestinal
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Gut
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China