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囊性纤维化患者有无结肠腺瘤的肠道微生物组、短链脂肪酸和相关代谢物。

The gut microbiome, short chain fatty acids, and related metabolites in cystic fibrosis patients with and without colonic adenomas.

机构信息

Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Microbiome and Pathogen Genomics Collaborative Center, Columbia University Irving Medical Center, New York, NY, USA.

出版信息

J Cyst Fibros. 2023 Jul;22(4):738-744. doi: 10.1016/j.jcf.2023.01.013. Epub 2023 Jan 28.

DOI:10.1016/j.jcf.2023.01.013
PMID:36717332
Abstract

BACKGROUND

Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas.

METHODS

Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS.

RESULTS

42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas.

CONCLUSIONS

CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.

摘要

背景

囊性纤维化(CF)成人患者结肠癌风险增加。CF 患者肠道内产生短链脂肪酸(SCFA)的细菌减少,尽管尚不清楚这是否与肠道 SCFA 水平和结肠肿瘤的存在有关。本研究旨在比较 CF 患者和非 CF 患者的肠道微生物组和 SCFA 组成,并评估其与结肠腺瘤的相关性。

方法

对接受结肠癌筛查或监测结肠镜检查的 CF 患者和非 CF 患者进行结肠抽吸。通过 16S rRNA V3-V4 测序进行微生物组特征分析。通过 LC-MS 进行 SCFA 和相关代谢物的靶向分析。

结果

共纳入 42 名患者(21 名 CF,21 名对照)。CF 患者的 alpha 多样性显著降低,许多产生 SCFA 的分类群的相对丰度降低。CF 患者的 SCFA 水平没有显著差异,尽管支链脂肪酸(BCFA)和相关代谢物的水平降低。有腺瘤的 CF 患者,而不是有腺瘤的对照患者,Bacteroides fragilis 的相对丰度显著增加。CF 微生物组组成与异戊酸盐浓度和腺瘤的存在显著相关。

结论

CF 患者的肠道微生物组存在明显紊乱,有腺瘤的 CF 患者的 Bacteroides fragilis 相对丰度显著增加,Bacteroides fragilis 是一种已知促进结肠癌的病原体。CF 中发现 BCFA 减少而不是 SCFA 减少。需要进一步研究来评估 B. fragilis 的作用以及 CF 中 BCFA 减少的生物学意义。

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