My PhD thesis focused on the correlations between environmental and human microbiomes and their relation with health or disease conditions. In particular, at the environmental level, the hospital environment was analyzed, as it is a reservoir of pathogens responsible for the onset of healthcare-associated infections (HAI), thus its monitoring could be crucial to optimize HAI prevention strategies. To this aim, molecular methods were used in comparison with conventional microbiological methods, showing that NGS, due to its high sensitivity, could be a useful tool for microbial environmental monitoring, especially if flanked by PCR methods for species identification and resistome characterization (Comar et al., 2019). Next, the data obtained from NGS characterization of the microbiome in a pediatric hospital were used to assess the potential of environmental pathogens to colonize the nasal cavities of preterm newborns in a Neonatal Intensive Care Unit (NICU), since the risk for contracting HAI is particularly high in preterm infants. The results, obtained by NGS and qPCR microarray, showed increasing amount of HAI-associated environmental pathogens in the newborn nose with increased stay time in the NICU, highlighting the role of the hospital microbiome in pathogen transmission (Cason et al., 2021). Last, we tested the microbiome variations associated with the use of a probiotic cleaning hygiene system (PCHS) in the Emergency ward of a pediatric hospital during the COVID-19 pandemics, showing that PCHS use was associated with a stable decrease of pathogens (>80% compared to chemical disinfection), and an up to 2-Log decrease of antibiotic resistance genes (ARG) in the microbial population. Notably, despite the presence of SARS-CoV-2 infected patients, the virus was never detected during the PCHS use, supporting the PCHS antiviral activity previously reported in vitro, and suggesting that PCHS may effectively control both the spread of resistant HAI-associated pathogens and of SARS-CoV-2 (Soffritti et al., 2022). On the human microbiome side, we focused on the study of oral and vaginal niches, to clarify whether specific microbiome compositions may be related to increased risk to develop specific virus-induced diseases. First, a comprehensive characterization of the healthy human oral microbiome (HOM) was obtained by WGS, showing the presence of a recognizable core healthy HOM, including bacteria, fungi and viruses. Furthermore, HOM ARG analysis highlighted the presence of several resistances to antibiotics, including macrolide, lincosamides, streptogramin and tetracycline (Caselli, Fabbri, et al., 2020). Since SARS-CoV-2 virus enters the body through the oropharynx, we next investigated the role of HOM in favoring/counteracting the virus replication at the site of entry, showing that HOM dysbiosis correlated with inflammation, COVID-19 severity, and poor with mucosal sIgA response, thus suggesting that HOM could be an important factor in determining the individual susceptibility to SARS-CoV-2 infection and the early virus control (Soffritti et al., 2021). Last, we studied the role of vaginal microbiome in determining the persistence/clearance of HPV infection in CIN2/CIN3 patients undergoing lesion surgical excision. The results showed that dysbiotic microbiomes and inflammation were observed before excision, correlating with the neoplastic disease severity, whereas a decrease of microbiome dysbiosis and pro-inflammatory cytokines were observed in HPV-cleared patients, compared to HPV-recurrent ones (Caselli, D’Accolti, et al., 2020). Overall, the data collected during my PhD support the existence of a deep interconnection between the environmental and human microbiome, and a significant role of the human microbiome in maintaining the health or favoring disease onset.

Investigating the role of environmental and human microbiome in health and disease: focus on pathogen’s monitoring and control

SOFFRITTI, IRENE
2022

Abstract

My PhD thesis focused on the correlations between environmental and human microbiomes and their relation with health or disease conditions. In particular, at the environmental level, the hospital environment was analyzed, as it is a reservoir of pathogens responsible for the onset of healthcare-associated infections (HAI), thus its monitoring could be crucial to optimize HAI prevention strategies. To this aim, molecular methods were used in comparison with conventional microbiological methods, showing that NGS, due to its high sensitivity, could be a useful tool for microbial environmental monitoring, especially if flanked by PCR methods for species identification and resistome characterization (Comar et al., 2019). Next, the data obtained from NGS characterization of the microbiome in a pediatric hospital were used to assess the potential of environmental pathogens to colonize the nasal cavities of preterm newborns in a Neonatal Intensive Care Unit (NICU), since the risk for contracting HAI is particularly high in preterm infants. The results, obtained by NGS and qPCR microarray, showed increasing amount of HAI-associated environmental pathogens in the newborn nose with increased stay time in the NICU, highlighting the role of the hospital microbiome in pathogen transmission (Cason et al., 2021). Last, we tested the microbiome variations associated with the use of a probiotic cleaning hygiene system (PCHS) in the Emergency ward of a pediatric hospital during the COVID-19 pandemics, showing that PCHS use was associated with a stable decrease of pathogens (>80% compared to chemical disinfection), and an up to 2-Log decrease of antibiotic resistance genes (ARG) in the microbial population. Notably, despite the presence of SARS-CoV-2 infected patients, the virus was never detected during the PCHS use, supporting the PCHS antiviral activity previously reported in vitro, and suggesting that PCHS may effectively control both the spread of resistant HAI-associated pathogens and of SARS-CoV-2 (Soffritti et al., 2022). On the human microbiome side, we focused on the study of oral and vaginal niches, to clarify whether specific microbiome compositions may be related to increased risk to develop specific virus-induced diseases. First, a comprehensive characterization of the healthy human oral microbiome (HOM) was obtained by WGS, showing the presence of a recognizable core healthy HOM, including bacteria, fungi and viruses. Furthermore, HOM ARG analysis highlighted the presence of several resistances to antibiotics, including macrolide, lincosamides, streptogramin and tetracycline (Caselli, Fabbri, et al., 2020). Since SARS-CoV-2 virus enters the body through the oropharynx, we next investigated the role of HOM in favoring/counteracting the virus replication at the site of entry, showing that HOM dysbiosis correlated with inflammation, COVID-19 severity, and poor with mucosal sIgA response, thus suggesting that HOM could be an important factor in determining the individual susceptibility to SARS-CoV-2 infection and the early virus control (Soffritti et al., 2021). Last, we studied the role of vaginal microbiome in determining the persistence/clearance of HPV infection in CIN2/CIN3 patients undergoing lesion surgical excision. The results showed that dysbiotic microbiomes and inflammation were observed before excision, correlating with the neoplastic disease severity, whereas a decrease of microbiome dysbiosis and pro-inflammatory cytokines were observed in HPV-cleared patients, compared to HPV-recurrent ones (Caselli, D’Accolti, et al., 2020). Overall, the data collected during my PhD support the existence of a deep interconnection between the environmental and human microbiome, and a significant role of the human microbiome in maintaining the health or favoring disease onset.
CASELLI, Elisabetta
DI VIRGILIO, Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2484935
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