Small Intestinal Bacterial Overgrowth Is Common in Chronic Pancreatitis and Associates With Diabetes, Chronic Pancreatitis Severity, Low Zinc Levels, and Opiate Use

Abstract

Objectives: Small intestinal bacterial overgrowth (SIBO) is often present in patients with chronic pancreatitis (CP) with persistent steatorrhea, despite pancreatic enzyme replacement therapy. Overall prevalence of SIBO, diagnosed by glucose breath test (GBT), varies between 0% and 40% but 0%-21% in those without upper gastrointestinal (GI) surgery. We investigated the prevalence and nonsurgical independent predictors of SIBO in CP without upper GI surgery.

Methods: Two hundred seventy-three patients ≥18 years old had a presumptive diagnosis of CP and a GBT between 1989 and 2017. We defined CP by Mayo score (0-16) ≥4 and a positive GBT for SIBO by Rome consensus criteria and retrospectively collected data for 5 a priori variables (age, opiates, alcohol use, diabetes mellitus (DM), gastroparesis) and 41 investigational variables (demographics, GI symptoms, comorbidities, CP etiologies and cofactors, CP symptom duration, Mayo score and nondiabetes components, and biochemical variables).

Results: Ninety-eight of 273 patients had definite CP and 40.8% had SIBO. Five of 46 variables predicted SIBO: opiates, P = 0.005; DM, P = 0.04; total Mayo score, P < 0.05; zinc, P = 0.005; and albumin, P < 0.05). Multivariable analysis of 3 noncorrelated variables identified zinc level (odds ratio = 0.0001; P = 0.03) as the sole independent predictor of SIBO (model C-statistic = 0.89; P < 0.001).

Discussion: SIBO, diagnosed by GBT, occurs in 40.8% of patients with CP without upper GI surgery. In patients with CP, markers of more severe CP (low zinc level, DM and increased Mayo score) and opiate use should raise clinical suspicion for SIBO, particularly in patients with persistent steatorrhea or weight loss despite pancreatic enzyme replacement therapy.

Figure 1.

Methodological Summary

Figure 2.. Mayo Clinical Diagnostic Criteria: A Scoring System for Definite Chronic Pancreatitis

CCK, cholecystokinin; FBG, Fasting Blood Glucose; PFT, pancreatic function testing; RAP, Recurrent Acute Pancreatitis; EUS, Endoscopic Ultrasonography *EUS criteria for CP included having > 5 EUS criteria or EUS Rosemont criteria that were suggestive of or consistent with CP **Pancreatic steatorrhea was based on a positive qualitative fecal fat or quantitative fecal fat >7 grams/24 hours Adapted from (45).

Figure 3.. ROC curve for two related models of SIBO in definite CP by multivariable logistic regression

a) Area under the ROC curve for model #1 which included 3 variables: diabetes mellitus (DM), zinc level, and opiate use. This model of SIBO in patients with definite CP had a significant negative association with zinc (OR=0.0001, p=0.03), a positive but non-significant association with DM (OR=8.23, p=0.08) and a C-statistic of 0.89 (95% CI 0.76–1.00). b) ROC curve for model #2 which included 3 variables: total Mayo clinical score, zinc level, and opiate use. This model of SIBO in definite CP showed a significant negative association with zinc (OR=0.0001, p=0.04), no positive association with Mayo score, and a C-statistic of 0.88 (95% CI 0.74–1.00).