Effects of USP25 knockout on the gut microbial diversity and composition in mice

Abstract Background The gut microbiota plays a crucial role in host health. Recent study revealed that ubiquitin-specific protease 25 (USP25) deficiency affected colonic immune responses and resistance to certain bacterial infection. This study aimed to investigate the impact of USP25 gene deletion...

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Main Authors: Jinqiu Li, Zhonghui Chen, Xingchen Yan, Qizhou Chen, Cirong Chen, Huan Liu, Jianlin Shen
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Microbiology
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Online Access:https://doi.org/10.1186/s12866-025-04035-y
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author Jinqiu Li
Zhonghui Chen
Xingchen Yan
Qizhou Chen
Cirong Chen
Huan Liu
Jianlin Shen
author_facet Jinqiu Li
Zhonghui Chen
Xingchen Yan
Qizhou Chen
Cirong Chen
Huan Liu
Jianlin Shen
author_sort Jinqiu Li
collection DOAJ
description Abstract Background The gut microbiota plays a crucial role in host health. Recent study revealed that ubiquitin-specific protease 25 (USP25) deficiency affected colonic immune responses and resistance to certain bacterial infection. This study aimed to investigate the impact of USP25 gene deletion on the gut microbiota of mice, utilizing 16 S rRNA amplicon sequencing and metagenomic sequencing to provide a comprehensive analysis of microbial diversity, composition and functional characteristics. Methods We collected fecal samples from 10 wild type (WT) C57BL/6J mice and 10 USP25−/− mice (C57BL/6J-Usp25em1cyagen) for 16 S rRNA amplicon sequencing. Subsequently, the 6 of the 20 samples underwent further analysis using metagenomic sequencing. Results Our results revealed significant differences in the gut microbiota between USP25 knockout (KO) mice and wild-type (WT) controls, with KO mice exhibiting 1,858 unique amplicon sequence variants (ASVs) compared to 1,723 in WT mice. Notably, the KO group displayed a higher tendency for biofilm formation and a greater proportion of gram-negative bacteria, while the WT group demonstrated enhanced stress tolerance and a higher presence of gram-positive bacteria. Functional prediction analyses indicated an increase in antibiotic resistance genes in the KO mice, particularly for tetracycline, cephalosporin, and sulfonamides, suggesting a potential risk for clinical antibiotic treatment efficacy. Moreover, KEGG pathway enrichment analysis revealed significant enrichment for fructose and mannose metabolism, streptomycin biosynthesis in the KO group. Furthermore, an increase in protective microbes alongside a decrease in potential pathogens in the KO microbiota hinted at altered immune responses due to USP25 deletion. Conclusion Our findings elucidate the essential role of USP25 in modulating gut microbiota composition and function, providing insights for future therapeutic strategies targeting gut microbiota in disease contexts. Clinical trail number Not applicable.
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spelling doaj-art-1feb8e822e3f44afba28a135d2abeaca2025-08-20T02:34:17ZengBMCBMC Microbiology1471-21802025-05-0125111410.1186/s12866-025-04035-yEffects of USP25 knockout on the gut microbial diversity and composition in miceJinqiu Li0Zhonghui Chen1Xingchen Yan2Qizhou Chen3Cirong Chen4Huan Liu5Jianlin Shen6Central Laboratory, Affiliated Hospital of Putian University, Putian UniversityCentral Laboratory, Affiliated Hospital of Putian University, Putian UniversityGuangdong Academy of Sciences, Guangdong-Hong Kong Joint Laboratory of Modern Surface Engineering Technology, Guangdong Provincial Key Laboratory of Modern Surface Engineering TechnologyPharmaceutical and Medical Technology College, Putian UniversityPharmaceutical and Medical Technology College, Putian UniversityDepartment of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityCentral Laboratory, Affiliated Hospital of Putian University, Putian UniversityAbstract Background The gut microbiota plays a crucial role in host health. Recent study revealed that ubiquitin-specific protease 25 (USP25) deficiency affected colonic immune responses and resistance to certain bacterial infection. This study aimed to investigate the impact of USP25 gene deletion on the gut microbiota of mice, utilizing 16 S rRNA amplicon sequencing and metagenomic sequencing to provide a comprehensive analysis of microbial diversity, composition and functional characteristics. Methods We collected fecal samples from 10 wild type (WT) C57BL/6J mice and 10 USP25−/− mice (C57BL/6J-Usp25em1cyagen) for 16 S rRNA amplicon sequencing. Subsequently, the 6 of the 20 samples underwent further analysis using metagenomic sequencing. Results Our results revealed significant differences in the gut microbiota between USP25 knockout (KO) mice and wild-type (WT) controls, with KO mice exhibiting 1,858 unique amplicon sequence variants (ASVs) compared to 1,723 in WT mice. Notably, the KO group displayed a higher tendency for biofilm formation and a greater proportion of gram-negative bacteria, while the WT group demonstrated enhanced stress tolerance and a higher presence of gram-positive bacteria. Functional prediction analyses indicated an increase in antibiotic resistance genes in the KO mice, particularly for tetracycline, cephalosporin, and sulfonamides, suggesting a potential risk for clinical antibiotic treatment efficacy. Moreover, KEGG pathway enrichment analysis revealed significant enrichment for fructose and mannose metabolism, streptomycin biosynthesis in the KO group. Furthermore, an increase in protective microbes alongside a decrease in potential pathogens in the KO microbiota hinted at altered immune responses due to USP25 deletion. Conclusion Our findings elucidate the essential role of USP25 in modulating gut microbiota composition and function, providing insights for future therapeutic strategies targeting gut microbiota in disease contexts. Clinical trail number Not applicable.https://doi.org/10.1186/s12866-025-04035-yUSP25Gut microbiota16S rRNA sequencingMetagenomic sequencingAntibiotic resistanceHost-microbe interactions
spellingShingle Jinqiu Li
Zhonghui Chen
Xingchen Yan
Qizhou Chen
Cirong Chen
Huan Liu
Jianlin Shen
Effects of USP25 knockout on the gut microbial diversity and composition in mice
BMC Microbiology
USP25
Gut microbiota
16S rRNA sequencing
Metagenomic sequencing
Antibiotic resistance
Host-microbe interactions
title Effects of USP25 knockout on the gut microbial diversity and composition in mice
title_full Effects of USP25 knockout on the gut microbial diversity and composition in mice
title_fullStr Effects of USP25 knockout on the gut microbial diversity and composition in mice
title_full_unstemmed Effects of USP25 knockout on the gut microbial diversity and composition in mice
title_short Effects of USP25 knockout on the gut microbial diversity and composition in mice
title_sort effects of usp25 knockout on the gut microbial diversity and composition in mice
topic USP25
Gut microbiota
16S rRNA sequencing
Metagenomic sequencing
Antibiotic resistance
Host-microbe interactions
url https://doi.org/10.1186/s12866-025-04035-y
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