AUTHOR=Russo Edda , Cinci Lorenzo , Di Gloria Leandro , Baldi Simone , D’Ambrosio Mario , Nannini Giulia , Bigagli Elisabetta , Curini Lavinia , Pallecchi Marco , Andrea Arcese Donato , Scaringi Stefano , Malentacchi Cecilia , Bartolucci Gianluca , Ramazzotti Matteo , Luceri Cristina , Amedei Amedeo , Giudici Francesco 

TITLE=Crohn’s disease recurrence updates: first surgery vs. surgical relapse patients display different profiles of ileal microbiota and systemic microbial-associated inflammatory factors

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.886468

DOI=10.3389/fimmu.2022.886468

ISSN=1664-3224

ABSTRACT=<sec><title>Background and aims</title><p>Crohn’s disease (CD) pathogenesis is still unclear. Remodeling in mucosal microbiota and systemic immunoregulation may represent an important component in tissue injury. Here, we aim to characterize the ileal microbiota in both pathological and healthy settings and to evaluate the correlated systemic microbial-associated inflammatory markers comparing first-time surgery and relapse clinical conditions.</p></sec><sec><title>Methods</title><p>We enrolled 28 CD patients at surgery; we collected inflamed and non-inflamed mucosa tissues and blood samples from each patient. Bacterial wall adherence was observed histologically, while its composition was assessed through amplicon sequencing of the 16S rRNA gene. In addition, we evaluated the systemic microRNA (miRNA) using quantitative real-time PCR amplification and free fatty acids (FFAs) using gas chromatography–mass spectroscopy.</p></sec><sec><title>Results</title><p>The total number of mucosal adherent microbiota was enriched in healthy compared to inflamed mucosa. In contrast, the phylum <italic>Tenericutes</italic>, the family <italic>Ruminococcaceae</italic>, and the genera <italic>Mesoplasma</italic> and <italic>Mycoplasma</italic> were significantly enriched in the pathological setting. Significant microbiota differences were observed between the relapse and first surgery patients regarding the families <italic>Bacillaceae 2</italic> and <italic>Brucellaceae</italic> and the genera <italic>Escherichia/Shigella</italic>, <italic>Finegoldia</italic>, <italic>Antrobacter</italic>, <italic>Gemmatimonas</italic>, <italic>Moraxella</italic>, <italic>Anoxibacillus</italic>, and <italic>Proteus</italic>. At the systemic level, we observed a significant downregulation of circulating miR-155 and miR-223, as well as 2-methyl butyric, isobutyric, and hexanoic (caproic) acids in recurrence compared to the first surgery patients. In addition, the level of hexanoic acid seems to act as a predictor of recurrence risk in CD patients (OR 18; 95% confidence interval 1.24–261.81; <italic>p</italic> = 0.006).</p></sec><sec><title>Conclusions</title><p>We describe a dissimilarity of ileal microbiota composition comparing CD and healthy settings, as well as systemic microbial-associated inflammatory factors between first surgery and surgical relapse. We suggest that patterns of microbiota, associated with healthy ileal tissue, could be involved in triggering CD recurrence. Our findings may provide insight into the dynamics of the gut microbiota–immunity axis in CD surgical recurrence, paving the way for new diagnostics and therapeutics aimed not only at reducing inflammation but also at maintaining a general state of eubiosis in healthy tissue.</p></sec>