Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype

Pamela Vernocchi, Federica Del Chierico, Alessandra Russo, Fabio Majo, Martina Rossitto, Mariacristina Valerio, Luca Casadei, Antonietta La Storia, Francesca De Filippis, Cristiano Rizzo, Cesare Manetti, Paola Paci, Danilo Ercolini, Federico Marini, Ersilia Vita Fiscarelli, Bruno Dallapiccola, Vincenzina Lucidi, Alfredo Miccheli, Lorenza Putignani

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.

OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.

METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.

RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.

CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.

Original languageEnglish
Pages (from-to)e0208171
JournalPLoS One
Volume13
Issue number12
DOIs
Publication statusPublished - 2018

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cystic fibrosis
Microbiota
intestinal microorganisms
Cystic Fibrosis
Digestive system
Sarcosine
Aminobutyrates
Clostridium
Pediatrics
Uracil
Complex networks
Biomarkers
Ecology
Choline
Metabolism
Ecosystems
gamma-Aminobutyric Acid
Ethanol
Dysbiosis
Throughput

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Gut microbiota signatures in cystic fibrosis : Loss of host CFTR function drives the microbiota enterophenotype. / Vernocchi, Pamela; Del Chierico, Federica; Russo, Alessandra; Majo, Fabio; Rossitto, Martina; Valerio, Mariacristina; Casadei, Luca; La Storia, Antonietta; De Filippis, Francesca; Rizzo, Cristiano; Manetti, Cesare; Paci, Paola; Ercolini, Danilo; Marini, Federico; Fiscarelli, Ersilia Vita; Dallapiccola, Bruno; Lucidi, Vincenzina; Miccheli, Alfredo; Putignani, Lorenza.

In: PLoS One, Vol. 13, No. 12, 2018, p. e0208171.

Research output: Contribution to journalArticle

Vernocchi, P, Del Chierico, F, Russo, A, Majo, F, Rossitto, M, Valerio, M, Casadei, L, La Storia, A, De Filippis, F, Rizzo, C, Manetti, C, Paci, P, Ercolini, D, Marini, F, Fiscarelli, EV, Dallapiccola, B, Lucidi, V, Miccheli, A & Putignani, L 2018, 'Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype', PLoS One, vol. 13, no. 12, pp. e0208171. https://doi.org/10.1371/journal.pone.0208171
Vernocchi, Pamela ; Del Chierico, Federica ; Russo, Alessandra ; Majo, Fabio ; Rossitto, Martina ; Valerio, Mariacristina ; Casadei, Luca ; La Storia, Antonietta ; De Filippis, Francesca ; Rizzo, Cristiano ; Manetti, Cesare ; Paci, Paola ; Ercolini, Danilo ; Marini, Federico ; Fiscarelli, Ersilia Vita ; Dallapiccola, Bruno ; Lucidi, Vincenzina ; Miccheli, Alfredo ; Putignani, Lorenza. / Gut microbiota signatures in cystic fibrosis : Loss of host CFTR function drives the microbiota enterophenotype. In: PLoS One. 2018 ; Vol. 13, No. 12. pp. e0208171.
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abstract = "BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.",
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T1 - Gut microbiota signatures in cystic fibrosis

T2 - Loss of host CFTR function drives the microbiota enterophenotype

AU - Vernocchi, Pamela

AU - Del Chierico, Federica

AU - Russo, Alessandra

AU - Majo, Fabio

AU - Rossitto, Martina

AU - Valerio, Mariacristina

AU - Casadei, Luca

AU - La Storia, Antonietta

AU - De Filippis, Francesca

AU - Rizzo, Cristiano

AU - Manetti, Cesare

AU - Paci, Paola

AU - Ercolini, Danilo

AU - Marini, Federico

AU - Fiscarelli, Ersilia Vita

AU - Dallapiccola, Bruno

AU - Lucidi, Vincenzina

AU - Miccheli, Alfredo

AU - Putignani, Lorenza

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.

AB - BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.

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DO - 10.1371/journal.pone.0208171

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JO - PLoS One

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