Factors underlying the association between Streptococcus gallolyticus, subspecies gallolyticus infection and colorectal cancer: a mini review.

Gut microbiome (Cambridge, England) Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI:10.1017/gmb.2024.11
David Michael Warner, Arunab Harish Mehta
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Abstract

Streptococcus gallolyticus, subspecies gallolyticus (Sgg) is a gram-positive bacterium associated with infective endocarditis and colorectal cancer (CRC). Sgg has features that allow the bacterium to thrive in the colorectal tumor microenvironment and further progress the development of CRC to facilitate its survival. Sgg contains 3 pili that facilitate colonic cell adhesion and translocation through phase variation. Sgg also contains bile salt hydrolase and a bacteriocin called gallocin with substantially increased activity in bile acids, which facilitates its growth in the bile acid-rich adenomatous colorectal microenvironment. Sgg also uses tumor metabolites as an energy source. Sgg also possesses tannase, which metabolizes gallotannin to be used as a carbon source and reduces the anti-apoptotic effects of tannins, driving CRC progression. Sgg also interferes with a variety of oncogenic cell signaling pathways, including the Wnt/β-catenin pathway through mechanisms that are not fully elucidated. Increased β-catenin signaling also enhances adhesion via increased expression of the extracellular matrix and increases bile acid concentrations in the lumen through downregulation of an apical bile acid transporter. Finally, Sgg induces biotransformation of toxic substrates in CRC cells, which leads to formation of toxic intermediates and DNA adducts, promoting further progression of CRC.

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溶胆链球菌、溶胆链球菌亚种感染与结直肠癌相关因素综述
溶胆链球菌亚种(Sgg)是一种与感染性心内膜炎和结直肠癌(CRC)相关的革兰氏阳性细菌。Sgg具有允许细菌在结直肠肿瘤微环境中茁壮成长的特征,并进一步推进结直肠癌的发展以促进其存活。Sgg含有3根毛,通过期变促进结肠细胞粘附和易位。Sgg还含有胆盐水解酶和一种被称为没食子素的细菌素,其在胆汁酸中的活性显著增加,这有助于其在富含胆汁酸的腺瘤性结直肠微环境中生长。Sgg也利用肿瘤代谢物作为能量来源。Sgg还具有单宁酶,其代谢没食子单宁作为碳源,降低单宁的抗凋亡作用,推动结直肠癌的进展。Sgg还通过尚未完全阐明的机制干扰多种致癌细胞信号通路,包括Wnt/β-catenin通路。增加的β-catenin信号也通过增加细胞外基质的表达增强粘附,并通过下调根尖胆汁酸转运体增加管腔内胆汁酸浓度。最后,Sgg诱导CRC细胞中有毒底物的生物转化,导致有毒中间体和DNA加合物的形成,促进CRC的进一步进展。
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