The Jejunal Microbiota in Patients With Chronic Pancreatitis: Results From a Pilot Study

Chronic pancreatitis (CP) is associated with several systemic metabolic abnormalities including diabetes. While the colonic microbiota and its association with diabetes in CP have been reported, the specific composition of the small intestinal microbiota and its function in CP remains poorly understood. In this pilot study, we primarily aimed to characterize the jejunal microbiota in patients with CP and explore potential associations with diabetes.

Jejunal aspirates were collected in a RNAlater-containing sterile container from 29 patients with CP and 10 controls. The samples were then snap lysed followed by metagenomic DNA extraction. Next-generation sequencing was performed for the variable region 3-4 of the 16SrDNA in Illumina MiSeq. After quality control, microbial profiling and functional analysis were conducted using standard bioinformatics pipelines. We also evaluated tight junction integrity in jejunal biopsy samples using immunofluorescence. Furthermore, we assessed for plasma and stool metabolites.

Patients with CP exhibited higher abundances of Prevotella vespertina, Prevotella oris, and Prevotella salivae, while controls demonstrated higher abundances of Prevotella scopos, Veillonella, Rothia, and Lachnospiraceae. Immunofluorescence showed decreased expression of the tight junction protein occludin in the jejunal mucosa of CP diabetic (CPD) patients compared to endoscopic controls (EC) (p.corr. CPD-EC = 0.012). No differences were seen between CP nondiabetic and endoscopic controls, and between the CP subgroups (CPND-EC = 0.29 and CPD-CPND = 1 respectively). Overall, there were significant plasma metabolomic abnormalities in patients with CP and a trend toward reduction of butyrate in the stool samples of the CP patients with diabetes.

Our observations suggest alterations in the jejunal microbiota and mucosal barrier function in CP. These were associated with lower fecal butyrate. This may contribute to the pathogenesis of associated metabolic complications in CP. Further large-scale longitudinal and mechanistic studies are needed to validate our findings.