Yao Junpeng, Yan Xiangyun, Li Yanqiu, Chen Yaoyao, Xiao Xianjun, Zhou Siyuan, Zhang Wei, Wang Lu, Chen Min, Zeng Fang, Li Ying
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Microbiol. 2024 Jan 11;14:1323877. doi: 10.3389/fmicb.2023.1323877. eCollection 2023.
While dysbiosis within the intestinal ecosystem has been associated with functional constipation (FC), the mechanisms underlying the interactions between FC and the microbiome remain poorly elucidated. Recent investigations suggested that host microRNAs (miRNAs) can modulate bacterial growth and influence the composition of the gut microbiome. To explore the connection between gut microbiota and fecal miRNAs in FC patients, we initially employed 16S rRNA sequencing to assess the gut microbial landscape in 30 FC patients and 30 healthy controls (HCs). The α-diversity within the FC group exhibited some alterations, and the β-diversity significantly differed, signifying distinctive variations in gut microbiota composition between FC patients and HCs. Subsequently, we identified 44 differentially expressed (DE) miRNAs in feces from FC patients and HCs. Through correlation analysis between DE miRNAs and FC-associated microbiota, we detected an interaction involving nine DE miRNAs (, , , , , , , , and ) with seven bacterial genera (, , , , , and ), as evidenced by a co-occurrence network. Further, a comprehensive panel of seven diagnostic biomarkers (, , , , , , and ) demonstrated robust discriminatory capacity in predicting FC status when integrated into a random forest model (AUC = 0.832, 95% CI: 65.73-98.88). Microbiomes correlating with DE miRNAs exhibited enrichment in distinct predicted metabolic categories. Moreover, miRNAs correlated with FC-associated bacteria were found to be enriched in signaling pathways linked to colonic contractility, including Axon guidance, PI3K-Akt signaling pathway, MAPK signaling pathway, and Hippo signaling pathway. Our study offers a comprehensive insight into the global relationship between microbiota and fecal miRNAs in the context of FC, presenting potential targets for further experimental validation and therapeutic interventions.
虽然肠道生态系统内的生态失调与功能性便秘（FC）有关，但FC与微生物组之间相互作用的潜在机制仍未得到充分阐明。最近的研究表明，宿主微小RNA（miRNA）可以调节细菌生长并影响肠道微生物组的组成。为了探索FC患者肠道微生物群与粪便miRNA之间的联系，我们首先采用16S rRNA测序来评估30例FC患者和30例健康对照（HC）的肠道微生物景观。FC组内的α多样性表现出一些改变，β多样性有显著差异，这表明FC患者和HC之间肠道微生物群组成存在明显差异。随后，我们在FC患者和HC的粪便中鉴定出44种差异表达（DE）的miRNA。通过DE miRNA与FC相关微生物群之间的相关性分析，我们检测到9种DE miRNA（， ， ， ， ， ， ， ，和 ）与7个细菌属（， ， ， ， ， 和 ）之间存在相互作用，共现网络证明了这一点。此外，由7种诊断生物标志物（， ， ， ， ， ，和 ）组成的综合面板在整合到随机森林模型中时，在预测FC状态方面表现出强大的区分能力（AUC = 0.832，95% CI：65.73 - 98.88）。与DE miRNA相关的微生物群在不同的预测代谢类别中表现出富集。此外，发现与FC相关细菌相关的miRNA在与结肠收缩性相关的信号通路中富集，包括轴突导向、PI3K - Akt信号通路、MAPK信号通路和Hippo信号通路。我们的研究全面深入地了解了FC背景下微生物群与粪便miRNA之间的整体关系，为进一步的实验验证和治疗干预提供了潜在靶点。
