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结直肠癌中的息肉与肿瘤微环境重编程:来自黏膜微生物组与代谢物相互作用的见解

Polyp and tumor microenvironment reprogramming in colorectal cancer: insights from mucosal bacteriome and metabolite crosstalk.

作者信息

Feizi Hadi, Kafil Hossein Samadi, Plotnikov Andrey, Kataev Vladimir, Balkin Alexander, Filonchikova Ekaterina, Rezaee Mohammad Ahangarzadeh, Ghotaslou Reza, Sadrkabir Mohammad, Kadkhoda Hiva, Kamounah Fadhil S, Nikitin Sergei

机构信息

Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Microbiology, Aalinasab Hospital, Social Security Organization, Tabriz, Iran.

出版信息

Ann Clin Microbiol Antimicrob. 2025 Jan 29;24(1):9. doi: 10.1186/s12941-025-00777-9.

DOI:10.1186/s12941-025-00777-9
PMID:39881353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11780822/
Abstract

BACKGROUND

Highly frequent colorectal cancer (CRC) is predicted to have 3.2 million novel cases by 2040. Tumor microenvironment (TME) bacteriome and metabolites are proposed to be involved in CRC development. In this regard, we aimed to investigate the bacteriome and metabolites of healthy, adenomatous polyp, and CRC tissues.

METHODS

Sixty samples including healthy (H), adenomatous polyps (AP), adenomatous polyps-adjacent (APA), cancer tumor (CT), and cancer tumor-adjacent (CA) tissues were collected and analyzed by 16 S rRNA sequencing and H NMR spectroscopy.

RESULTS

Our results revealed that the bacteriome and metabolites of the H, AP, and CT groups were significantly different. We observed that the Lachnospiraceae family depleted concomitant with acetoacetate and beta-hydroxybutyric acid (BHB) accumulations in the AP tissues. In addition, some bacterial species including Gemella morbillorum, and Morganella morganii were enriched in the AP compared to the H group. Furthermore, fumarate was accumulated concomitant to Aeromonas enteropelogenes, Aeromonas veronii, and Fusobacterium nucleatum subsp. animalis increased abundance in the CT compared to the H group.

CONCLUSION

These results proposed that beneficial bacteria including the Lachnospiraceae family depletion cross-talk with acetoacetate and BHB accumulations followed by an increased abundance of driver bacteria including G. morbillorum, and M. morganii may reprogram polyp microenvironment leading to tumor initiation. Consequently, passenger bacteria accumulation like A. enteropelogenes, A.veronii, and F. nucleatum subsp. animalis cross-talking fumarate in the TME may aggravate cancer development. So, knowledge of TME bacteriome and metabolites might help in cancer prevention, early diagnosis, and a good prognosis.

摘要

背景

预计到2040年,结直肠癌(CRC)新发病例将高达320万。肿瘤微环境(TME)中的细菌群落和代谢产物被认为与结直肠癌的发生发展有关。在这方面,我们旨在研究健康组织、腺瘤性息肉组织和结直肠癌组织中的细菌群落和代谢产物。

方法

收集了60份样本,包括健康组织(H)、腺瘤性息肉(AP)、腺瘤性息肉旁组织(APA)、癌组织(CT)和癌旁组织(CA),并通过16S rRNA测序和核磁共振氢谱(H NMR)进行分析。

结果

我们的结果显示,H组、AP组和CT组的细菌群落和代谢产物存在显著差异。我们观察到,在AP组织中,毛螺菌科减少,同时乙酰乙酸和β-羟基丁酸(BHB)积累。此外,与H组相比,一些细菌种类,包括麻疹孪生球菌和摩根氏摩根菌,在AP中富集。此外,与H组相比,产气肠杆菌、维氏气单胞菌和具核梭杆菌亚种动物亚种丰度增加,同时富马酸盐积累。

结论

这些结果表明,有益细菌如毛螺菌科减少与乙酰乙酸和BHB积累相互作用,随后驱动细菌如麻疹孪生球菌和摩根氏摩根菌丰度增加,可能会重新编程息肉微环境,导致肿瘤发生。因此,像产气肠杆菌、维氏气单胞菌和具核梭杆菌亚种动物亚种等过客细菌在TME中与富马酸盐相互作用,可能会加剧癌症发展。所以,了解TME中的细菌群落和代谢产物可能有助于癌症预防、早期诊断和良好预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/89723c82091b/12941_2025_777_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/89723c82091b/12941_2025_777_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/00d76367ce41/12941_2025_777_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/32714d251018/12941_2025_777_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/109f7b64f3a7/12941_2025_777_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/30da1ed78307/12941_2025_777_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/3e74120b967e/12941_2025_777_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/462c74ced4f9/12941_2025_777_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8be/11780822/89723c82091b/12941_2025_777_Fig7_HTML.jpg

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本文引用的文献

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β-hydroxybutyrate restrains colitis-associated tumorigenesis by inhibiting HIF-1α-mediated angiogenesis.β-羟丁酸通过抑制 HIF-1α 介导的血管生成来抑制结肠炎相关肿瘤发生。
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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Identification of taxonomic changes in the fecal bacteriome associated with colorectal polyps and cancer: potential biomarkers for early diagnosis.与结直肠息肉和癌症相关的粪便细菌群落分类学变化的鉴定:早期诊断的潜在生物标志物。
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