Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation

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 inf...

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Main Authors: Junpeng Yao, Xiangyun Yan, Yanqiu Li, Yaoyao Chen, Xianjun Xiao, Siyuan Zhou, Wei Zhang, Lu Wang, Min Chen, Fang Zeng, Ying Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1323877/full
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author Junpeng Yao
Xiangyun Yan
Yanqiu Li
Yaoyao Chen
Xianjun Xiao
Siyuan Zhou
Wei Zhang
Lu Wang
Min Chen
Fang Zeng
Ying Li
author_facet Junpeng Yao
Xiangyun Yan
Yanqiu Li
Yaoyao Chen
Xianjun Xiao
Siyuan Zhou
Wei Zhang
Lu Wang
Min Chen
Fang Zeng
Ying Li
author_sort Junpeng Yao
collection DOAJ
description 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 (miR-205-5p, miR-493-5p, miR-215-5p, miR-184, miR-378c, miR-335-5p, miR-514a-3p, miR-141-3p, and miR-34c-5p) with seven bacterial genera (Oscillibacter, Escherichia.Shigella, UCG.002, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG.010, Eubacterium_ruminantium_group and Megamonas), as evidenced by a co-occurrence network. Further, a comprehensive panel of seven diagnostic biomarkers (Oscillibacter, Escherichia.Shigella, UCG.002, miR-205-5p, miR-493-5p, miR-215-5p, and Lachnospiraceae_NK4A136_group) 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.
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spelling doaj.art-f7cfc18b7e704db0a6e681cd2af97b6e2024-01-11T05:09:44ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011410.3389/fmicb.2023.13238771323877Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipationJunpeng Yao0Xiangyun Yan1Yanqiu Li2Yaoyao Chen3Xianjun Xiao4Siyuan Zhou5Wei Zhang6Lu Wang7Min Chen8Fang Zeng9Ying Li10Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaSchool of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaTeaching Affairs Office, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaDepartment of Colorectal Disease, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaWhile 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 (miR-205-5p, miR-493-5p, miR-215-5p, miR-184, miR-378c, miR-335-5p, miR-514a-3p, miR-141-3p, and miR-34c-5p) with seven bacterial genera (Oscillibacter, Escherichia.Shigella, UCG.002, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG.010, Eubacterium_ruminantium_group and Megamonas), as evidenced by a co-occurrence network. Further, a comprehensive panel of seven diagnostic biomarkers (Oscillibacter, Escherichia.Shigella, UCG.002, miR-205-5p, miR-493-5p, miR-215-5p, and Lachnospiraceae_NK4A136_group) 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1323877/fullfunctional constipationgut microbiotamicroRNA16S rRNAmicroRNA sequencing
spellingShingle Junpeng Yao
Xiangyun Yan
Yanqiu Li
Yaoyao Chen
Xianjun Xiao
Siyuan Zhou
Wei Zhang
Lu Wang
Min Chen
Fang Zeng
Ying Li
Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
Frontiers in Microbiology
functional constipation
gut microbiota
microRNA
16S rRNA
microRNA sequencing
title Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
title_full Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
title_fullStr Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
title_full_unstemmed Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
title_short Altered gut microbial profile is associated with differentially expressed fecal microRNAs in patients with functional constipation
title_sort altered gut microbial profile is associated with differentially expressed fecal micrornas in patients with functional constipation
topic functional constipation
gut microbiota
microRNA
16S rRNA
microRNA sequencing
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1323877/full
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