Abstract
Background
Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with gut microbiota dysbiosis; however, its etiology remains unclear. MicroRNA (miRNA)-microbiome interactions play an essential role in host health and disease.
Methods
To investigate the gut microbiome and host miRNA profiles in colitis, we used a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis (UC) model. Metagenomic sequencing and metabolome profiling were performed to explore typical microbiota and metabolite signatures in colitis, whereas mRNA and miRNA sequencing were used to determine differentially expressed miRNAs and their target genes in the inflamed colon.
Results
A total of 986 miRNAs were identified between the two groups, with 41 upregulated and 21 downregulated miRNAs in colitis mice compared to the control group. Notably, the target genes of these significantly altered miRNAs were primarily enriched in the immune and inflammation-related pathways. Second, LEfSe analysis revealed bacterial biomarkers distinguishing the two groups, with significantly higher levels of commonly encountered pathogens such as Escherichia coli and Shigella flexneri in the UC group, whereas beneficial species such as Bifidobacterium pseudolongum were more abundant in the control group. Microbiota metabolites histamine, N-acetylhistamine, and glycocholic acid were found to be downregulated in colitis mice. Spearman correlation further revealed the potential crosstalk between the microbiota profile and colonic miRNA, revealing the possibility of microbiome–miRNA interactions involved in IBD development.
Conclusions
Our data reveal the relationships between multi-omic features during UC and suggest that targeting specific miRNAs may provide new avenues for the development of effective miRNA-based therapeutics.
Authors contributions
L.M. and C.H. performed the experiments, analyzed the data, prepared the figures, and wrote the manuscript; H.Y. and Q.C. participated in the experiments; W.L. collected samples; Z.W., J.W., and Y.X. contributed to the study concept, design, and revised the manuscript.
Ethics statement
All animal procedures were approved by the Institutional Animal Care and Use Committee of the Zhejiang Academy of Agricultural Sciences (2018ZAASLA20).
Disclosure statement
The authors report no conflict of interest.
Data availability statement
The sequencing data were submitted to the NCBI SRA database using PRJNA795271 and PRJNA795830. The data supporting the findings of this study are available from the corresponding author upon request.