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1. BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

Author

Abbass Darwich, Chiara Pozzi, Giulia Fornasa, Michela Lizier, Elena Azzolini, Ilaria Spadoni, Francesco Carli, Antonio Voza, Antonio Desai, Carlo Ferrero, Luca Germagnoli, ICH COVID‐19 Task‐force, Alberto Mantovani, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Ana Lleo De Nalda, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, Farina Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Ana Rita Gomes, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
BNT162b2, IgA, IgG, mucosal immunity, SARS‐CoV‐2, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

Published
2022
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2. A ‘Multiomic’ Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
Metabolome, Microbiota, CHI3L1, COVID-19, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2022
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3. Microbial composition associated with biliary stents in patients undergoing pancreatic resection for cancer

Author

Blanco-Míguez, Aitor, Carloni, Sara, Cardenas, Cindy, Dioguardi, Carola Conca, Lambroia, Luca, Capretti, Giovanni, Nappo, Gennaro, Fugazza, Alessandro, Capogreco, Antonio, Armanini, Federica, Asnicar, Francesco, Dubois, Leonard, Golzato, Davide, Manghi, Paolo, Pinto, Federica, Scuderi, Cristina, Casari, Erminia, Montorsi, Marco, Anderloni, Andrea, Rescigno, Maria, Repici, Alessandro, Zerbi, Alessandro, Peano, Clelia, Tamburini, Sabrina, Rusconi, Roberto, and Segata, Nicola

Published
2024
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4. The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19

Author

Accornero, Stefano, Aghemo, Alessio, Ali, Hussam, Angelini, Claudio, Arcari, Ivan, Arosio, Paola, Azzolini, Elena, Baccarin, Alessandra, Badalamenti, Salvatore, Baggio, Sara, Barbagallo, Michela, Barberi, Caterina, Barbic, Franca, Barbieri, Viviana, Barbone, Alessandro, Basciu, Alessio, Bocciolone, Monica, Borea, Federica, Borroni, Mario, Bresciani, Gianluigi, Brunetta, Enrico, Bulletti, Cinzia, Cadonati, Cristina, Calabro', Lorenzo, Calatroni, Marta, Calvetta Albania, Antonietta, Cannata, Francesco, Canziani, Lorenzo, Capretti Giovanni, Luigi, Carlani, Elisa, Carrone, Flaminia, Casana, Maddalena, Cecconi, Maurizio, Ceriotti, Carlo, Ciccarelli, Michele, Cimino, Matteo, Ciuffini, Leonardo, Colaizzi, Chiara, Colapietro, Francesca, Costa, Guido, Cozzi, Ottavia, Craviotto, Vincenzo, Crespi, Chiara, Crippa, Massimo, Da Rio, Leonardo, Dal Farra, Sara, D'Antonio, Federica, De Ambroggi, Guido, De Donato, Massimo, De Lucia, Francesca, De Santis, Maria, Delle Rose, Giacomo, Di Pilla, Marina, Dipaola, Franca, Dipasquale, Andrea, Dipasquale, Angelo, Droandi, Ginevra, Fazio, Roberta, Ferrante, Giuseppe, Ferrara Elisa, Chiara, Ferrari Matteo, Carlo, Ferri, Sebastian, Folci, Marco, Foresti, Sara, Franchi, Eloisa, Fraolini, Elia, Fugazza, Alessandro, Furfaro, Federica, Galimberti, Paola, Galtieri Alessia, Piera, Gavazzi, Francesca, Generali, Elena, Goletti, Benedetta, Guidelli, Giacomo, Jacobs, Flavia, Kurihara, Hayato, Lagioia, Michele, Libre', Luca, Lleo, Ana, Loiacono, Ferdinando, Lughezzani, Giovanni, Maccallini, Marta, Maiorino Alfonso, Francesco, Malesci, Alberto, Mantovani, Riccardo, Marchettini, Davide, Marinello, Arianna, Markopoulos, Nikolaos, Masetti, Chiara, Milani, Angelo, Mirani, Marco, Morelli, Paola, Motta, Francesca, Mundula, Valeria, Nigro, Mattia, Omodei, Paolo, Ormas, Monica, Pagliaro, Arianna, Paliotti, Roberta, Parigi Tommaso, Lorenzo, Pedale, Rosa, Pegoraro, Francesco, Pellegatta, Gaia, Pellegrino, Marta, Petriello, Gennaro, Piccini, Sara, Pocaterra, Daria, Poliani, Laura, Preatoni, Paoletta, Procopio, Fabio, Puggioni, Francesca, Pugliese, Luca, Racca, Francesca, Randazzo, Michele, Regazzoli Lancini, Damiano, Reggiani, Francesco, Rodolfi, Stefano, Ruongo, Lidia, Sacco, Clara, Sandri Maria, Teresa, Savi, Marzia, Scarfo', Iside, Shiffer, Dana, Sicoli, Federico, Solano, Simone, Solitano, Virginia, Stainer, Anna, Stella Matteo, Carlo, Strangio, Giuseppe, Taormina, Antonio, Testoni, Lucia, Tordato, Federica, Trabucco, Angela, Ulian, Luisa, Valentino, Rossella, Valeriano, Chiara, Vena, Walter, Verlingieri, Simona, Vespa, Edoardo, Voza, Antonio, Zanuso, Valentina, Zilli, Alessandra, Anfray, Clement, Belgiovine, Cristina, Bertocchi, Alice, Bombace, Sara, Brescia, Paola, Calcaterra, Francesca, Calvi, Michela, Cancellara, Assunta, Capucetti, Arianna, Carenza, Claudia, Carloni, Sara, Carnevale, Silvia, Cazzetta, Valentina, Coianiz, Nicolò, Darwich, Abbass, Davoudian, Sadaf, De Paoli, Federica, Di Donato, Rachele, Digifico, Elisabeth, Durante, Barbara, Farina Floriana, Maria, Ferrari, Valentina, Fornasa, Giulia, Franzese, Sara, Ghasemi, Somayehsadat, Gil Gomez, Antonio, Giugliano, Silvia, Gomes Ana, Rita, Lizier, Michela, Lo Cascio, Antonino, Melacarne, Alessia, Mozzarelli, Alessandro, My, Ilaria, Oresta, Bianca, Pasqualini, Fabio, Pastò, Anna, Pelamatti, Erica, Perucchini, Chiara, Pozzi, Chiara, Rimoldi, Valeria, Rimoldi, Monica, Scarpa, Alice, Scavello, Francesco, Silvestri, Alessandra, Sironi, Marina, Spadoni, Ilaria, Spano', Salvatore, Spata, Gianmarco, Supino, Domenico, Tentorio, Paolo, Ummarino, Aldo, Valentino, Sonia, Zaghi, Elisa, Zanon, Veronica, Mapelli, Sarah N., Nappi, Emanuele, García Martín, Ian David, Leone, Roberto, Angelotti, Giovanni, Zhong, Hang, Magrini, Elena, Stravalaci, Matteo, Protti, Alessandro, Santini, Alessandro, Costantini, Elena, Savevski, Victor, Bottazzi, Barbara, Bartoletti, Michele, Mantovani, Alberto, and Garlanda, Cecilia

Published
2024
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5. Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila

Author

Silvestri, Alessandra, Gil-Gomez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gomez, Manuel, Penna, Giuseppe, Sannino, Alessandro, and Rescigno, Maria

Published
2023
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9. Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth

Author

Zagato, Elena, Pozzi, Chiara, Bertocchi, Alice, Schioppa, Tiziana, Saccheri, Fabiana, Guglietta, Silvia, Fosso, Bruno, Melocchi, Laura, Nizzoli, Giulia, Troisi, Jacopo, Marzano, Marinella, Oresta, Bianca, Spadoni, Ilaria, Atarashi, Koji, Carloni, Sara, Arioli, Stefania, Fornasa, Giulia, Asnicar, Francesco, Segata, Nicola, Guglielmetti, Simone, Honda, Kenya, Pesole, Graziano, Vermi, William, Penna, Giuseppe, and Rescigno, Maria

Published
2020
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10. Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization.

Author

Mangioni, Davide, Fox, Valeria, Saltini, Paola, Lombardi, Andrea, Bussini, Linda, Carella, Francesco, Cariani, Lisa, Comelli, Agnese, Matinato, Caterina, Muscatello, Antonio, Teri, Antonio, Terranova, Leonardo, Cento, Valeria, Carloni, Sara, Bartoletti, Michele, Alteri, Claudia, and Bandera, Alessandra

Subjects
STREPTOCOCCAL diseases, WHOLE genome sequencing, SINGLE nucleotide polymorphisms, CHILD patients, SYMPTOMS
Abstract

Background: Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally. Methods: GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity. Results: Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p < 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045). Conclusions: This study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance. [ABSTRACT FROM AUTHOR]

Published
2024
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11. MSIpixel: a fully automated pipeline for compound annotation and quantitation in mass spectrometry imaging experiments.

Author

Morosi, Lavinia, Miotto, Matteo, Timo, Sara, Carloni, Sara, Bruno, Eleonora, Meroni, Marina, Menna, Elisabetta, Lodato, Simona, Rescigno, Maria, and Martano, Giuseppe

Subjects
ANNOTATIONS, COMPLEX matrices, SINGLE molecules, SMALL molecules, METABOLOMICS
Abstract

Mass spectrometry imaging (MSI) is commonly used to map the spatial distribution of small molecules within complex biological matrices. One of the major challenges in imaging MS-based spatial metabolomics is molecular identification and metabolite annotation, to address this limitation, annotation is often complemented with parallel bulk LC-MS2-based metabolomics to confirm and validate identifications. Here we applied MSI method, utilizing data-dependent acquisition, to visualize and identify unknown molecules in a single instrument run. To reach this aim we developed MSIpixel, a fully automated pipeline for compound annotation and quantitation in MSI experiments. It overcomes challenges in molecular identification, and improving reliability and comprehensiveness in MSI-based spatial metabolomics. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila

Author

Gelesis, Junta de Andalucía, Silvestri, Alessandra, Gil-Gómez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gómez, Manuel, Penna, Giuseppe, Sannino, Alessandro, Rescigno, Maria, Gelesis, Junta de Andalucía, Silvestri, Alessandra, Gil-Gómez, Antonio, Vitale, Milena, Braga, Daniele, Demitri, Christian, Brescia, Paola, Madaghiele, Marta, Spadoni, Ilaria, Jones, Bryan, Fornasa, Giulia, Mouries, Juliette, Carloni, Sara, Lizier, Michela, Romero-Gómez, Manuel, Penna, Giuseppe, Sannino, Alessandro, and Rescigno, Maria

Abstract

The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton. It protects from gut barrier permeability disruption and induces rapid and consistent changes in the gut microbiota composition, specifically fostering Akkermansia muciniphila expansion. The mechanobiological, physical, and chemical structures of the gel are required for A. muciniphila growth. OSH treatment induces weight loss and reduces fat accumulation, in both preventative and therapeutic settings. OSH usage also prevents liver steatosis, immune infiltration, and fibrosis, limiting the progression of non-alcoholic fatty liver disease. Our work shows the potential of using OSH as a non-systemic mechanobiological approach to treat metabolic syndrome and its comorbidities.

Published
2023

13. Role of the Maternal Gut Microbiota in Immune Activation at the Maternal-Fetal Interface: Impact on Preeclampsia

Author

Giugliano, Silvia, Carloni, Sara, Schorn, Tilo, and Rescigno, Maria

Subjects
Preeclampsia, reproductive immunology, gut microbiota, carbohydrate metabolism, metabolic biomarker
Abstract

Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5-8% of gestations worldwide. Several factors such as abnormalities in maternal immunity, metabolic disorders and gut dysbiosis are known to contribute to disease development. Here, we show that dysbiosis in pregnant C57BL/6J dams increased fetal resorption, impaired placental development and altered vascularization. These changes positively correlated with increased hypoxia and reduced uterine NK cell number. Moreover, intestinal dysbiosis significantly perturbated placental carbohydrate metabolism impacting NK cell IFN-γ secretion. Of note, glucose supplementation restored placental NK cell functionin vitro,suggesting that the impairment was reversible and dependent on a lower glycolytic rate. In this work,maternal gut microbiota emerges as a key player in carbohydrate metabolism during pregnancy with a pivotal role in controlling placental immunity and pregnancy outcome.These results provide insights for the identification of metabolic biomarkers and propose the microbiota as apotentially amenable target for preventive interventionof preeclampsia.&nbsp

Published
2023
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15. Abstract 3059: Microbiota mediated CHI3L1 expression as a novel candidate biomarker for breast cancer progression

Author

Mozzarelli, Alessandro Mauro, primary, Carloni, Sara, additional, Ferrrari, Valentina, additional, Giugliano, Silvia, additional, Tiraboschi, Luca, additional, Cascio, Antonino Lo, additional, Fornasa, Giulia, additional, Braga, Daniele, additional, Golzato, Davide, additional, Segata, Nicola, additional, Penna, Giuseppe, additional, and Rescigno, Maria, additional

Published
2022
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17. A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
PCA, principal component analysis, SVM, support vector machine, ESI, electrospray ionization, FDR, false discovery rate, Microbiota, IgG, immunoglobulin G, COVID-19, LR, logistic regression, Original Research—Basic, CHI3L1, chitinase 3-like-1, ELISA, enzyme-linked immunosorbent assay, PTX3, pentraxin 3, CI, confidence interval, AUC, area under the curve, RFE, recursive feature elimination, Metabolome, CHI3L1, COVID-19, coronavirus disease 19, DT, decision tree
Abstract

Background and Aims The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2021

18. Identification of a choroid plexus vascular barrier closing during intestinal inflammation

Author

Carloni, Sara, primary, Bertocchi, Alice, additional, Mancinelli, Sara, additional, Bellini, Martina, additional, Erreni, Marco, additional, Borreca, Antonella, additional, Braga, Daniele, additional, Giugliano, Silvia, additional, Mozzarelli, Alessandro M., additional, Manganaro, Daria, additional, Fernandez Perez, Daniel, additional, Colombo, Federico, additional, Di Sabatino, Antonio, additional, Pasini, Diego, additional, Penna, Giuseppe, additional, Matteoli, Michela, additional, Lodato, Simona, additional, and Rescigno, Maria, additional

Published
2021
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20. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

Author

Bertocchi, Alice, primary, Carloni, Sara, additional, Ravenda, Paola Simona, additional, Bertalot, Giovanni, additional, Spadoni, Ilaria, additional, Lo Cascio, Antonino, additional, Gandini, Sara, additional, Lizier, Michela, additional, Braga, Daniele, additional, Asnicar, Francesco, additional, Segata, Nicola, additional, Klaver, Chris, additional, Brescia, Paola, additional, Rossi, Elio, additional, Anselmo, Achille, additional, Guglietta, Silvia, additional, Maroli, Annalisa, additional, Spaggiari, Paola, additional, Tarazona, Noelia, additional, Cervantes, Andres, additional, Marsoni, Silvia, additional, Lazzari, Luca, additional, Jodice, Maria Giovanna, additional, Luise, Chiara, additional, Erreni, Marco, additional, Pece, Salvatore, additional, Di Fiore, Pier Paolo, additional, Viale, Giuseppe, additional, Spinelli, Antonino, additional, Pozzi, Chiara, additional, Penna, Giuseppe, additional, and Rescigno, Maria, additional

Published
2021
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23. STUDIO DELLA FUNZIONE E DEL PROFILO DEI MICRORNA IN MICROPARTICELLE CIRCOLANTI ISOLATE DA PAZIENTI ‘TRIPLI NEGATIVI’ E JAK2V617F MUTATI CON MIELOFIBROSI

Author

Dorian Forte, DARIA SOLLAZZO, MARTINA BARONE, CRISTINA MORSIANI, Ricci, F., Carloni, Sara, Fabbri, F., Auteri, G., Romano, M., Ottaviani, M., Tazzari, P. L., MICHELE CAVO, GIOVANNI MARTINELLI, Claudio Franceschi, Vianelli, N., Miriam Capri, FRANCESCA PALANDRI, Lucia Catani, and D. Forte, D. Sollazzo, M. Barone, C. Morsiani, F. Ricci, S. Carloni, F. Fabbri, G. Auteri, M. Romano, M. Ottaviani, P.L. Tazzari, M. Cavo, G. Martinelli, C. Franceschi, N. Vianelli, M. Capri, F. Palandri, L. Catani

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, nutritional and metabolic diseases, circulating microparticles, triple negative, JAK2V617F, Myelofibrosis, apoptosis, microRNA, skin and connective tissue diseases
Abstract

Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by clonal hemopoiesis, inflammatory microenvironment and mutations in JAK2, MPL, or CALR genes. Around 10% of patients (pts) do not carry the 3 mutations (Triple negative (TN)). Microparticles (MPs; 0.1-1 μm) are small vesicles deriving from plasma membrane during homeostasis and cell activation of a wide variety of cells with a role in intercellular signalling. Circulating MPs are increased in inflammation and cancer including MPN. However, their role in the pathogenesis of MF is still elusive. Here we compared phenotype, function and microRNAs (miRs) expression of isolated MPs of JAK2V617F mutated and TN pts. Methods: Peripheral blood was collected from 10 MF pts (at diagnosis or out of cytotoxic treatment for at least 3 months) and 10 age/sex-matched healthy donors (HD). MF pts were JAK2V617F mutated (n=5) and TN n=5). MPs were purified from 2 mL of platelet poor plasma by ultracentrifugation and quantified using Nanosight technology. Isolated MPs were characterized by flow cytometry (CytoFLEX, Beckman Coulter) for the expression of platelets (PLT:CD61+CD62P+) and megakaryocytes (MK:CD61+CD62P-) markers. MPs were then analyzed for their ability to modulate the in vitro viability of immunomagnetically isolated CD34+ cells from MF pts and cord blood (CB). MiRs expression of isolated MPs (10e9) from 3 JAK2V617F mutated, 3 TN pts and 3 HD was investigated using TaqMan™ Array Human MicroRNA A Cards (ThermoFisher). Results: The mean number of plasma MPs isolated from MF pts was similar to HD (5*10e10/mL). However, flow cytometry analysis revealed that the mean percentage of PLT-MPs was significantly increased (p

Published
2018

24. SMALL RNAS AND REGULATION OF VIRULENCE TRAITS IN PSEUDOMONAS AERUGINOSA

Author

CARLONI, SARA

Abstract

This PhD project aimed at the functional characterization of novel Pseudomonas aeruginosa small RNAs (sRNAs) involved in virulence-associated regulatory networks. Following an initial phase of screenings for sRNA candidates involved in the regulation of virulence traits, the work focused on the sRNAs SPA0122 and SPA0084. SPA0122, renamed ErsA, is transcribed from the same genomic context of the well-known Escherichia coli Spot 42. We show that, different from Spot 42, ErsA is under the transcriptional control of the envelope stress response, which is known to impact the pathogenesis of P. aeruginosa through the activity of the alternative sigma factor ?22. The transcriptional responsiveness of ErsA RNA also spans infection-relevant cues that P. aeruginosa can experience in mammalian hosts, such as limited iron availability, temperature shifts from environmental to body temperature and reduced oxygen conditions. Another difference between Spot 42 and ErsA is that ErsA does not seem to be involved in the regulation of carbon source catabolism. Instead, our results suggest that ErsA is linked to anabolic functions for the synthesis of exoproducts from sugar precursors. We show that ErsA directly operates in the negative post-transcriptional regulation of the algC gene that encodes the virulence-associated enzyme AlgC, which provides sugar precursors for the synthesis of several P. aeruginosa polysaccharides. Like ErsA, the activation of algC expression is also dependent on ?22. Altogether, our results suggest that ErsA and ?22 combine in an incoherent feed-forward loop to fine-tune AlgC enzyme expression. As regards SPA0084, our results indicate that is embedded in the P. aeruginosa quorum sensing (QS) with the role of wiring las to pqs systems. In fact, we show that SPA0084 responds to the las regulator LasR and impacts positively the synthesis of the pqs quinolone signal PQS. Our results suggest that the stimulation of PQS synthesis is mediated by a positive post-transcriptional effect of SPA0084 on the pqsC gene belonging to the pqsABCD cluster involved in the biosynthesis of the PQS-precursor HHQ. We suggest that a fine balancing between the different already known regulatory effects of LasR on PQS synthesis and this one mediated by SPA0084 can influence timing and magnitude of expression of QS-regulated virulence factors. This view is consistent with the evidence that perturbations of SPA0084 levels affect pyocyanin synthesis, biofilm formation and swarming motility, processes that are known to be influenced by PQS synthesis. Besides being regulated by LasR, SPA0084 responds to infection relevant cues that P. aeruginosa can experience in mammalian hosts such as temperature and oxygen availability. Furthermore, SPA0084 shows a growth phasedependent pattern of expression, being up-regulated in stationary phase. Sequence analysis of the spa0084 promoter region strongly suggests that the growth phase-dependent pattern of SPA0084 expression is due to the activity of the alternative ? factor RpoS whose significance as global factor controlling quorum sensing gene expression was shown previously. Together, these SPA0084 regulations are expected to contribute to the fine co-modulation of PQS synthesis.

Published
2015
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27. Post-transcriptional regulation of the virulence-associated enzyme Alg C by the σ22-dependent small RNA Ers A of P seudomonas aeruginosa.

Author

Ferrara, Silvia, Carloni, Sara, Fulco, Roberta, Falcone, Marilena, Macchi, Raffaella, and Bertoni, Giovanni

Subjects
*GENETIC transcription in bacteria, *VIRULENCE of bacteria, *NON-coding RNA, *BACTERIAL enzymes, *SIGMA factor (Transcription factor), *PSEUDOMONAS aeruginosa
Abstract

The small RNA Ers A of P seudomonas aeruginosa, transcribed from the same genomic context of the well-known E scherichia coli Spot 42, has been characterized. We show that, different from Spot 42, Ers A is under the transcriptional control of the envelope stress response, which is known to impact the pathogenesis of P . aeruginosa through the activity of the alternative sigma factor σ22. The transcriptional responsiveness of Ers A RNA also spans infection-relevant cues that P . aeruginosa can experience in mammalian hosts, such as limited iron availability, temperature shifts from environmental to body temperature and reduced oxygen conditions. Another difference between Spot 42 and Ers A is that Ers A does not seem to be involved in the regulation of carbon source catabolism. Instead, our results suggest that Ers A is linked to anabolic functions for the synthesis of exoproducts from sugar precursors. We show that Ers A directly operates in the negative post-transcriptional regulation of the alg C gene that encodes the virulence-associated enzyme Alg C, which provides sugar precursors for the synthesis of several P . aeruginosa polysaccharides. Like Ers A, the activation of alg C expression is also dependent on σ22. Altogether, our results suggest that Ers A and σ22 combine in an incoherent feed-forward loop to fine-tune Alg C enzyme expression. [ABSTRACT FROM AUTHOR]

Published
2015
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29. MSIpixel: a fully automated pipeline for compound annotation and quantitation in mass spectrometry imaging experiments.

Author

Morosi L, Miotto M, Timo S, Carloni S, Bruno E, Meroni M, Menna E, Lodato S, Rescigno M, and Martano G

Subjects
Reproducibility of Results, Mass Spectrometry, Metabolomics methods
Abstract

Mass spectrometry imaging (MSI) is commonly used to map the spatial distribution of small molecules within complex biological matrices. One of the major challenges in imaging MS-based spatial metabolomics is molecular identification and metabolite annotation, to address this limitation, annotation is often complemented with parallel bulk LC-MS2-based metabolomics to confirm and validate identifications. Here we applied MSI method, utilizing data-dependent acquisition, to visualize and identify unknown molecules in a single instrument run. To reach this aim we developed MSIpixel, a fully automated pipeline for compound annotation and quantitation in MSI experiments. It overcomes challenges in molecular identification, and improving reliability and comprehensiveness in MSI-based spatial metabolomics., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2023
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