FFC#19/2017

A longitudinal metagenomic analysis to uncover microbial signatures of CF lung disease: unravelling host-microbial community interactions in humans and animal models

FFC#19/2017

A longitudinal metagenomic analysis to uncover microbial signatures of CF lung disease: unravelling host-microbial community interactions in humans and animal models

PRINCIPAL INVESTIGATOR

Annamaria Bevivino (ENEA, Divisione Biotecnologie e Agroindustria, Lab. Sostenibilità, Qualità e Sicurezza delle Produzioni Agroalimentari, Centro Ricerche Casaccia, Roma)

Partner

Alessio Mengoni (Dip. di Biologia, Università degli Studi di Firenze); Nicola Segata (CIBIO, Laboratorio di Metagenomica computazionale, Università di Trento)

RESEARCHERS

14

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

2 years

GOAL

€ 60.000 €

RESULTS

Twenty-two subjects with CF, with a severe/moderate pulmonary disease, were followed over a 15-month period. Functional and taxonomic features of bacterial airway microbiome of CF patients were inferred from shotgun metagenomic data obtained from sputum samples. Also, male CFTR tm1UNCTgN (FABPCFTR) and their WT congenic mice were studied at seven days post-infection to track changes of the gut and lung microbiome during chronic infection.
The lung microbiome of CF patients showed an extraordinary resilience of the main CF pathogens with patient-specific colonization even at strain-level. Genes associated to metabolic pathways (including antibiotic-resistance genes) were less variable but highly patient-specific suggesting the need for future development of personalized therapeutic approaches based on patient-specific airways microbiome. CFTR-deficient and WT congenic mice do not cluster separately for lung following Pseudomonas aeruginosa chronic infection, while a separation of the gut microbiota with respect to the mutation was found, suggesting that the CFTR genotype has more influence in our animal model for the gut microbiota than for lung microbiota. Animal studies will also assist in the development of microbiome manipulation of lung microbiome aimed to restore “healthy” microbial communities.


Congress abstracts

– Bevivino A, Bacci G, Taccetti G et al. “The personalised temporal dynamics of microbiome in the airways of cystic fibrosis patients” 42nd European Cystic Fibrosis Conference, 5-8 June 2019, Liverpool, UK
– Bevivino A “The airway microbiome in cystic fibrosis: where are we now “Microbiota” MI, Milan, 5-7 November 2018
– Bacci G, Taccetti G, Dolce D et al. “Environmental microbial signatures revealed by metagenomic analysis of the airways of cystic fibrosis patients” XV FISV Congress, Sapienza University Rome, 18-21 September 2018

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models