High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients

There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed...

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Main Authors: Soumaya Kouidhi, Nessrine Souai, Oumaima Zidi, Amor Mosbah, Amel Lakhal, Tarek Ben Othmane, Dorra Belloumi, Farhat Ben Ayed, Elias Asimakis, Panagiota Stathopoulou, Ameur Cherif, George Tsiamis
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/9/9/1845
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author Soumaya Kouidhi
Nessrine Souai
Oumaima Zidi
Amor Mosbah
Amel Lakhal
Tarek Ben Othmane
Dorra Belloumi
Farhat Ben Ayed
Elias Asimakis
Panagiota Stathopoulou
Ameur Cherif
George Tsiamis
author_facet Soumaya Kouidhi
Nessrine Souai
Oumaima Zidi
Amor Mosbah
Amel Lakhal
Tarek Ben Othmane
Dorra Belloumi
Farhat Ben Ayed
Elias Asimakis
Panagiota Stathopoulou
Ameur Cherif
George Tsiamis
author_sort Soumaya Kouidhi
collection DOAJ
description There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (<i>n</i> = 15) and healthy controls (<i>n</i> = 18). The intestinal microbiota was characterized by NGS and gas chromatography–mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the <i>Feacalibacterium</i>, <i>Akkermansia</i>, and <i>Veillonella</i> genera and the <i>Lachnospiraceae</i> family, and an enrichment in multidrug-resistant bacteria belonging to <i>Escherichia</i>, <i>Shigella</i>, and <i>Bacteroides</i>. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of <i>Blautia</i> and a significant mutual-exclusion rate of <i>Citrobacter</i>. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (<i>p</i> < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.
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spelling doaj.art-441623fec4e945409798bca98cfd3b5f2023-11-22T14:17:58ZengMDPI AGMicroorganisms2076-26072021-08-0199184510.3390/microorganisms9091845High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant PatientsSoumaya Kouidhi0Nessrine Souai1Oumaima Zidi2Amor Mosbah3Amel Lakhal4Tarek Ben Othmane5Dorra Belloumi6Farhat Ben Ayed7Elias Asimakis8Panagiota Stathopoulou9Ameur Cherif10George Tsiamis11Laboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, BiotechPole of Sidi Thabet, University of Manouba, Ariana 2020, TunisiaLaboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, BiotechPole of Sidi Thabet, University of Manouba, Ariana 2020, TunisiaLaboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, BiotechPole of Sidi Thabet, University of Manouba, Ariana 2020, TunisiaLaboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, BiotechPole of Sidi Thabet, University of Manouba, Ariana 2020, TunisiaNatioanl Bone Marrow Transplant Center, Tunis 1029, TunisiaNatioanl Bone Marrow Transplant Center, Tunis 1029, TunisiaNatioanl Bone Marrow Transplant Center, Tunis 1029, TunisiaAssociation Tunisienne de Lutte Contre le Cancer (ATCC), Tunis 1938, TunisiaLaboratory of Systems Microbiology and Applied Genomics, Department of Environmental Engineering, University of Patras, 2 Seferi St., 30100 Agrinio, GreeceLaboratory of Systems Microbiology and Applied Genomics, Department of Environmental Engineering, University of Patras, 2 Seferi St., 30100 Agrinio, GreeceLaboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, BiotechPole of Sidi Thabet, University of Manouba, Ariana 2020, TunisiaLaboratory of Systems Microbiology and Applied Genomics, Department of Environmental Engineering, University of Patras, 2 Seferi St., 30100 Agrinio, GreeceThere is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (<i>n</i> = 15) and healthy controls (<i>n</i> = 18). The intestinal microbiota was characterized by NGS and gas chromatography–mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the <i>Feacalibacterium</i>, <i>Akkermansia</i>, and <i>Veillonella</i> genera and the <i>Lachnospiraceae</i> family, and an enrichment in multidrug-resistant bacteria belonging to <i>Escherichia</i>, <i>Shigella</i>, and <i>Bacteroides</i>. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of <i>Blautia</i> and a significant mutual-exclusion rate of <i>Citrobacter</i>. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (<i>p</i> < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.https://www.mdpi.com/2076-2607/9/9/1845allogenic hematopoietic stem cell transplantation (allo-HSCT)microbiotametabolomicsbiomarkers
spellingShingle Soumaya Kouidhi
Nessrine Souai
Oumaima Zidi
Amor Mosbah
Amel Lakhal
Tarek Ben Othmane
Dorra Belloumi
Farhat Ben Ayed
Elias Asimakis
Panagiota Stathopoulou
Ameur Cherif
George Tsiamis
High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
Microorganisms
allogenic hematopoietic stem cell transplantation (allo-HSCT)
microbiota
metabolomics
biomarkers
title High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
title_full High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
title_fullStr High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
title_full_unstemmed High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
title_short High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients
title_sort high throughput analysis reveals changes in gut microbiota and specific fecal metabolomic signature in hematopoietic stem cell transplant patients
topic allogenic hematopoietic stem cell transplantation (allo-HSCT)
microbiota
metabolomics
biomarkers
url https://www.mdpi.com/2076-2607/9/9/1845
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