Applied Microbiology

1. Skin microbiota, probiotics and their supernatants in inflammatory skin diseases and non melanoma skin cancer (NMSC). The correlation between several skin disorders, such as psoriasis/atopic dermatitis (AD) and skin dysbiosis, has been confirmed. Recent research is beginning to demonstrate peculiar imbalances in the skin microbiota even in NMSC. Among microbial species, the contribution of S. aureus, already consolidated for AD and psoriasis, seems to be evident also in this disease. In this context, specific probiotics, such as Lacticaseibacillus rhamnosus,Lactobacillus johnsonii and Bifidobacteria spp., appear to play a protective role. Based on this evidence, the research group is demonstrating the effect of selected live, tyndallized probiotic strains and their supernatants on the bacterial load, viability, virulence and metagenomic sequence of S. aureus, through culturomic, metabolic, biochemical and molecular analysis. Their ability to protect human skin keratinocytes from DNA damage induced by this opportunistic pathogen and to promote the healing of infected wounds is also under study.
2. Oral microbiota, probiotics and vitamin D in chronic inflammatory, autoimmune and tumor oropharyngeal disorders. The human microbiota and vitamin D play a primary role in maintaining health; much of their impact on inflammatory, autoimmune, precancerous, and malignant conditions of the oropharynx is still largely unknown. Mainly human papillomaviruses at high risk of transformation, Fusobacterium nucleatum, Porphyromonas gingivalis, Pseudomonas aeruginosa and Candida spp are highly represented in patients affected by oral Lichen Planus (OLP) and oropharyngeal squamous cell tumors (OPSCC). Aggregatibacter actinomycetemcomitans, Streptococcus mitis, and mutans, also known for their involvement in oropharyngeal disorders, have recently been recognized as leaders in numerous systemic conditions, such as infective endocarditis and neurodegenerative disorders. Regarding vitamin D, often deficient in these patients, despite its documented antimicrobial/antitumor action at the intestinal level, its function in the oropharynx has not yet been evaluated. The Applied Microbiology group is demonstrating the mechanisms through which vitamin D, selected probiotic strains and their supernatants, influence the viability and virulence of oral pathogens implicated in these disorders; their activity is also being analyzed in in vitro cultures and co-cultures, in in vivo clinical studies and in ex vivo models.

3. 3D in vitro models of human epithelial/Langerhans cells to simulate skin disorders with microbial involvement. The incidence of chronic inflammatory epithelial, autoimmune and tumor diseases, often characterized by skin dysbiosis, is a rapidly increasing global problem, with a strong impact on the health and life of patients and also on healthcare costs. Therefore, the need for new in vitro study models, which best imitate the in vivo situation and fully respond to the 3R principles (Replace, Reduce, Refine), is more than urgent.The group has documented experience in developing preclinical predictive systems based on human-derived keratinocytes capable of three-dimensional growth. These models, implemented with Langerhans cells, are co-cultured with live patient-derived skin pathogens, and/or their cell-free supernatants. The use of these complex systems represents an essential tool for understanding epithelial pathologies with microbial involvement and for laying the foundations for the development of personalized treatments based on probiotics.

4. Selection of plant extracts for the prevention and containment of multi-resistant pathogens with epithelial involvement. As reported by the World Health Organization (WHO), infections due to multi-drug-resistant (MDR) germs, causing increased morbidity, morbidity and mortality not only in chronically immunocompromised hospitalized individuals, but also in subjects with different degrees of dysbiosis, are now a global challenge. To aggravate this situation, to date the consumption of antibiotics for human and veterinary use in Italy is the highest in Europe, as reported by the Istituto Superiore della Sanità (ISS).To solve this emergency, the Applied Microbiology group is looking for researching and selecting plant extracts, obtained from the most innovative and efficient fermentation processes of agro-industrial biomass deriving from local supply chains (e.g. vines, hazelnuts, cocoa beans, blueberries, rice ). These extracts are selected for their: i) prebiotic properties; ii) ability to maintain and restore skin eubiosis, acting as agents capable of containing the overgrowth and virulence of various MDR opportunistic pathogens such as S. aureus and P. aeruginosa (both clinical isolates and commercial strains), without exerting any toxicity or side effect towards resident commensal microorganisms and host’s cells.

1. Di Cesare F, Calgaro M, Ghini V, Squarzanti DF, De Prisco A, Visciglia A, Zanetta P, Rolla R, Savoia P, Amoruso A, Azzimonti B, Vitulo N, Tenori L, Luchinat C, Pane M. Exploring the Effects of Probiotic Treatment on Urinary and Serum Metabolic Profiles in Healthy Individuals. J Proteome Res. 2023 Dec 1;22(12):3866-3878. doi: 10.1021/acs.jproteome.3c00548. Epub 2023 Nov 16. PMID: 37970754.
2. Clavenna MG, La Vecchia M, Sculco M, Joseph S, Barberis E, Amede E, Mellai M, Brossa S, Borgonovi G, Occhipinti P, Boldorini R, Robotti E, Azzimonti B, Bona E, Pasolli E, Ferrante D, Manfredi M, Aspesi A, Dianzani I. Distinct Signatures of Tumor-Associated Microbiota and Metabolome in Low-Grade vs. High-Grade Dysplastic Colon Polyps: Inference of Their Role in Tumor Initiation and Progression. Cancers (Basel). 2023 Jun 6;15(12):3065. doi: 10.3390/cancers15123065. PMID: 37370676; PMCID: PMC10296265.
3. Zanetta P, Squarzanti DF, di Coste A, Amoruso A, Pane M, Azzimonti B. Growth Conditions Influence Lactobacillus Cell-Free Supernatant Impact on Viability, Biofilm Formation, and Co-Aggregation of the Oral Periodontopathogens Fusobacterium nucleatum and Porphyromonas gingivalis. Biomedicines. 2023 Mar 11;11(3):859. doi: 10.3390/biomedicines11030859. PMID: 36979838; PMCID: PMC10045872.
4. Azzimonti B, Ballacchino C, Zanetta P, Cucci MA, Monge C, Grattarola M, Dianzani C, Barrera G, Pizzimenti S. Microbiota, Oxidative Stress, and Skin Cancer: An Unexpected Triangle. Antioxidants (Basel). 2023 Feb 21;12(3):546. doi: 10.3390/antiox12030546. PMID: 36978794; PMCID: PMC10045429.
5. Zanetta P, Squarzanti DF, di Coste A, Rolla R, Valletti PA, Garzaro M, Dell'Era V, Amoruso A, Pane M, Azzimonti B. In Vitro Selection of Lactobacillus and Bifidobacterium Probiotic Strains for the Management of Oral Pathobiont Infections Associated to Systemic Diseases. Int J Mol Sci. 2022 Dec 18;23(24):16163. doi: 10.3390/ijms232416163. PMID: 36555802; PMCID: PMC9787750.
6. Squarzanti DF, Zanetta P, Ormelli M, Manfredi M, Barberis E, Vanella VV, Amoruso A, Pane M, Azzimonti B. An animal derivative-free medium enhances Lactobacillus johnsonii LJO02 supernatant selective efficacy against the methicillin (oxacillin)-resistant Staphylococcus aureus virulence through key-metabolites. Sci Rep. 2022 May 23;12(1):8666. doi: 10.1038/s41598-022-12718-z. PMID: 35606510; PMCID: PMC9126979.
7. Zanetta P, Squarzanti DF, Sorrentino R, Rolla R, Aluffi Valletti P, Garzaro M, Dell'Era V, Amoruso A, Azzimonti B. Oral microbiota and vitamin D impact on oropharyngeal squamous cell carcinogenesis: a narrative literature review. Crit Rev Microbiol. 2021 Mar;47(2):224-239. doi: 10.1080/1040841X.2021.1872487. Epub 2021 Jan 21. PMID: 33476522
8. Ghini V, Tenori L, Pane M, Amoruso A, Marroncini G, Squarzanti DF, Azzimonti B, Rolla R, Savoia P, Tarocchi M, Galli A, Luchinat C. Effects of Probiotics Administration on Human Metabolic Phenotype. Metabolites. 2020 Oct 7;10(10):396. doi: 10.3390/metabo10100396. PMID: 33036487; PMCID: PMC7601401.
9. Squarzanti DF, Zavattaro E, Pizzimenti S, Amoruso A, Savoia P, Azzimonti B. Non-Melanoma Skin Cancer: news from microbiota research. Crit Rev Microbiol. 2020 Aug;46(4):433-449. doi: 10.1080/1040841X.2020.1794792. Epub 2020 Jul 21. PMID: 32692305
10. Squarzanti DF, Sorrentino R, Landini MM, Chiesa A, Pinato S, Rocchio F, Mattii M, Penengo L, Azzimonti B. Human papillomavirus type 16 E6 and E7 oncoproteins interact with the nuclear p53-binding protein 1 in an in vitro reconstructed 3D epithelium: new insights for the virus-induced DNA damage response. Virol J. 2018 Nov 16;15(1):176. doi: 10.1186/s12985-018-1086-4. PMID: 30445982; PMCID: PMC6240266.

1. Georg Alexander Häcker: (Institute for Microbiology and Hygiene, Freiburg, Germany
   georg.haecker@uniklinik-freiburg.de; www.uniklinik-freiburg.de/mikrobiologie)
2. Moreno Lelli: Centro di Risonanza magnetica, Dipartimento di Chimica, Università di Firenze; moreno.lelli@unifi.it; https://www.cerm.unifi.it/about-us/people/moreno-lelli)
3. Claudio Luchinat: Centro di Risonanza magnetica, Dipartimento di Chimica, Università di Firenze; luchinat@cerm.unifi.it; www.cerm.unifi.it/about-us/people/claudio-luchinat)
4. Leonardo Tenori: Centro di Risonanza magnetica, Dipartimento di Chimica, Università di Firenze; tenori@unifi.it; https://www.cerm.unifi.it/about-us/people/leonardo-tenori)
5. Stefania Pizzimenti: Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino; stefania.pizzimenti@unito.it; www.unito.it/persone/spizzime)
6. Nicola Vitulo Dipartimento di Biotecnologie, Università di Verona; nicola.vitulo@univr.it; https://www.dbt.univr.it/?ent=persona&id=13118
7. Matteo Calgaro Dipartimento di Biotecnologie, Università di Verona; matteo.calgaro_01@univr.it; https://www.dbt.univr.it/?ent=persona&id=50712;
8. Probiotical research Srl: https://www.probiotical.com/index.php?lingua=it
9. Roelmi HPC: https://www.roelmihpc.com/
10. UPO (alphabetical order)

            Anna Aspesi anna.aspesi@med.uniupo.it

Elettra Barberis elettra.barberis@uniupo.it

Irma Dianzani irma.dianzani@med.uniupo.it

Massimiliano Garzaro massimo.garzaro@med.uniupo.it

Marcello Manfredi marcello.manfredi@med.uniupo.it

Mario Migliario mario.migliario@med.uniupo.it

Roberta Rolla roberta.rolla@med.uniupo.it

Paola Savoia paola.savoia@med.uniupo.it

Paolo Aluffi Valletti paolo.aluffi@med.uniupo.it

Elisa Zavattaro elisa.zavattaro@med.uniupo.it

1. Since2023: Bando Prin 2022 PNRR”. “Dissecting the role of Staphylococcus aureus in anti-IL-4/IL-13 and anti-JAK-treated atopic dermatitis patients”. Ruolo: Membro Collaboratore Unità di Ricerca UPO (PI. Prof. Paola Savoia) e Co-Responsabile scientifico: analisi microbiologiche e allestimento/caratterizzazione modelli 3D di co-culture eucarioti-procarioti.
2. Since 2023: “Roelmi HPC”. “Selezione di estratti vegetali per la prevenzione e il contenimento di patogeni multi-resistenti a interessamento epiteliale”. Ruolo: PI
3. Since 2020: "PROBIOTICAL RESEARCH SRL". “Impatto di probiotici selezionati e della vitamina D sulla tumorigenesi del distretto testa collo: un approccio integrato ". Ruolo: PI
4. Since 2019: "PROBIOTICAL RESEARCH SRL". "Caratterizzazione del microbiota, microbioma e metaboloma di pazienti immunocompormessi affetti da tumori cutanei non associati al melanoma”. Ruolo: PI
5. 2019-2022: "FAR 2017” FONDI DI RICERCA DI ATENEO" (UPO). "Contributo del microbiota orale e della vitamina D nello sviluppo di patologie cardiovascolari in pazienti con tumori del distretto testa collo”. Risoluzioni 3.4 e 6.4.1 Dipartimento di scienze dalla salute (UPO) 04-06-2019. Ruolo: PI
6. 2021: AIRC Investigator grant”. “Dissecting the interaction among the intestinal microbiota, obesity and colon cancer development (DiaMOnD). Ruolo: Collaboratore
7. 2020: “FASTMED ITALIA SRL”. "Valutazione dell’attività biocida di COMVIR, tessuto non tessuto per uso medico". Ruolo: PI

Barbara Azzimonti, Group leader

Paola Zanetta, PhD student “Food, health and Longevity”, XXXVI cycle

Marta Armari, PhD student “Food, health and Longevity studies”, XXXIX cycle

Alice Galeazzi, medical Biotec student

Alessia Grossetti, medical Biotec student