Metaproteomics reveals diet-induced changes in gut microbiome function according to Crohn’s disease location
Stefano Levi Mortera,
Valeria Marzano,
Federica Rapisarda,
Chiara Marangelo,
Ilaria Pirona,
Pamela Vernocchi,
Marta Di Michele,
Federica Del Chierico,
Maria A. Quintero,
Irina Fernandez,
Hajar Hazime,
Rose M. Killian,
Norma Solis,
Mailenys Ortega,
Oriana M. Damas,
Siobhan Proksell,
David H. Kerman,
Amar R. Deshpande,
Luis Garces,
Franco Scaldaferri,
Antonio Gasbarrini,
Maria T. Abreu,
Lorenza Putignani
Affiliations
Stefano Levi Mortera
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Valeria Marzano
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Federica Rapisarda
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Chiara Marangelo
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Ilaria Pirona
GenomeUp SRL
Pamela Vernocchi
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Marta Di Michele
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Federica Del Chierico
Immunology, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Maria A. Quintero
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Irina Fernandez
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Hajar Hazime
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Rose M. Killian
John P. Hussman Institute for Human Genomics, University of Miami
Norma Solis
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Mailenys Ortega
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Oriana M. Damas
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Siobhan Proksell
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
David H. Kerman
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Amar R. Deshpande
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Luis Garces
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Franco Scaldaferri
Istituto Di Patologia Speciale Medica, Catholic University of the Sacred Heart
Antonio Gasbarrini
Istituto Di Patologia Speciale Medica, Catholic University of the Sacred Heart
Maria T. Abreu
Division of Gastroenterology, Department of Medicine, Miller School of Medicine, University of Miami
Lorenza Putignani
Department of Diagnostics and Laboratory Medicine, Microbiology and Diagnostic Immunology Unit, Microbiomics and Immunology Unit, Rheumatology and Infectious Disease Research Area, Human Microbiome Unit, Bambino Gesù Children’s Hospital, IRCCS
Abstract Background Crohn’s disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry. Results At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs. Conclusions The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract
