TY - JOUR
T1 - Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate
AU - van den Berg, Fons F
AU - van Dalen, Demi
AU - Hyoju, Sanjiv K
AU - van Santvoort, Hjalmar C
AU - Besselink, Marc G
AU - Wiersinga, Willem Joost
AU - Zaborina, Olga
AU - Boermeester, Marja A
AU - Alverdy, John
N1 - Publisher Copyright:
© 2021 Author(s) (or their employer(s)).
PY - 2021/5
Y1 - 2021/5
N2 - 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.
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.
KW - acute pancreatitis
KW - antibiotics
KW - bacterial infection
KW - butyrate
KW - diet
UR - http://www.scopus.com/inward/record.url?scp=85090843078&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2019-320430
DO - 10.1136/gutjnl-2019-320430
M3 - Article
C2 - 32873697
SN - 0017-5749
VL - 70
SP - 915
EP - 927
JO - Gut
JF - Gut
IS - 5
M1 - gutjnl-2019-320430
ER -