Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection
Abstract Background Bloodstream infection (BSI) is a serious hematopoietic stem cell transplantation (HSCT) complication. The intestinal microbiome regulates host metabolism and maintains intestinal homeostasis. Thus, the impact of microbiome on HSCT patients with BSI is essential. Methods Stool and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04068-9 |
| _version_ | 1797853603402088448 |
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| author | Guankun Yin Yifan Guo Qi Ding Shuai Ma Fengning Chen Qi Wang Hongbin Chen Hui Wang |
| author_facet | Guankun Yin Yifan Guo Qi Ding Shuai Ma Fengning Chen Qi Wang Hongbin Chen Hui Wang |
| author_sort | Guankun Yin |
| collection | DOAJ |
| description | Abstract Background Bloodstream infection (BSI) is a serious hematopoietic stem cell transplantation (HSCT) complication. The intestinal microbiome regulates host metabolism and maintains intestinal homeostasis. Thus, the impact of microbiome on HSCT patients with BSI is essential. Methods Stool and serum specimens of HSCT patients were prospectively collected from the pretransplant conditioning period till 4 months after transplantation. Specimens of 16 patients without BSI and 21 patients before BSI onset were screened for omics study using 16S rRNA gene sequencing and untargeted metabolomics. The predictive infection model was constructed using LASSO and the logistic regression algorithm. The correlation and influence of microbiome and metabolism were examined in mouse and Caco-2 cell monolayer models. Results The microbial diversity and abundance of Lactobacillaceae were remarkably reduced, but the abundance of Enterobacteriaceae (especially Klebsiella quasipneumoniae) was significantly increased in the BSI group before onset, compared with the non-BSI group. The family score of microbiome features (Enterobacteriaceae and Butyricicoccaceae) could highly predict BSI (AUC = 0.879). The serum metabolomic analysis showed that 16 differential metabolites were mainly enriched in the primary bile acid biosynthesis pathway, and the level of chenodeoxycholic acid (CDCA) was positively correlated with the abundance of K. quasipneumoniae (R = 0.406, P = 0.006). The results of mouse experiments confirmed that three serum primary bile acids levels (cholic acid, isoCDCA and ursocholic acid), the mRNA expression levels of bile acid farnesol X receptor gene and apical sodium-dependent bile acid transporter gene in K. quasipneumoniae colonized mice were significantly higher than those in non-colonized mice. The intestinal villus height, crypt depth, and the mRNA expression level of tight junction protein claudin-1 gene in K. quasipneumoniae intestinal colonized mice were significantly lower than those in non-colonized mice. In vitro, K. quasipneumoniae increased the clearance of FITC-dextran by Caco-2 cell monolayer. Conclusions This study demonstrated that the intestinal opportunistic pathogen, K. quasipneumoniae, was increased in HSCT patients before BSI onset, causing increased serum primary bile acids. The colonization of K. quasipneumoniae in mice intestines could lead to mucosal integrity damage. The intestinal microbiome features of HSCT patients were highly predictive of BSI and could be further used as potential biomarkers. |
| first_indexed | 2024-04-09T19:53:24Z |
| format | Article |
| id | doaj.art-afd5f99aa0e640dc83e5ab0963e454ab |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T19:53:24Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-afd5f99aa0e640dc83e5ab0963e454ab2023-04-03T05:39:00ZengBMCJournal of Translational Medicine1479-58762023-03-0121111510.1186/s12967-023-04068-9Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infectionGuankun Yin0Yifan Guo1Qi Ding2Shuai Ma3Fengning Chen4Qi Wang5Hongbin Chen6Hui Wang7Department of Clinical Laboratory, Peking University People’s HospitalDepartment of Clinical Laboratory, Peking University People’s HospitalDepartment of Clinical Laboratory, Peking University People’s HospitalInstitute of Medical Technology, Peking University Health Science CenterInstitute of Medical Technology, Peking University Health Science CenterDepartment of Clinical Laboratory, Peking University People’s HospitalDepartment of Clinical Laboratory, Peking University People’s HospitalDepartment of Clinical Laboratory, Peking University People’s HospitalAbstract Background Bloodstream infection (BSI) is a serious hematopoietic stem cell transplantation (HSCT) complication. The intestinal microbiome regulates host metabolism and maintains intestinal homeostasis. Thus, the impact of microbiome on HSCT patients with BSI is essential. Methods Stool and serum specimens of HSCT patients were prospectively collected from the pretransplant conditioning period till 4 months after transplantation. Specimens of 16 patients without BSI and 21 patients before BSI onset were screened for omics study using 16S rRNA gene sequencing and untargeted metabolomics. The predictive infection model was constructed using LASSO and the logistic regression algorithm. The correlation and influence of microbiome and metabolism were examined in mouse and Caco-2 cell monolayer models. Results The microbial diversity and abundance of Lactobacillaceae were remarkably reduced, but the abundance of Enterobacteriaceae (especially Klebsiella quasipneumoniae) was significantly increased in the BSI group before onset, compared with the non-BSI group. The family score of microbiome features (Enterobacteriaceae and Butyricicoccaceae) could highly predict BSI (AUC = 0.879). The serum metabolomic analysis showed that 16 differential metabolites were mainly enriched in the primary bile acid biosynthesis pathway, and the level of chenodeoxycholic acid (CDCA) was positively correlated with the abundance of K. quasipneumoniae (R = 0.406, P = 0.006). The results of mouse experiments confirmed that three serum primary bile acids levels (cholic acid, isoCDCA and ursocholic acid), the mRNA expression levels of bile acid farnesol X receptor gene and apical sodium-dependent bile acid transporter gene in K. quasipneumoniae colonized mice were significantly higher than those in non-colonized mice. The intestinal villus height, crypt depth, and the mRNA expression level of tight junction protein claudin-1 gene in K. quasipneumoniae intestinal colonized mice were significantly lower than those in non-colonized mice. In vitro, K. quasipneumoniae increased the clearance of FITC-dextran by Caco-2 cell monolayer. Conclusions This study demonstrated that the intestinal opportunistic pathogen, K. quasipneumoniae, was increased in HSCT patients before BSI onset, causing increased serum primary bile acids. The colonization of K. quasipneumoniae in mice intestines could lead to mucosal integrity damage. The intestinal microbiome features of HSCT patients were highly predictive of BSI and could be further used as potential biomarkers.https://doi.org/10.1186/s12967-023-04068-9Hematopoietic stem cell transplantationBloodstream infectionIntestinal microbiomeKlebsiella quasipneumonaeSerum metabolomePrimary bile acid |
| spellingShingle | Guankun Yin Yifan Guo Qi Ding Shuai Ma Fengning Chen Qi Wang Hongbin Chen Hui Wang Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection Journal of Translational Medicine Hematopoietic stem cell transplantation Bloodstream infection Intestinal microbiome Klebsiella quasipneumonae Serum metabolome Primary bile acid |
| title | Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| title_full | Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| title_fullStr | Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| title_full_unstemmed | Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| title_short | Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| title_sort | klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection |
| topic | Hematopoietic stem cell transplantation Bloodstream infection Intestinal microbiome Klebsiella quasipneumonae Serum metabolome Primary bile acid |
| url | https://doi.org/10.1186/s12967-023-04068-9 |
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