The goal of this observational study is to evaluate the orointestinal microbiome and microbial derived metabolome in patients suffering from acute pancreatitis as a biomarker for severity. The main questions it aims to answer are: * Can the orointestinal microbiome robustly predict the course of acute pancreatitis? * How does the microbiome impact the severity of an acute pancreatitis? Buccal/ rectal swabs, plasma and stool is collected from patients with acute pancreatitis within 48h after hospital admission.
Despite intensive research, early prediction of the course of acute pancreatitis (AP) is still not satisfactorily possible. Results of a European multicenter study showed that the intestinal microbiome is superior to established scores as a marker of severity in patients with AP. Hereby, a classifier was established using 16 differentially abundant rectal species and systemic inflammatory response syndrome (SIRS) and achieved an AUROC of 85%. Surprisingly, all species in the severe AP group were members of taxonomic families known for their short-chain fatty acid (SFCA) production. This observation contrasts with translational pancreatitis studies in mice. Based on these publications, a clinical trial is currently being initiated to treat severe AP with SCFA (NCT06147635). However, previous well-designed RCT that analyzed the effects of probiotics in predicted severe AP resulted in a worse outcome for patients in the probiotic arm. Consequently, national and international guidelines recommend against the usage of probiotics in AP. Collectively, more research is needed to further elucidate the role of the oro-intestinal microbiota in the development of severe AP. To validate the results of previously mentioned multicenter study and to profoundly analyze the role of microbial metabolites and the fungeome, patients with AP will be prospectively recruited. 1. Buccal and rectal swabs, stool and plasma will be obtained to analyze the orointestinal microbiome and microbial derived metabolites. 2. Centers from different continents with different ethical background and dietary habits will enroll patients to gain a more generalizable microbial profile. 3. Microbial shifts were observed between severe AP (RAC 3) and mild/ moderate severe (RAC 1+2). 4. It is expected that the microbial compositions change during the inflammatory process upon early phase of pancreatitis. To minimize this microbial alternating effect a short time frame from hospital admission to recruitment (48h) is set.
Study Type
OBSERVATIONAL
Enrollment
700
University Medical Center Goettingen
Göttingen, Lower Saxony, Germany
RECRUITINGNovel microbiome species and/or functional metabolic pathways that are associated with the severity of acute pancreatitis
To assess the microbial diversity and differential abundances of species within buccal and rectal swabs analyzed by ONT sequencing followed by prediction of metabolic pathways and metabolites using tools such as Megan6 and GapSeq stratified by the Revised Atlanta Classification and severity (necrotic collections that require intervention and/or organ failure \>48h), adjusted for multiple individual confounders.
Time frame: until discharge (up to 90 days)
Classifier developed based on differentially regulated metabolites
To assess the metabolite (predicted in 1. Primary endpoint) levels in stool and plasma samples by targeted metabolomics to develop a classifier based on differentially regulated metabolites to assess its discriminatory power in predicting Revised Atlanta Classification and severity.
Time frame: Until discharge (up to 90 days)
Mortality
Association of mortality with microbial diversity and differential abundance and differentially regulated metabolites adjusted for multiple individual confounder. Long-term outcomes will be assessed in the current cohort (P-MAPS II), as well as in the previously established P-MAPS I cohort (NCT04777812).
Time frame: up to 1096 days (3 years)
Length of hospital stay
Association of length of hospital stay with microbial diversity and differential abundance and differentially regulated metabolites adjusted for multiple individual confounder.
Time frame: up to 90 days
Post-discharge exocrine and endocrine insufficiency
Association of post-discharge exocrine and endocrine insufficiency with microbial diversity and differential abundance and differentially regulated metabolites adjusted for multiple individual confounder. Long-term outcomes will be assessed in the current cohort (P-MAPS II), as well as in the previously established P-MAPS I cohort (NCT04777812).
Time frame: up to 90 days
Post-discharge re-intervention
Association of post-discharge re-intervention with microbial diversity and differential abundance and differentially regulated metabolites adjusted for multiple individual confounder. Long-term outcomes will be assessed in the current cohort (P-MAPS II), as well as in the previously established P-MAPS I cohort (NCT04777812).
Time frame: up to 1096 days (3 years)
Recurrent/chronic pancreatitis rate
Association of recurrent/chronic pancreatitis rate with microbial diversity and differential abundance and differentially regulated metabolites adjusted for multiple individual confounder. Long-term outcomes will be assessed in the current cohort (P-MAPS II), as well as in the previously established P-MAPS I cohort (NCT04777812).
Time frame: up to 1096 days (3 years)
Volatile organic compounds
Assessment of volatile organic compounds (VOCs) in a subset of the study cohort (n = 60), including group comparisons based on the revised Atlanta classification and severity, as well as correlation of VOC concentrations with corresponding plasma levels.
Time frame: Until discharge (up to 90 days)
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