Gut microbiota in very early systemic sclerosis: the first case-control taxonomic and functional characterisation highlighting an altered butyric acid profile
Marco Matucci-Cerinic,
Cosimo Bruni,
Gemma Lepri,
Martina Orlandi,
Serena Guiducci,
Mirko Manetti,
Eloisa Romano,
Irene Rosa,
Silvia Bellando-Randone,
Bianca Saveria Fioretto,
Khadija El Aoufy,
Edda Russo,
Leandro Di Gloria,
Simone Baldi,
Giulio Ghezzi,
Sara Bertorello,
Marco Pallecchi,
Francesco Cei,
Giulia Nannini,
Elena Niccolai,
Giulia Bandini,
Gian Luca Bartolucci,
Matteo Ramazzotti,
Amedeo Amedei
Affiliations
Marco Matucci-Cerinic
13 Vita Salute San Raffaele University, Milan, Italy
Cosimo Bruni
1 Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
Gemma Lepri
1 Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
Martina Orlandi
10 Department of Medical and Surgical Sciences for Children, University of Modena and Reggio Emilia, Modena, Italy
Serena Guiducci
1 Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
Mirko Manetti
5 Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
Eloisa Romano
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Irene Rosa
5 Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
Silvia Bellando-Randone
2 Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy
Bianca Saveria Fioretto
5 Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
Khadija El Aoufy
6 Department of Health Sciences, University of Florence, Florence, Italy
Edda Russo
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Leandro Di Gloria
4 Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy
Simone Baldi
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Giulio Ghezzi
1 Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
Sara Bertorello
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Marco Pallecchi
8 Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
Francesco Cei
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Giulia Nannini
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Elena Niccolai
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Giulia Bandini
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Gian Luca Bartolucci
11 Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Florence, Italy
Matteo Ramazzotti
4 Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy
Amedeo Amedei
3 Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
Objectives In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc.Methods Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected. The GM was assessed through 16S rRNA sequencing, while SCFAs and FFAs were assessed by gas chromatography-mass spectrometry.Results In patients with VEDOSS, an increase in Bacteroidales and Oscillospirales orders and a decrease in Bacilli class, Blautia, Romboutsia, Streptococcus and Turicibacter genera was detected in comparison with HC. In patients with SSc, an elevated number of Acidaminococcaceae and Sutterellaceae families, along with a decrease of the Peptostreptococcaceae family and Anaerostipes, Blautia, Romboutsia and Turicibacter genera was found in comparison with HC. Patients with SSc and VEDOSS had a significantly lower butyrate and higher acetate with respect to HC. In VEDOSS, an increase in Oscillospiraceae family and Anaerostipes genus, and a decrease in Alphaproteobacteria class, and Lactobacillales order was identified with respect to SSc. Moreover, patients with VEDOSS exhibited higher acetate and lower valerate compared with definite SSc.Conclusion A GM dysbiosis with depletion of beneficial anti-inflammatory bacteria (especially butyrate-producing) and a significant decrease in faecal butyrate was identified in patients with VEDOSS. This early GM imbalance may foster the growth of inflammatory microbes, worsening intestinal dysbiosis and inflammation in early SSc stages. The potential butyrate administration in early disease phases might be considered as a novel therapeutic approach to mitigate gastrointestinal discomfort and progression preserving patient’s quality of life.
