P110 GUT MICROBIOTA CHANGES DIRECLTY INDUCED BY IL-1α NEUTRALIZATION LEAD TO REDUCTION OF ILEITIS AND DSS-INDUCED COLITIS IN SAMP1/YITFC MICE

• Published in: Inflammatory bowel diseases 2019-02, Vol.25 (Supplement_1), p.S55-S55
• Main Authors: Menghini, Paola, Buttò, Ludovica F, Osme, Abdullah, Rodriguez-Palacios, Alexander, Cominelli, Fabio
• Format: Article
• Language: English
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1093/ibd/izy393.120

Abstract Background We have previously shown that neutralization of IL-1α with a specific murine monoclonal antibody (FLO1) in 25-wk old SAMP1/YitFc (SAMP) mice with established CD-like ileitis, ameliorates ileitis severity. These results were associated with gut microbiome alterations. However, whether these effects are a consequence of decreased intestinal inflammation or a direct effect of FLO1 is unknown. Here, we treated inflammation-free SAMP mice (4-wk old) with FLO1 to confirm that this antibody modulates the gut microbiome in the absence of inflammation; secondly, we ought to test whether treated mice are more resistant to DSS-induced colitis. Methods FLO1-treated (100μg; 2x/wk for 4 wks) 4-wk old SAMP mice were compared to age/gender-matched SAMP treated with dexamethasone (Dex, 1mg/kg/day for 1 wk) or untreated SAMP controls (Ctrl). Mice were then challenged with 3% DSS for 1 wk. After 2-wk recovery, mice were euthanized and colons were collected for histological assessment of intestinal inflammation and myeloperoxidase (MPO). Microbiota composition, prior and post treatment, was monitored with 16s rRNA analysis of collected stool samples. Results FLO1-treated mice displayed higher resistance to DSS treatment with lower mortality rate and decreased inflammatory scores (Ctrl=8.22 ± 1.15; Dex=7.5 ± 1.2; FLO1=4.9 ± 0.66; P=0.045) vs Dex and Ctrl groups. Weight loss was decreased in FLO1-treated SAMP compared to the other groups (P≥0.02). Accordingly, the MPO activity in colon samples from FLO1-treated SAMP mice was decreased vs Dex-treated and Ctrl mice (Ctrl=82.94 ± 7.3; Dex=74.34 ± 12; FLO1=55.55 ± 6.9; P=0.035). Data obtained by multinomial logistic regression analysis of significant species, controlling for experimental replica, and fragmented with at least 6 other ranked co-abundant taxa, revealed significant treatment-related changes in Mucispirillum schaedleri and Lactobacillus salivarius species. These taxa displayed a higher relative risk ratio in FLO1-treated vs Ctrl mice (Padj≤0.03). Of interest, Helicobacter hepaticus was significantly inhibited in FLO1–treated mice compared to both Ctrl and Dex groups (Padj≤0.003). These results suggest that FLO1 treatment in young SAMP mice directly alters gut microbiome composition, generating an anti-inflammatory microbiota. Conclusion Our findings strongly suggest that IL-1α neutralization protects SAMP mice from ileitis and DSS colitis, by a mechanism involving a direct modulation of the gut micro