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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.

Details

Title
Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma
Author
Vandoni, Giulia 1 ; Federica D’Amico 2   VIAFID ORCID Logo  ; Fabbrini, Marco 2   VIAFID ORCID Logo  ; Mariani, Luigi 3   VIAFID ORCID Logo  ; Sieri, Sabina 4   VIAFID ORCID Logo  ; Casirati, Amanda 5   VIAFID ORCID Logo  ; Lorenza Di Guardo 6 ; Michele Del Vecchio 6 ; Anichini, Andrea 7   VIAFID ORCID Logo  ; Mortarini, Roberta 7 ; Sgambelluri, Francesco 7 ; Celano, Giuseppe 8   VIAFID ORCID Logo  ; Serale, Nadia 8   VIAFID ORCID Logo  ; De Angelis, Maria 8   VIAFID ORCID Logo  ; Brigidi, Patrizia 9 ; Gavazzi, Cecilia 1 ; Turroni, Silvia 10   VIAFID ORCID Logo 

 Clinical Nutrition Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 
 Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy 
 Data Science Unit, Fondazione IRCCS Istituito Nazionale dei Tumori, 20133 Milan, Italy 
 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 
 Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy 
 Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 
 Human Tumors Immunobiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy[email protected] (R.M.); 
 Department of Soil, Plant and Food Science (DiSSPA), University of Bari Aldo Moro, 70126 Bari, Italy 
 Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy 
10  Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy 
First page
11611
Publication year
2023
Publication date
2023
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2843071822
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.