P081 The integration of transcriptomic and microbiomic data links several intestinal bacterial families with key biological functions in the development of postoperative recurrence in Crohn's disease

• Published in: Journal of Crohn's and colitis Vol. 18; no. Supplement_1; pp. i355 - i356
• Main Authors: Cabrer, M, Suau, R, Lopez-Siles, M, Martinez-Medina, M, Aterido, A, Julià, T, Zabana, Y, Calafat, M, Clua, L, Lorén, V, Domènech, E, Mañosa, M, Manyé, J
• Format: Journal Article
• Language: English
• Published: 24.01.2024
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjad212.0211

Abstract Background Crohn's disease (CD) is characterized by an imbalance between the microbiota and the host. The severity of CD leads to intestinal resection. However, more than half of the patients not receiving prophylaxis experience post-operative recurrence (POR) within one year. The main objective of this study has been to improve the knowledge of the pathophysiological bases of POR through the integration of transcriptome and microbiome data. Methods Samples of inflamed and microscopically non-inflamed ileal mucosa were collected from patients with CD undergoing intestinal resection. The severity of POR was classified according to the Rutgeerts endoscopic index: without recurrence (i0+i1, n=12) and with recurrence (i2+i3+i4, n=8). Samples of healthy ileal tissue were also obtained from patients with colorectal cancer (n=10). Gene expression was evaluated by microarrays and organized into co-expression modules. By sequencing the V3-V4 region of the 16S rRNA gene, intestinal bacteria were identified and classified at the genus and family taxonomic level. The differential expression and correlations between the two sources of omics information were studied. Next, the analysis of pathway enrichment and clustering was carried out according to the severity of the POR and the intestinal area affected or not (graphical abstract A). Results The results of the integrative analysis in the uninflamed area of patients without recurrence showed that Actinomycetales negatively correlated with COX6A1 and MTRF1L, related to mitochondrial respiration (GO:0098803; q=0.004) and protein synthesis (R-HSA-72766; q=0.034) (B). These genes and bacteria also played a key role in modules 3 and 25 related to the respiratory chain. In contrast, the inflamed area of recurrent patients showed a positive correlation of the Xanthomonadaceae family in the regulation of neutrophil granules (GO:0035579; q=0.011), with the key participation of the ITGAM transcript (C). This transcript was also related to integrins (R-HSA-216083; q=0.007) in the transcriptomic analyses. In addition, Porphyromonadaceae correlated with LSR and TFF1, involved in epithelium maintenance (GO:0010669; q=0.012) and A group in the Lachnospiradaceae family correlated with CDC20 and CDT1, linked to the cell cycle (q=0.019). Conclusion Bacterial families, involved in butyrate production, such as Porphyromonadaceae and Lachnospiradaceae, could influence functions that remember to epithelial regeneration in recurrent patients, while Actinomycetales are associated with a normalization in energy production in uninflamed areas of resections of patients without POR. These findings reveal a potential interaction between the microbiota and the pathophysiology of POR in patients with CD.