Diabetic foot exacerbates gut mycobiome dysbiosis in adult patients with type 2 diabetes mellitus: revealing diagnostic markers.

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nutrition & Diabetes Pub Date : 2024-09-03 DOI:10.1038/s41387-024-00328-9
Yue Cai, Yiping Li, Yuxin Xiong, Xinqian Geng, Yongbo Kang, Ying Yang
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Abstract

Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment.

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糖尿病足加剧了成年 2 型糖尿病患者肠道菌群失调:揭示诊断标志物。
2 型糖尿病(T2DM)是全球公认的重大健康问题,糖尿病足(DF)被认为是一种严重的长期并发症,可导致组织坏死或截肢。霉菌生物群是肠道微生物组中的一个多细胞真核生物群,发现霉菌生物群对内分泌失调发病的影响具有重要意义。因此,本研究旨在检测真菌菌落生物群的变化,并确定 T2DM 和 T2DM-DF 的潜在生物标志物。研究人员收集了 33 名 T2DM 患者、32 名 T2DM-DF 患者和 32 名无任何健康问题的健康人(HC)的粪便和血液样本。血液样本用于实验室参数分析,而总 DNA 则从粪便样本中提取,并使用 Illumina 18s rRNA 进行测序。研究人员利用生物信息学工具分析了真菌的丰度和多样性,揭示了T2DM组、T2DM-DF组和HC组之间差异表达的真菌种类和特征真菌。首先,在三个组之间观察到了一些实验室参数的明显变化,T2DM 和 T2DM-DF 组之间也存在差异。T2DM组和T2DM-DF组的肠道真菌多样性与HC组有显著差异,但T2DM-DF组的变化更为明显。此外,与 HC 组相比,T2DM 组和 T2DM-DF 组的 Ascomycota 和 Basidiomycota 这两个门类发生了明显变化,Ascomycota 丰度较高,而 Basidiomycota 丰度较低。此外,在物种水平上显示出显著变化的前 15 种真菌包括:与 HC 组相比,T2DM 患者中 Rhodotorula_mucilaginosa 的丰度明显降低;未分类 g_Candida 的丰度显著增加,仅在 T2DM-DF 患者中出现,而在确诊为 T2DM 或 HC 的患者中未出现。第三,采用 KEGG 分析三组患者的酶表达,结果显示,与 T2DM 相比,T2DM-DF 患者的肠道真菌功能发生了更明显的变化。随后,为了准确识别各组的特征真菌,利用随机森林对前 15 种重要真菌进行了排序。值得注意的是,有11种真菌被确定为区分T2DM或T2DM-DF与HC的潜在生物标志物,而有8种真菌可以区分T2DM和T2DM-DF。此外,接收者操作特征曲线(ROC)分析表明,预测结果的准确性有所提高。这些研究结果表明,真菌真菌生物群的变化与 T2DM 和 DF 的进展和并发症密切相关,为诊断和治疗提供了广阔的前景。
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来源期刊
Nutrition & Diabetes
Nutrition & Diabetes ENDOCRINOLOGY & METABOLISM-NUTRITION & DIETETICS
CiteScore
9.20
自引率
0.00%
发文量
50
审稿时长
>12 weeks
期刊介绍: Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.
期刊最新文献
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