宏基因组学和靶向代谢组学分析揭示了结直肠癌和 2 型糖尿病患者肠道微生物群的不同表型。
Metagenomic and targeted metabolomic analyses reveal distinct phenotypes of the gut microbiota in patients with colorectal cancer and type 2 diabetes mellitus.
机构信息
Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China.
Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing 100144, China.
出版信息
Chin Med J (Engl). 2023 Dec 5;136(23):2847-2856. doi: 10.1097/CM9.0000000000002421.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear.
METHODS
We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups.
RESULTS
Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga .
CONCLUSIONS
Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
背景
2 型糖尿病（T2DM）是结直肠癌（CRC）的独立危险因素，同时患有 CRC 和 T2DM 的患者的生存状况更差。人类肠道微生物群（GM）分别与 CRC 和 T2DM 的发展有关。然而，CRC 和 T2DM 患者的 GM 特征尚不清楚。
方法
我们对 36 个样本进行了粪便宏基因组和靶向代谢组学研究，这些样本来自同时患有 T2DM 的 CRC 患者（DCRC 组，n = 12）、无糖尿病的 CRC 患者（CRC 组，n = 12）和健康对照者（Health 组，n = 12）。我们分析了粪便微生物组，基于 DCRC 患者的宏基因组学对其组成和功能进行了特征描述，并检测了所有粪便样本中的短链脂肪酸（SCFAs）和胆汁酸（BAs）水平。最后，我们对不同组之间差异细菌和代谢物进行了相关性分析。
结果
与 CRC 组相比，LefSe 分析显示 DCRC 组存在特定的 GM 群落，包括 Eggerthella 、Hungatella 、Peptostreptococcus 和 Parvimonas 的丰度增加，以及 Butyricicoccus 、Lactobacillus 和 Paraprevotella 的丰度降低。代谢组学分析结果表明，DCRC 组的丁酸水平较低，但脱氧胆酸和 12-酮石胆酸水平高于其他组（P < 0.05）。相关性分析显示，DCRC 组的优势细菌丰度（Parvimonas 、Desulfurispora 、Sebaldella 和 Veillonellales 等）与丁酸、去氧胆酸、熊去氧胆酸、甘氨胆酸、鹅去氧胆酸和胆酸甘氨酸呈负相关。然而，大多数低等细菌的丰度与这些代谢酸水平呈正相关，包括 Faecalibacterium 、Thermococci 和 Cellulophaga 。
结论
与非糖尿病 CRC 患者相比，同时患有 T2DM 的 CRC 患者存在独特的粪便微生物组特征。GM 组成和 SCFAs 及次级 BAs 水平的改变可能会促进 CRC 的发展。
Zotero 插件