Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study

Kaikai Xue; Guojian Zhang; Zihao Li; Xiangtao Zeng; Zi Li; Fulin Wang; Xingxing Zhang; Cai Lin; Cong Mao

doi:10.3389/fmicb.2024.1345717

Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study

Front Microbiol. 2024 Mar 21:15:1345717. doi: 10.3389/fmicb.2024.1345717. eCollection 2024.

Authors

Kaikai Xue^{1

2}, Guojian Zhang^{1

2}, Zihao Li^{1

2}, Xiangtao Zeng^{1

2}, Zi Li¹, Fulin Wang¹, Xingxing Zhang³, Cai Lin², Cong Mao¹

Affiliations

¹ Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Burn, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established that an imbalance in the composition of gut microbes, termed microbial dysbiosis, can initiate the progression of various diseases through the intricate interplay between gut microbiota and the host. However, the precise nature of the causal link between gut microbiota and hypertrophic scarring remains uncertain. In this study, after compiling summary data from genome-wide association studies (GWAS) involving 418 instances of gut microbiota and hypertrophic scarring, we conducted a bidirectional Mendelian randomization (MR) to investigate the potential existence of a causal relationship between gut microbiota and the development of hypertrophic scar and to discern the directionality of causation. By utilizing MR analysis, we identified seven causal associations between gut microbiome and hypertrophic scarring, involving one positive and six negative causal directions. Among them, Intestinimonas, Ruminococcus2, Barnesiella, Dorea, Desulfovibrio piger, and Ruminococcus torques act as protective factors against hypertrophic scarring, while Eubacterium rectale suggests a potential role as a risk factor for hypertrophic scars. Additionally, sensitivity analyses of these results revealed no indications of heterogeneity or pleiotropy. The findings of our MR study suggest a potential causative link between gut microbiota and hypertrophic scarring, opening up new ways for future mechanistic research and the exploration of nanobiotechnology therapies for skin disorders.

Keywords: Firmicutes; GWAS; Mendelian randomization; gut microbiota; hypertrophic scar.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We sincerely thank for the financial support of Zhejiang Provincial Basic Public Welfare Research Program of China (grant no. LTGY23H150004, LY22H150004, LGD22H070001), Key Science and Technology Program of Zhejiang Province (grant no. 2023C0317), Medical Health Science and Technology Project of Zhejiang Province (grant no. 2023KY146), Wenzhou Science and Technology Bureau Project of China (grant no. Y2023100).