Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis

Chen Wentao; Wang Xiaoxiang; Zheng Wenlian; Zhang Weiqiang; Mao Lujia; Zhuo Jianan; Zhou Sitong; Yang Ronghua

doi:10.3760/cma.j.cn501225-20231129-00215

Volume 40 Issue 4

Apr. 2024

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Article Navigation > CHINESE JOURNAL OF BURNS AND WOUNDS > 2024 > 40(4): 333-341

Chen WT,Wang XX,Zheng WL,et al.Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis[J].Chin J Burns Wounds,2024,40(4):333-341.DOI: 10.3760/cma.j.cn501225-20231129-00215.

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Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis

doi: 10.3760/cma.j.cn501225-20231129-00215

1.
The First Clinical College of Medicine, Guangdong Medical University, Zhanjiang 524023, China
2.
Department of Burn Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510030, China
3.
Department of Burn and Plastic Surgery, the First People's Hospital of Shaoguan, Shaoguan 512000, China
4.
Department of Burn Plastic Surgery and Wound Repair, Guangzhou First People's Hospital, Guangzhou 510180, China
5.
Dermatology Department, Foshan First People's Hospital, Foshan 528000, China

Funds:

General Program of National Natural Science Foundation of China 82272276

Chongqing Traditional Chinese Medicine Innovation Team Project 2023090006KJZX2022WJW008

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Corresponding author: Yang Ronghua, Email: 21720091@qq.com
Received Date: 2023-11-29

Abstract

Abstract

Objective To investigate the causality between intestinal flora and hypertrophic scars (HS) of human. Methods This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.
- Mendelian randomization analysis,
- Databases, genetic,
- Causality,
- Gastrointestinal microbiome,
- Hyperplastic scar

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Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis

doi: 10.3760/cma.j.cn501225-20231129-00215

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Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis

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