Investigating microbiota differences across chronic pancreatitis, influenced by lifestyle and genetic determinants

Background: Chronic pancreatitis (CP) is a multifaceted and irreversible inflammatory condition that impacts both endocrine and exocrine pancreatic functions. Whilst there is evidence of a general intestinal microbial dysbiosis, differences across CP resulting from diverse triggers remains poorly elucidated. Methods: In this study, we investigated how different CP triggers, namely alcohol-induced CP (AIP) and CFTR-related CP (CFRP), might undermine differences across microbiota structure and predicted function. Faecal samples from 25 CP participants were collected, alongside 9 healthy controls for microbiota analyses. Both full and short (V4) 16S rRNA sequencing was performed, including predicted functionality using PICRUSt2. Clinical metadata was integrated to investigate relationships with microbiota structure and predicted functionality with ordination-based approaches. Results: Microbiota diversity patterns between groups varied slightly by sequencing approach, with differences across common core and rarer satellite taxa diversity evident. Importantly, microbiota compositional profiles were shared between approaches, with control samples clustering closer than CP samples. Between groups, significant differences in microbiota composition were apparent, with the AIP group significantly different to both control and CFRP groups across various microbiota partitions (P < 0.05). Notable genera drove the observed dissimilarity, including Bifidobacterium, Faecalibacterium, and Ruminococcus, which were decreased in relative abundance across CP. Predictive functional analyses further demonstrated increased similarity of controls as compared to CP groups. Significant variation across both microbiota structure and predicted function was explained by CP subtype (P < 0.01). When compared back to controls, the relative abundance of various predicted functional pathways from both the core and satellite taxa was significantly different across groups (P < 0.05). Conclusions: Overall, we demonstrate that gut microbiota structure and predicted function differs between not only healthy controls and CP but across CP subtypes themselves. Various taxa with important physiological roles were implicated across CP. Differences in predicted functionality of the core and satellite taxa were evident, relating to microbial processes that may have downstream consequences at the site of the GI tract. Future studies will employ larger cohorts with the incorporation of additional omics-based approaches. This will better elucidate differences in microbiota structure and functionality across CP, including relationships with pancreatic-based clinical outcomes.