Additional file 2 of Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease
Creators: name: Chevalier, Grégoire
name: Laveissière, Arnaud
name: Desachy, Guillaume
name: Barnich, Nicolas
name: Sivignon, Adeline
name: Maresca, Marc
name: Nicoletti, Cendrine
name: Di Pasquale, Eric
name: Martinez-Medina, Margarita
name: Simpson, Kenneth William
name: Yajnik, Vijay
name: Sokol, Harry
name: Plassais, Jonathan
name: Strozzi, Francesco
name: Cervino, Alessandra
name: Morra, Rachel
name: Bonny, Christophe
Publisher: name: figshare
Year: 2021
Subjects: subject: Microbiology
subject: FOS: Biological sciences

description: Additional file 1: Supplementary Table 1. Demographic data and history of Crohn’s Disease of the patients with CD included in each of the presented studies. *: Montreal classification for Cohort 1 and 3. **: MOBIDIC: QUANTA Lite/LLOD=15.6mg/kg. CrohnOmeter: Bühlmann/LLOD=50mg/kg. PREDICT: Bühlmann/LLOD=30mg/kg. NA=Not available. Supplementary Table 2. Demographic data of the healthy volunteers included in the presented study. Supplementary Table 3. Median values for Enterobacteriaceae species in Fig. 2c (top table) and d (bottom table). Supplementary Table 4. List of isolated E. coli strains and associated information. Supplementary Figure 1. Evolution over time of the first cohort regarding HBI (left) and E. coli relative abundance (right). A linear mixed model was used to identify statistically significant differences between time points (visits) and did not reach significance for E. coli abundance (P = 0.51) nor for HBI (P = 0.41). Supplementary Figure 2. Some Proteobacteria express FimH adhesin. Cladogram representing the bacteria phyla detected in the human gut microbiome (left) and FimH presence with a focus on Enterobacteriaceae spp (right). Supplementary Figure 3. Dichotomy in patient with CD from Cohort 2. a, Microbial clustering as shown based on Bray–Curtis dissimilarity principal Coordinate Analysis (PCoA) metrics for HV and patients with CD from Cohort2 with PC1 ≤ 0.1 and PC1 &gt; 0.1. Ellipsoids represent a 95% confidence interval surrounding each group. b, Relative abundance of Enterobacteriaceae spp in HV and patients with CD from Cohort2 with PC1 ≤ 0.1 and PC1 &gt; 0.1. Non-parametric Mann-Whitney U test was used to identify the statistically significant differences between groups. (* P &lt; 0.05, ** P &lt; 0.005, **** P &lt; 0.0001). Supplementary Figure 4. Structure of the bi-mannosylated FimH-blocker TAK-018. Supplementary Figure 5. Association between percentage of FimS-ON expression and aggregation to TAK-018 of different AIEC strains. The mapping against the fimS region revealed a strong association between the percentage of reads in the “ON” position, indicative of expression of the entire fim operon, and the aggregation to TAK-018. Median are represented. Non-parametric Mann-Whitney U test was used to identify the statistically significant differences between groups (n.s. non-significant, *** P &lt; 0.0005, **** P &lt; 0.0001). Supplementary Figure 6. TAK-018 prevents adhesion of LF82 E. coli to T84 intestinal epithelial cells in a FimH-dependent manner. Bars represent the mean value of individual points which themselves correspond to biological replicates. A non-parametric Kruskal-Wallis test was used to identify the statistically significant differences between the LF82 groups (P = 0.0002). Supplementary Figure 7. TAK-018 prevents pro-inflammatory cytokine secretion of human ileal explants upon incubation with LF82 E. coli. IL-6 and IL-8 secretion of human ileal explants incubated for 4 hours with 109 LF82 E. coli, in the presence of increasing concentrations of TAK-018. IL-1β was used as a positive control to trigger inflammation. Bars represent the mean value of individual points which themselves correspond to biological replicates. A linear mixed model was used to identify statistically significant differences between the groups No TAK-018, TAK-018 500nM and TAK-018 1µM (IL-6, P = 0.1; IL-8, P = 0.0006). Supplementary Figure 8. TAK-018 prevents adhesion of LF82 E. coli to primary human intestinal cells isolated from patient with Crohn’s disease. Microscopy images of GFP LF82 E. coli (green) on primary human ileal cells stained with phalloidin Alexa-547 (red) in presence of TAK-018 (bottom) or not (top).