Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease.
The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study.



Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by1H nuclear magnetic resonance.



Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion ofClostridiumcluster IV.Clostridiumcluster IX,Fusobacteriumand Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosalClostridiumcluster IV andAkkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy.



Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease.
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Giovanni
G
Barbara
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Eleonora
E
Scaioli
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Maria Raffaella
MR
Barbaro
Department of Pharmacy and Biotechnology, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Elena
E
Biagi
Department of Agri-Food Sciences and Technologies, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Luca
L
Laghi
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Cesare
C
Cremon
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Giovanni
G
Marasco
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Antonio
A
Colecchia
Department of Agri-Food Sciences and Technologies, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Gianfranco
G
Picone
Pathology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Nunzio
N
Salfi
Department of Agri-Food Sciences and Technologies, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Francesco
F
Capozzi
Department of Pharmacy and Biotechnology, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Patrizia
P
Brigidi
Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Davide
D
Festi
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D003106:Colon / Q000378:metabolism; D003430:Cross-Sectional Studies; D043963:Diverticulosis, Colonic / Q000378:metabolism* / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D055442:Metabolome; D008875:Middle Aged; D010865:Pilot Projects
COLONIC MICROFLORA; COLONIC MUCOSAL METABOLISM; DIVERTICULAR DISEASE; INTESTINAL MICROBIOLOGY; MACROPHAGES