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Streptococcus thermophilus Inhibits Colorectal Tumorigenesis Through Secreting β-Galactosidase.
- Source :
-
Gastroenterology [Gastroenterology] 2021 Mar; Vol. 160 (4), pp. 1179-1193.e14. Date of Electronic Publication: 2020 Sep 11. - Publication Year :
- 2021
-
Abstract
- Background & Aims: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention.<br />Methods: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by β-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing.<br />Results: Oral gavage of S thermophilus significantly reduced tumor formation in both Apc <superscript>min/+</superscript> and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. β-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and β-galactosidase activity assay. β-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional β-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via β-galactosidase. β-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathway kinases, which partially mediated the anticancer effects of S thermophilus.<br />Conclusion: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of β-galactosidase.<br /> (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adenomatous Polyposis Coli Protein genetics
Animals
Azoxymethane administration & dosage
Azoxymethane toxicity
Bacterial Proteins genetics
Cell Line, Tumor
Cell Transformation, Neoplastic chemically induced
Colon microbiology
Colorectal Neoplasms chemically induced
Colorectal Neoplasms genetics
Colorectal Neoplasms microbiology
Humans
Intestinal Mucosa microbiology
Male
Mice
Mice, Transgenic
Neoplasms, Experimental chemically induced
Neoplasms, Experimental genetics
Neoplasms, Experimental microbiology
Neoplasms, Experimental prevention & control
Probiotics metabolism
Streptococcus thermophilus genetics
beta-Galactosidase genetics
Bacterial Proteins metabolism
Colorectal Neoplasms prevention & control
Probiotics administration & dosage
Streptococcus thermophilus enzymology
beta-Galactosidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 160
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 32920015
- Full Text :
- https://doi.org/10.1053/j.gastro.2020.09.003