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. 2021 Jan-Dec;13(1):1-18.
doi: 10.1080/19490976.2020.1865708.

Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn's disease (VSports最新版本)

Yizhong Wang  1   2 , Xuefeng Gao  3 , Xinyue Zhang  1 , Fangfei Xiao  1 , Hui Hu  1 , Xiaolu Li  1 , Fang Dong  1 , Mingming Sun  4 , Yongmei Xiao  1 , Ting Ge  1 , Dan Li  1 , Guangjun Yu  2 , Zhanju Liu  4 , Ting Zhang  1   2
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"V体育平台登录" Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn's disease

Yizhong Wang et al. Gut Microbes. 2021 Jan-Dec.

"VSports app下载" Abstract

Gut microbial dysbiosis and altered metabonomics have been implicated in the pathogenesis of Crohn's disease (CD). The aim of our study was to characterize the gut microbiome structure and metabolic activities in pediatric CD patients with different clinical outcomes after infliximab (IFX) therapy VSports手机版. Fecal samples were collected from 20 healthy children and 29 newly diagnosed pediatric CD patients. 16S rRNA/ITS2 gene sequencing and targeted metabolomics analysis were applied to profile the gut bacterial microbiome, mycobiome, and metabolome, respectively. Pediatric CD patients exhibited lower relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Faecalibacterium, Clostridium clusters IV and XIVb, Roseburia, and Ruminococcus, which were correlated with reduced fecal levels of SCFAs. Decreased unconjugated bile acids (BAs) pool size and a lower unconjugated/conjugated BAs ratio were associated with reduced relative abundances of Bifidobacterium and Clostridium clusters IV and XIVb which contain bile salt hydrolases (BSH) genes. IFX treatment enriched the BSH-producing bacteria in CD subjects, which may explain a decreased level of conjugated BAs and an increase in unconjugated BAs as well as the unconjugated/conjugated BAs ratio. Furthermore, a sustained response (SR) of IFX therapy was associated with higher abundances of Methylobacterium, Sphingomonas, Staphylococcus, and Streptococcus, and higher fecal concentrations of amino acids, including L-aspartic acid, linoleic acid, and L-lactic acid at baseline. Our study suggests that the effects of IFX might be partially mediated by enriching bacteria taxa that producing SCFAs and BSH thereby inhibiting inflammation and restoring the BA metabolism. Some fecal bacteria and metabolites may be predictive of outcomes of IFX therapy for pediatric CD patients. .

Keywords: Children; Crohn’s disease; gut microbiome; infliximab; metabolome. V体育安卓版.

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Figures

Figure 1.
Figure 1.
Altered fecal microbiome biodiversity and composition in the pediatric CD patients. Beta diversity of bacterial (a) and fungal (c) microbiome. PCoA of Bray–Curtis distance with each sample colored according to the phenotype. PC1 and PC2 represent the top two principal coordinates that captured most of the diversity. The fraction of diversity captured by the coordinate is given as a percentage. Groups were compared using PERMANOVA method. Boxplots showing the significantly different bacterial genera (b) and fungal genera (d), and their relative abundances (in log2(CSS)) in HS and CD patients before IFX treatment. Significance is determined by using Wilcoxon rank-sum test, with *P < .05, **P < .01, ***P < .001, and #FDR<0.05. CD, Crohn’s disease; HS, healthy subjects; PCoA, principal coordinate analysis
Figure 2.
Figure 2.
Altered fecal metabolomics in the CD patients compared with the HS. (a) Heat map showing the top 50 metabolites that different between the CD and HS, and the significance was determined by using Wilcoxon rank-sum test (***P < .001). (b) Supervised clustering of fecal metabolites using sPLS-DA. (c) The top metabolites ranked by VIP scores. (d–g) ROC analysis of potential biomarkers (AUC>0.9) for differentiating the CD patients from HS. CD, Crohn’s disease; HS, healthy subjects; sPLS-DA, sparse partial least squares discriminant analysis; VIP, variable importance in projection
Figure 3.
Figure 3.
Potentially mechanistic associations between CD-linked microbes and metabolites. Network of the top 100 pairwise metabolite-microbe correlations. Metabolites and microbes are represented as red circles and blue ovals. Their positive and negative correlations are indicated using red and green color, respectively. Differential metabolites and bacteria between the CD and HS at baseline (Mann–Whitney U test, P < .01) were selected for the Spearman correlation coefficients. Coefficient values R ≤ −0.5 and ≥ 0.5 with P value < .01 were considered statistically significant, and were plotted in network. CD, Crohn’s disease; HS, healthy subjects
Figure 4.
Figure 4.
Changes in the fecal microbiome biodiversity and composition in the pediatric CD patients after IFX treatment. Beta diversity of bacterial (a) and fungal microbiome (c). PCoA of Bray–Curtis distance with each sample colored according to the phenotype. PC1 and PC2 represent the top two principal coordinates that captured most of the diversity. The fraction of diversity captured by the coordinate is given as a percentage. Groups were compared using PERMANOVA method. Boxplots showing the significantly different bacterial genera (b) and fungal genera (d) in the CD patients before and after IFX treatment. The relative abundances were shown in log2(CSS). Significance is determined by using Wilcoxon rank-sum test, with *P < .05. CD, Crohn’s disease; IFX, infliximab; NSR, non-sustained response; PCoA, principal coordinate analysis; SR, sustained response
Figure 5.
Figure 5.
Fecal metabolomics changes in the pediatric CD patients after IFX treatment. (a) Heat map showing the top 40 metabolites that with significantly changed (T-test, P < .05) in the pediatric CD patients after IFX treatment. (b) Supervised clustering of fecal metabolites using sPLS-DA; (c) The top metabolites ranked by VIP scores. CD, Crohn’s disease; IFX, infliximab; sPLS-DA, sparse partial least squares discriminant analysis; VIP, variable importance in projection
Figure 6.
Figure 6.
Bacterial and fungal genera correlate with outcome of the pediatric CD patients with IFX treatment. Boxplots showing the significantly different bacterial genera between the SR and NSR patients before (a) and after IFX (b) treatment, and the significantly different fungal genera between the SR and NSR patients after IFX treatment (c). The relative abundances were shown in log2(CSS). Significance is determined by using Wilcoxon rank-sum test (FDR<0.5), with *P < .05 and **P < .01. CD, Crohn’s disease; IFX, infliximab; NSR, non-sustained response; SR, sustained response
Figure 7..
Figure 7..
Distinct metabolic profiles are associated with different outcomes before and after IFX treatment. Heat maps showing the top 50 metabolites that different between SR and NSR at baseline (a) and after IFX treatment (d). Significance is determined by using Wilcoxon rank-sum test, with *P < .05. Supervised clustering of fecal metabolites using sPLS-DA in samples of SR and NSR at baseline (b) and after IFX treatment (e). The top metabolites ranked by VIP scores in samples of SR and NSR at baseline (c) and after IFX treatment (f). IFX, infliximab; NSR, non-sustained response; SR, sustained response; sPLS-DA, sparse partial least squares discriminant analysis; VIP, variable importance in projection
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