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P267 Relationship between morphological alteration of paneth cells and dysbiosis in patients with inflammatory bowel disease

K. Nagashima*1, K. Nakamura2, T. Katsurada1, Y. Shimizu2, Y. Yokoi2, S. Otagiri1, K. Yamanashi1, K. Kinoshita1, R. Onishi1, N. Sakamoto1, T. Ayabe2

1Hokkaido University Faculty of Medicine and Graduate School of Medicine, Division of Endoscopy/Department of Gastroenterology and Hepatology, Sapporo, Japan, 2Hokkaido University, Faculty of Advanced Life, Science Graduate School of Life Science, Department of Cell Biological Science, Sapporo, Japan

Background

Inflammatory bowel disease (IBD) is broadly categorised into Crohn’s disease (CD) and ulcerative colitis (UC). The causal factors underlying IBD pathology remain unclear, however a relationship between microbiota and intestinal immunity is one of pathological factors. Paneth cell is a key player in innate gut immunity, and reported to contribute to the pathogenesis of CD, whereas the association between Paneth cell and UC remains unclear.

The aims of this study were therefore to verify whether measurements of the granule diameter of Paneth cells corresponding to Paneth cell morphology using biopsy samples could be used clinically as a pathological evaluation tool and to clarify the relationship between Paneth cells and intestinal microbiota in IBD by conducting 16S rRNA sequencing of intestinal bacteria in stool samples collected from the same patients at the same time.

Methods

Endoscopic biopsy specimens and stool samples were collected from 20 patients with each condition treated at Hokkaido University Hospital. Controls included stool samples from 20 volunteers and endoscopic biopsy specimens from 20 non-IBD cases. Paneth cell morphology evaluation in biopsy specimens focussed on pathological granule aspects; stool samples underwent 16S rRNA sequencing of microbiota.

Results

Paneth cell granule diameter was significantly smaller, and atypical Paneth cell proportions was significantly larger in the CD group. Stool samples of the CD group showed dysbiosis with significantly reduced intestinal microbiota α diversity, with a low degree of β diversity similarity. Firmicutes, Clostridiales, Ruminococcae, and Faecalibacterium were significantly reduced, whereas Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Bacteroides were increased. Conversely, a lower degree of β diversity similarity was observed in the UC group than Control groups. Clostridiales, Lachnospiraceae, Faecaribacterium, and Coprococcus were significantly reduced, whereas Bacilli and Lactobacillales were significantly increased. For the CD group, Paneth cell granule diameter positively correlated with Clostridiales occupancy, whereas Paneth cell morphology did not correlate with microbiota in the UC group.

Conclusion

Paneth cells with altered granular morphology i.e., having smaller granules were found only in the CD group, and the alteration correlated with dysbiosis, indicating that Paneth cells are strongly involved in the pathology of CD. In contrast, no correlation was found in the UC group between the morphological changes of Paneth cells and dysbiosis, suggesting that major factors contributed to dysbiosis in UC might not be Paneth cells. Our results further suggested that the cause of dysbiosis in UC may differ from that of CD.