Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis

doi:10.1016/j.pan.2015.07.005

Pancreatology

Volume 15, Issue 5, September–October 2015, Pages 514-518

https://doi.org/10.1016/j.pan.2015.07.005 Get rights and content

Abstract

Backgrounds

The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis.

Methods

36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H₂)–methane (CH₄) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H₂ (≥20 ppm) or CH₄ (≥10 ppm) over the baseline or (2) a baseline H₂ (≥20 ppm) or CH₄ (≥10 ppm) within 90 min after lactulose load.

Results

LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H₂ levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H₂)+, (CH₄)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT− group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT− group The laboratory and radiologic features were not significantly different between LBT+ and LBT− groups.

Conclusions

SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H₂ and CH₄ appear to be related with deterioration of intestinal symptoms.

Introduction

Chronic pancreatitis (CP) is a multiple etiological disease characterized by abdominal discomfort, diarrhea and maldigestion. Current guidelines recommend oral pancreatic enzyme replacement therapy for patients with CP with maldigestion and intestinal symptoms. However, many patients with CP continue to suffer from abdominal symptoms and malnutrition despite an adequate pancreatic enzyme replacement. This reveals that the complex and multifactorial mechanisms are involved in the pathogenesis of intestinal symptoms in CP. One hypothesized mechanism is small intestinal bacterial overgrowth (SIBO) that provokes chronic symptoms such as abdominal discomfort, bloating, diarrhea, and malabsorption, similar to those observed in CP. Also, some clinical studies demonstrated that SIBO is often seen in patients with CP [1], [2], [3], [4].

SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the small bowel. Culture of jejunal aspirate is considered the gold standard test for SIBO diagnosis, but it is invasive and expensive. Thus recently, breath test is preferred, because it is simple, non-invasive and less expensive. The breath test is based on the concept that hydrogen (H₂) and methane (CH₄) generated in the intestine transfer through the intestinal wall into the bloodstream, then enters the lungs and is excreted in the breath. Increase of H₂ excretion has been commonly considered as a diagnosis of SIBO in clinical practice. However, around 30% of the general population has predominant methanogenic bacteria and produce methane as a main byproduct of carbohydrate fermentation [5]. Therefore, the addition of CH₄ to H₂ measurement may avoid false-negative results.

In consecutive studies, the prevalence of SIBO in patients with CP was found to be higher than in healthy subjects, but most studies used the simple H₂ breath test which cannot be enough to determine a SIBO. The aim of this study was to investigate the prevalence of SIBO using combined H₂ and CH₄ breath test with lactulose in patients with CP compared with controls without CP. We also evaluated the gas excretion patterns and their associations with clinical symptoms.

Section snippets

Materials and methods

This study was approved by the Institutional Research Ethics Board of the Catholic University of Korea (VC15RISI0064) and adhered to the declaration of Helsinki.

Study populations

Forty three patients were initially enrolled in the study. Among them, 7 patients were excluded due to abdominal surgery (n = 2, 1 gastrectomy, 1 pancreatectomy), gastrointestinal disease (n = 1, pancreatic cancer), the use of narcotics (n = 2), incompletion of data (n = 1), and sample error (n = 1). A total of 36 patients were finally enrolled in the analysis. The mean age of the patients was 52.3 years (range: 25–78 years) and 28 patients (77.8%) were men. The etiology of pancreatitis was

Discussion

This study showed that the LBT positivity is not uncommon in patients with CP. The LBT positivity indicate that SIBO might be correlated with intestinal symptoms in CP. Especially in the mixed H₂ and CH₄ excretors diagnosed by LBT, these gases may contribute to worsening intestinal symptoms.

The overall positivity to LBT in patients with CP was 47.2% (17/36) in our study. The suggested pathophysiologic mechanisms of SIBO in CP are reduced secretion of antibacterial pancreatic juice, the impaired

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The consequences of dysbiosis in pancreatic diseases remain unclear, with a limited body of evidence suggesting that there may be an association between dysbiosis and pancreatic disease; however, some of the studies show contradictory results. Regarding acute and chronic pancreatitis, data are scarce, but dysbiosis appears to be present in both conditions. Some studies show lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. One study shows higher levels of Enterococcus and lower levels of Bifidobacterium in acute pancreatitis. There is stronger evidence of a link between microbiota imbalance and pancreatic cancer. There is an overall association between pancreatic cancer and lower levels of Neisseria elongate and Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens. However, further investigation is required to confirm these findings, and to explore clinical implications such as screening and therapeutic possibilities.
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Citation Excerpt :
Of these, only two utilised the recommended glucose substrate [15,25]. The two studies that used lactulose substrate had notably higher prevalence of SIBO 69.9% [17] and 47.2% [24]. The prevalence of SIBO in the studies using glucose substrate (GHBT) was 0%–21% [15,25].
Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls.
Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated.
SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of ‘weight loss’, with patients reporting weight loss more likely to have SIBO (P = 0.047).
The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom treatment.
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Several studies have suggested a link between microbiota imbalance and some gastrointestinal, inflammatory and neoplastic diseases. However, the role in pancreatic diseases remain unclear. To evaluate the available evidence for pancreatic diseases, we undertook a systematic review.
OVID Medline (1946–2017), EMBASE (1980–2017) and the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2017) were searched for studies on microbiota in pancreatic disease. We also searched the reference lists of retrieved papers, and conference proceedings. We excluded animal studies, reviews, and case reports.
A total of 2833 articles were retrieved. After screening and applying the exclusion criteria, 10 studies were included. Three studies showed lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. Two of these studies were uncontrolled, and the third (controlled) study which compared patients with endocrine and exocrine insufficiency, reported that Bacteroidetes levels were lower in those patients without diabetes, while Bifidobacteria levels were higher in those without exocrine insufficiency. Only one study investigated acute pancreatitis, showing higher levels of Enterococcus and lower levels of Bifidobacterium versus healthy participants. There was an overall association between pancreatic cancer and lower levels of Neisseria elongate, Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens.
Current evidence suggests a possible link between microbiota imbalance and pancreatic cancer. Regarding acute and chronic pancreatitis, data are scarce, dysbiosis appears to be present in both conditions. However, further investigation is required to confirm these findings and to explore therapeutic possibilities.
Towards the Highest Sensitivity and Selectivity of the Earth's and Space's Laser-Based Methane Sensors
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Original articleBreath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis

Abstract

Backgrounds

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Study populations

Discussion

Pancreatology

Gastroenterology

Clin Gastroenterol Hepatol

Am J Gastroenterol

Small intestine bacterial overgrowth in patients with chronic pancreatitis

Rev Med Chil

Small intestinal bacterial overgrowth in patients with chronic pancreatitis

J Clin Gastroenterol

Morphological and functional alterations of small intestine in chronic pancreatitis

JOP

Small intestinal bacterial overgrowth: A framework for understanding irritable bowel syndrome

JAMA

The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications ofthe disease

J Gastroenterol

The characteristics of the positivity to the lactulose breath test in patients with abdominal bloating

Eur J Gastroenterol Hepatol

Breath methane positivity is more common and higher in patients with objectively proven delayed transit constipation

Eur J Gastroenterol Hepatol

Original article
Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis