Objective Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD.
Design The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples.
Results ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients.
Conclusion These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.
- intestinal microbiology
- inflammatory bowel disease
- antibacterial peptide
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DS, RB and WZ contributed equally.
Contributors DS, RB and WZ share co-first authorship. DS, JS and ZX conceived the project. DS, RB and ZY performed the mouse experiments. DS and RB did bacterial 16S rDNA high-throughput sequencing. DS and YL conducted the bacteriology experiments. G-fH, WZ, ST, XG and LL provided essential materials and analysed the clinical samples. DS and JS wrote the original draft. JS, CL, G-fH and ZX wrote and reviewed the final version of the text. JS and ZX supervised the study.
Funding This study was supported by the following grants: National Natural Foundation of China (No. 81790631, No. 31770867, No. 31570786, No. 81602557, No. 81800474 and No. 31741026); Zhejiang Provincial Natural Science Foundation of China (No. LY18H030006 and No. LY17H160021); Fundamental Research Funds for the Central Universities (No. 2017FZA7006).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval Ethics approval for these studies involving human samples was obtained from the Ethics Committee of Zhejiang University School of Medicine (#2018–020, 2018 updated). The animal research was performed under the protocol that has been approved by the Medical Experimental Animal Care Commission of Zhejiang University (#12364, 2019 updated).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. The bacterial 16S rDNA sequences were deposited to the sequence read archive. The accession number for the 16S sequencing data reported in this paper is PRJNA559351.
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