RT Journal Article
SR Electronic
T1 Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 915
OP 927
DO 10.1136/gutjnl-2019-320430
VO 70
IS 5
A1 Fons F van den Berg
A1 Demi van Dalen
A1 Sanjiv K Hyoju
A1 Hjalmar C van Santvoort
A1 Marc G Besselink
A1 Willem Joost Wiersinga
A1 Olga Zaborina
A1 Marja A Boermeester
A1 John Alverdy
YR 2021
UL http://gut.bmj.com/content/70/5/915.abstract
AB Objective The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.Design C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.Results Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Escherichia coli and an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.Conclusion Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.Data are available upon reasonable request.