Duodenal Fluid Microbiome Diversity and Pancreatic Cyst Status Among Patients Undergoing Pancreatic Surveillance

Pancreatic cancer is associated with alterations in the gut microbiome; whether these changes are a cause or consequence of the disease is not known. This study aimed to compare the gut microbiome of patients with precancerous pancreatic cysts to that of patients without cysts.

Case/control analysis of 492 patients undergoing pancreatic surveillance, 267 patients with pancreatic cyst(s) and 225 without. Duodenal fluid bacterial DNA collected during endoscopic ultrasound was amplified and sequenced (16S ribosomal RNA). Measures of alpha and beta diversity were stratified by pancreatic cyst status, adjusting for demographic and clinical factors.

Duodenal fluid alpha diversity measures were significantly lower in patients with pancreatic cysts compared to those without, with no significant differences between patients with small vs large pancreatic cysts, or those with worrisome features. Multivariate analysis revealed that measures of alpha diversity (Shannon index, operational taxonomic units, Faith phylogenetic diversity) were independently associated with having a pancreatic cyst: (Shannon index; adjusted odds ratio/95% confidence interval; 0.59/0.45-0.76, P < 01), along with diabetes status (2.35/1.2-4.79, P < .01) and age ≥75 years (2.72/1.43-5.50, P < .002). Duodenal fluid beta diversity differed significantly by covariates, including older age, proton pump inhibitor use, diabetes, current smoking, and regular alcohol use. In patients without these cofactors, duodenal fluid beta diversity did not differ significantly by pancreatic cyst status.

Patients undergoing pancreas surveillance who have pancreatic cysts have lower duodenal fluid alpha diversity compared to those without cysts. Further study is needed to determine if gut microbiome profiles predict future cancer risk in patients undergoing pancreas surveillance.