Digestive Diseases and Sciences

, Volume 59, Issue 3, pp 645–652

Small Intestinal Bacterial Overgrowth in Gastroparesis

Authors

  • Nina S. George
    • Department of MedicineTemple University School of Medicine
  • Abhinav Sankineni
    • Department of Medicine, Section of GastroenterologyTemple University School of Medicine
    • Department of Medicine, Section of GastroenterologyTemple University School of Medicine
Original Article

DOI: 10.1007/s10620-012-2426-7

Cite this article as:
George, N.S., Sankineni, A. & Parkman, H.P. Dig Dis Sci (2014) 59: 645. doi:10.1007/s10620-012-2426-7

Abstract

Objective

To determine symptoms of small intestinal bacterial overgrowth (SIBO) in gastroparesis patients.

Methods

Patients undergoing LBT (lactulose breath test) for evaluation of SIBO were included. LBT was considered positive on the basis of three conventional criteria: (1) hydrogen level increase >20 ppm above baseline by 90 min (H2@90min); (2) dual hydrogen peaks (>10 ppm increase over baseline before second peak >20 ppm (DPHBT); and (3) breath methane increase of >20 ppm above baseline by 90 min. Results of gastric emptying scintigraphy (GES) were recorded. Patients completed the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index.

Results

Of 740 patients who underwent LBT from December 2009 to August 2011, 471 underwent GES, with 201 having delayed GES. Of patients with delayed GES who underwent LBT 87 % were female, 23 % diabetic, 49 % used gastric acid suppressants, 29 % used opiate analgesics, 35 % used pro-motility medications, and 27 % had a history of gastrointestinal surgery. Overall, 79 (39 %) patients with gastroparesis had evidence of SIBO by LBT: 30 (15 %) had positive H2@90min, 53 (26 %) positive DPHBT, and 6 (3 %) positive breath methane test. In gastroparesis patients with positive H2@90min, there was increased severity of bloating (3.80 ± 0.20 vs 3.29 ± 0.12; P = 0.02), early satiety (3.57 ± 0.27 vs 3.05 ± 0.13; P = 0.045), and postprandial fullness (4.20 ± 0.18 vs 3.52 ± 0.12; P < 0.01) compared with negative H2@90min patients. No significant difference in symptom severity was seen between positive and negative DPHBT gastroparesis patients.

Conclusion

In our cohort, 39 % of gastroparesis patients tested positive for SIBO by LBT. Positive H2@90min testing by LBT was associated with increased symptoms of bloating and excessive fullness during and after meals.

Keywords

Small intestinal bacterial overgrowthGastroparesisAbdominal painBloatingLactulose breath test

Abbreviations

SIBO

Small intestinal bacterial overgrowth

LBT

Lactulose breath test

H2@90min

Hydrogen breath testing criteria over 90 min

DPHBT

Double peak hydrogen breath testing

GES

Gastric emptying scintigraphy

GCSI

Gastroparesis Cardinal Symptom Index

PAGI-SYM

Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index

Introduction

Gastroparesis is a condition characterized by symptoms of early satiety, postprandial fullness, nausea, vomiting, and bloating and with evidence of delayed gastric emptying in the absence of mechanical obstruction. Etiologies associated with gastroparesis include diabetes, idiopathic gastroparesis, and post-gastric surgical procedures [1].

Symptoms of gastroparesis do not correlate well with severity of delay on gastric emptying scintigraphy (GES), suggesting other factors contribute to the symptoms [2]. Small intestinal bacterial overgrowth (SIBO) has been identified in up to 60 % of patients with gastroparesis [3]. Symptoms attributable to SIBO include diarrhea, bloating, malnutrition, and weight loss [4]. SIBO is an under-diagnosed disorder, because of the non-specific disease presentation, and symptoms are often attributed as being secondary to an underlying disease that may be causing SIBO [4]. SIBO is associated with a variety of conditions, for example anatomic abnormalities, motor disorders, and achlorhydria of the GI tract. Recent studies have investigated SIBO as an explanation of the symptoms of IBS [5].

SIBO is associated with an increased number of bacteria present in the small bowel, because of either stasis of small bowel content or migration of colonic bacteria into the small bowel. The recommended criterion for diagnosis of SIBO is ≥105 colony-forming units per milliliter of jejunal aspirate [6]. Several difficulties are associated with jejunal aspiration and culture in the diagnosis of SIBO. Breath testing is an indirect test for SIBO based on the metabolic characteristics of bacteria. Several orally administered substrates are used, for example glucose, xylose, and lactulose. Lactulose passes through the small intestine into the large intestine where it is metabolized by colonic bacteria into hydrogen and methane, which are subsequently partially absorbed into the bloodstream and ultimately released in breath. In patients with SIBO, lactulose is metabolized in the small intestine resulting in an early increase in the level of breath hydrogen and/or methane. Lactulose breath testing (LBT) is reported to have sensitivity and specificity of approximately 68 and 44 %, respectively, in detection of SIBO [7].

A variety of definitions are used for positive LBT after lactulose administration, including: breath hydrogen ≥20 ppm above baseline in 90 or 180 min [8, 9], breath methane ≥5 ppm above baseline [5], breath methane ≥20 ppm above baseline [3], dual hydrogen peaks ≥10 ppm above baseline with a decrease of ≥5 ppm from before the second peak [5], and two consecutive hydrogen peaks ≥10 ppm above baseline that is different from the colonic peak defined as being ≥20 ppm above baseline [10].

The purpose of this study was to determine the symptoms and risk factors for SIBO in gastroparesis patients undergoing LBT. We also investigated prevalence, medical history, and symptom association for patients testing positive for different commonly used breath testing definitions for SIBO.

Methods

Patient Population

The initial patient population consisted of patients undergoing LBT for evaluation of SIBO from December 2009 to August 2011 at Temple University Hospital Digestive Disease Center. Radiology reports of gastric emptying scintigraphy were reviewed for each patient, and only patients both with LBT results and delayed GES were included.

Lactulose Breath Testing (LBT)

Patients were instructed to eat a low-carbohydrate meal the day before the test with fasting for at least 12 h before testing. Patients were instructed to not take any antibiotics for four weeks before testing. Smoking and physical exertion were not allowed 1 h before testing or during testing. On the day of the test, patients arrived fasting and were instructed to sit in a chair for the duration of the test. Patients ingested 25 g lactulose in 250 ml water with collection of expired breath samples before lactulose breath testing and then at 15-min intervals for a total of 180 min.

End expiratory breath samples were taken to ensure end aveolar sampling (Quintron gas sampler; Quintron, Milwaukee, WI, USA) with the first 400 mL of the expired breath sample discarded and the subsequent expired gas collected into an air-tight bag. The sample was then analyzed for hydrogen and methane concentrations, in parts per million (ppm), by gas chromatography using a Quintron Breath Tracker [11]. The three criteria used for positive LBT were:

  1. 1

    breath hydrogen level increase >20 ppm above baseline by 90 min (H2@90min);

     
  2. 2

    dual breath hydrogen peaks >10 ppm increase over baseline with a decrease of >5 ppm before the second peak of >20 ppm above baseline (DPHBT); and

     
  3. 3

    an increase of breath methane >20 ppm over baseline by 90 min.

     

Symptom Questionnaires

Patients completed a questionnaire regarding demographics, including age, gender, major chief complaint for which LBT was being performed, presence of diabetes, use of medications (gastric acid suppressants, opiate analgesics, pro-motility agents, diabetic medications, antibiotics), surgical history of the GI tract (esophagus, stomach, small intestine, colon), recent lower gastrointestinal study (barium enema or colonoscopy), and time and content of last meal.

Patients were also asked to complete the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) consisting of 20 symptoms, with symptom severity grading from 0 (none) to 5 (very severe) for symptoms of gastroparesis, functional dyspepsia and gastroesophageal reflux over the last two weeks [12]. The PAGI-SYM questionnaire includes the nine symptoms in the Gastroparesis Cardinal Symptoms Index (GCSI). Additional questions regarding the severity of the symptoms belching, flatus, constipation, diarrhea, and number of bowel movements per week were included.

Several chief complaints were listed on the demographic questionnaire, and patients were instructed to circle the most significant gastrointestinal symptom being evaluated with lactulose breath testing. If several responses were chosen for chief complaints, the authors recorded the symptom with the greatest severity as the chief complaint.

Gastric Emptying Scintigraphy (GES)

Gastric emptying scintigraphy was performed after ingestion of a standard 99m Tc–sulfur colloid radiolabeled liquid egg white (Eggbeaters; Con-Agra Foods, Omaha, NE, USA) sandwich with jam and 300 cc water (225 total calories). Scintigraphy images were obtained 0, 30, 60, 120, 180, and 240 min after meal ingestion. Some patients also had simultaneous liquid gastric emptying with indium-111-labeled water. Gastric emptying was calculated as the percentage retention of the radioactive meal in the stomach over time, by using decay-corrected geometric center of anterior and posterior imaging of gastric counts. Results of gastric emptying scintigraphy were recorded as delayed if there was a delay of solid meal present after either 2 h (>60 % retention) or 4 h (>10 % retention), or 1 h for the liquid meal (>50 % retention) [2].

Data Analysis

Data were expressed as mean ± SEM. Data were analyzed by use of chi-squared tests and independent t tests, with a P value <0.05 used for statistical significance. SPSS v19 was used for data analysis.

Results

Study Population

740 patients underwent LBT during the study period (Table 1). The most frequent symptoms were bloating (25 %), abdominal pain (21 %), and diarrhea (13 %). Most patients were female (80 %), non-diabetic (81 %), without a history of gastrointestinal surgery (77 %), and were not using acid suppressant (56 %), opiate analgesic (75 %), or prokinetic (74 %) agents.
Table 1

Characteristics of patients undergoing LBT

 

All patients undergoing LBT (n = 740)

All patients undergoing LBT and GES (n = 471)

Age (mean ± SEM) years

46.8 ± 0.8

44.7 ± 0.7

BMI (mean ± SEM)

26.0 ± 0.3

25.5 ± 0.3

Gender

 Female

588 (79.5 %)

386 (82.0 %)

Chief complaint

 Diarrhea

97 (13.1 %)

39 (8.3 %)

 Nausea

89 (12.0 %)

75 (15.9 %)

 Bloating

184 (24.9 %)

123 (26.1 %)

 Vomiting

41 (5.5 %)

34 (7.2 %)

 Abdominal pain

157 (21.2 %)

105 (22.3 %)

 Gas

66 (8.9 %)

21 (4.5 %)

 Heartburn

21 (2.8 %)

14 (3.0 %)

 Constipation

54 (7.3 %)

36 (7.6 %)

 Chest pain

6 (0.8 %)

5 (1.1 %)

Use of acid suppressants

328 (44.4 %)

214 (45.5 %)

Use of opiate analgesics

186 (25.3 %)

132 (28.4 %)

Use of pro-motility agents

189 (25.8 %)

155 (33.2 %)

History of diabetes (DM)

138 (18.8 %)

89 (19.1 %)

History of GI surgery

171 (23.4 %)

125 (26.8 %)

Breath tests positive

 H2@90min

150 (20.3 %)

80 (17.0 %)

 DPHBT

176 (23.8 %)

116 (24.6 %)

 CH4@90min

26 (3.5 %)

16 (3.4 %)

 Positive LBT by all three criteria

4 (0.5 %)

3 (0.6 %)

 Positive LBT by at least one criterion

305 (41.2 %)

184 (39.1 %)

LBT, lactulose breath testing; GES, gastric emptying scintigraphy; DM, diabetes; H2@90min, lactulose breath hydrogen testing ≥20 ppm above baseline by 90 min; DPHBT, double peak hydrogen breath test, ≥10 ppm over baseline with decrease of ≥5 ppm before the 2nd peak; CH4@90min, breath methane ≥20 ppm over baseline by 90 min

Of the 471 patients with gastric emptying scans, 201 (43 %) had evidence of delayed gastric emptying (Table 2). Of the 201 patients with delayed gastric emptying, a total of 79 (39 %) met one or more LBT criteria: 30 (15 %) had positive H2@90min, 53 (26 %) were positive for DPHBT, and six (3 %) were positive by breath methane testing. Interestingly, only eight (0.4 %) patients were positive by both H2@90 and DPHBT criteria, one (0.5 %) patient was positive by both H2@90 and CH4@90 criteria, and one (0.5 %) patient was positive by both DPHBT and CH4@90. No patients fulfilled all three criteria.
Table 2

Characteristics of patients undergoing LBT who had GES performed

 

Normal GES undergoing LBT (n = 270)

Delayed GES undergoing LBT (n = 201)

Significance

Age (mean ± SEM) years

44.9 ± 1.0

44.3 ± 1.0

P = 0.64

BMI (mean ± SEM)

25.9 ± 0.4

24.9 ± 0.5

P = 0.11

Gender

 Female

212 (78.5 %)

174 (86.6 %)

χ(1) = 5.05; P = 0.03

Chief complaint

 Diarrhea

24 (8.9 %)

15 (7.5 %)

P = 0.59

 Nausea

40 (14.8 %)

35 (17.4 %)

P = 0.44

 Bloating

69 (25.6 %)

54 (26.9 %)

P = 0.73

 Vomiting

22 (7.8 %)

13 (6.5 %)

P = 0.50

 Abdominal pain

65 (24.1 %)

40 (19.9 %)

P = 0.29

 Gas

15 (5.6 %)

6 (3.0 %)

P = 0.18

 Heartburn

7 (2.6 %)

7 (3.5 %)

P = 0.57

 Constipation

18 (6.7)

18 (9.0 %)

P = 0.35

 Chest pain

1 (0.4 %)

4 (2.0 %)

P = 0.09

Use of acid suppressants

116 (43.1 %)

98 (48.8 %)

χ(1) = 1.47; P = 0.23

Use of opiate analgesics

74 (27.9 %)

58 (29.0 %)

χ(1) = 2.67; P = 0.45

Use of pro-motility agents

85 (31.5 %)

69 (35.0 %)

χ(1) = 1.34; P = 0.51

History of diabetes (DM)

44 (16.3 %)

45 (22.6 %)

χ(1) = 2.78; P = 1.00

History of GI surgery

72 (27.0 %)

53 (26.6 %)

χ(1) = 0.01; P = 0.94

Breath tests positive

 H2@90min

50 (18.5 %)

30 (14.9 %)

χ(1) = 1.02; P = 0.31

 DPHBT

63 (23.2 %)

53 (26.4 %)

χ(1) = 0.61; P = 0.44

 CH4@90min

10 (3.7 %)

6 (3.0 %)

χ(1) = 0.18; P = 0.68

 Positive LBT by all 3 criteria

3 (1.1 %)

0 (0 %)

χ(1) = 2.25; P = 0.13

 Positive by any one criteria

105 (38.9 %)

79 (39.3 %)

χ(1) = 1.10; P = 0.93

LBT, lactulose breath testing; GES, gastric emptying scintigraphy; DM, diabetes; H2@90min, lactulose breath hydrogen testing ≥20 ppm above baseline by 90 min; DPHBT, double peak hydrogen breath test, ≥10 ppm over baseline with decrease of ≥5 ppm before the 2nd peak; CH4@90min, breath methane ≥20 ppm over baseline by 90 min

Mean age of patients undergoing LBT with gastroparesis was 44.3 ± 1.0 years. BMI was 24.9 ± 0.5. Eighty-seven percent were female. Twenty-three were diabetic, with 74 % having insulin dependence. Forty-nine percent used gastric acid suppressants, 29 % used opiate analgesics for pain, 35 % used pro-motility medications, and 27 % had a history of gastrointestinal surgery (Table 2). Major chief complaints in this population were of bloating (27 %), abdominal pain (20 %), nausea (17 %), constipation (9 %), and diarrhea (8 %). Patients with delayed GES compared with patients with negative GES undergoing LBT were predominantly female (χ(1) = 5.04; P = 0.03), without significant association with age (P = 0.64), BMI (P = 0.11), history of diabetes (χ(1) = 2.78; P = 1.0), gastrointestinal surgery (χ(1) = 0.01; P = 0.94), or use of gastric acid suppressants (χ(1) = 1.48; P = 0.23), opiate analgesics (χ(1) = 2.67; P = 0.45), or pro-motility agents (χ(1) = 1.34; P = 0.51) (Table 2).

Hydrogen Breath Test at 90 Min (H2@90min)

Of the 201 patients with delayed gastric emptying, 30 (15 %) had positive H2@90min (breath hydrogen level increase >20 ppm above baseline by 90 min). The chief complaints of these patients were nausea (27 %), abdominal pain (20 %), bloating (13 %), diarrhea (13 %), and constipation (13 %) (Table 3).
Table 3

Characteristics of gastroparesis patients with positive and negative H2@90min and DPHBT test results

 

H2@90min testing in patients with delayed GES

DPHBT testing in patients with delayed GES

Positive breath test (n = 30)

Negative breath test (n = 171)

Significance

Positive breath test (n = 53)

Negative breath test n = 148

Significance

Age (mean ± SEM)

42.4 ± 3.0

44.6 ± 1.1

0.26

45.0 ± 2.0

44.0 ± 1.2

0.82

BMI (mean ± SEM)

23.2 ± 0.7

25.2 ± 0.6

<0.01

24.9 ± 0.9

24.9 ± 0.6

0.60

Gender

 Female

26 (86.7 %)

148 (86.5 %)

χ(1) = 0.0; P = 0.99

45 (84.9 %)

129 (87.2 %)

χ(1) = 0.17; P = 0.68

Chief complaint

 Diarrhea

4 (13.3 %)

11 (6.4 %)

χ(1) = 1.76; P = 0.19

7 (13.2 %)

8 (5.4 %)

χ(1) = 3.44; P = 0.06

 Nausea

8 (26.7 %)

27 (13.8 %)

χ(1) = 2.10; P = 0.15

6 (11.3 %)

29 (19.6 %)

χ(1) = 1.86; P = 0.17

 Bloating

4 (13.3 %)

50 (29.2 %)

χ(1) = 3.23; P = 0.07

21 (39.6 %)

33 (22.3 %)

χ(1) = 5.96; P = 0.02

 Vomiting

0 (0.0 %)

13 (7.6 %)

χ(1) = 2.44; P = 0.12

4 (7.5 %)

9 (6.1 %)

χ(1) = 0.14; P = 0.71

 Abdominal pain

6 (20.0 %)

34 (19.9 %)

χ(1) = 0.00; P = 0.99

7 (13.2 %)

33 (22.3 %)

χ(1) = 2.02; P = 0.16

 Gas

1 (3.3 %)

5 (2.9 %)

χ(1) = 0.02; P = 0.90

0 (0 %)

6 (4.1 %)

χ(1) = 2.22; P = 0.14

 Heartburn

2 (6.7 %)

5 (2.9 %)

χ(1) = 1.06; P = 0.30

2 (3.8 %)

5 (3.4 %)

χ(1) = 0.02; P = 0.89

 Constipation

4 (13.3 %)

14 (8.2 %)

χ(1) = 0.83; P = 0.36

5 (7.5 %)

14 (9.5 %)

χ(1) = 0.18; P = 0.68

 Chest pain

1 (3.3 %)

3 (1.8 %)

χ(1) = 0.33; P = 0.57

0 (0 %)

4 (2.7 %)

χ(1) = 1.46; P = 2.23

Use of acid suppressants

12 (40.0 %)

86 (50.3 %)

χ(1) = 1.08; P = 0.30

30 (56.6 %)

68 (45.9 %)

χ(1) = 1.77; P = 0.18

Use of opiate analgesics

6 (20.0 %)

53 (30.6 %)

χ(1) = 1.56; P = 0.67

10 (18.9 %)

47 (32.0 %)

χ(1) = 5.97; P = 0.11

Use of pro-motility agents

11 (36.9 %)

58 (34.5 %)

χ(1) = 0.13; P = 0.72

21 (40.4 %)

48 (33.1 %)

χ(1) = 0.89; P = 0.34

History of diabetes (DM)

5 (17.2 %)

42 (23.5 %)

χ(1) = 0.56; P = 0.45

11 (21.2 %)

34 (23.1 %)

χ(1) = 0.09; P = 0.77

History of GI surgery

4 (13.3 %)

49 (29.0 %)

χ(1) = 3.20; P = 0.07

14 (27.5 %)

39 (26.4 %)

χ(1) = 0.02; P = 0.88

H2@90min, lactulose breath hydrogen testing ≥20 ppm above baseline by 90 min; DPHBT, double peak hydrogen breath test, ≥10 ppm over baseline with a decrease of ≥5 ppm before the 2nd peak

Patients with positive H2@90min were usually female (87 %), with average age 42.4 ± 3.0 years, and BMI 23.2 ± 0.7. Seventeen percent were diabetic, 13 % had a history of gastrointestinal surgery, and 40 % used acid suppressants, 20 % opiate analgesics, and 37 % prokinetic agents. There was no significant difference between these demographic factors for patients with positive and negative breath H2@90 test (Table 3).

Patients testing positive by H2@90 had increased symptom severity of bloating (3.80 ± 0.20 vs 3.29 ± 0.12; P = 0.02), early satiety (3.57 ± 0.27 vs 3.05 ± 0.13; P = 0.045), and postprandial fullness (4.20 ± 0.18 vs 3.52 ± 0.12; P < 0.01) (Table 4).
Table 4

Symptoms of gastroparesis patients separated by results of LBT

PAGI-SYM Question

H2@90min

DPHBT

Positive breath test (n = 30)

Negative breath test (n = 171)

P value

Positive breath test (n = 53)

Negative breath test (n = 148)

P value

Nausea

3.03 ± 0.35

3.23 ± 0.33

0.32

2.92 ± 0.22

3.29 ± 0.38

0.20

Retching

1.77 ± 0.32

1.38 ± 0.13

0.14

1.51 ± 0.23

1.42 ± 0.14

0.37

Vomiting

1.60 ± 0.35

1.60 ± 0.14

0.50

1.90 ± 0.25

1.50 ± 0.15

0.08

Not able to finish normal sized meal

3.57 ± 0.27

3.05 ± 0.13

0.045

2.85 ± 0.23

3.22 ± 0.14

0.08

Loss of appetite

2.67 ± 0.27

2.58 ± 0.13

0.39

2.41 ± 0.26

2.66 ± 0.13

0.20

Stomach fullness

3.70 ± 0.16

3.57 ± 0.11

0.26

3.57 ± 0.17

3.60 ± 0.11

0.43

Feeling excessively full after meals

4.20 ± 0.18

3.52 ± 0.12

<0.01

3.43 ± 0.20

3.69 ± 0.13

0.14

Bloating

3.80 ± 0.20

3.29 ± 0.12

0.02

3.32 ± 0.22

3.29 ± 0.12

0.40

Stomach/belly visibly larger

3.00 ± 0.29

2.88 ± 0.14

0.35

3.10 ± 0.24

2.82 ± 0.14

0.17

Upper abdominal pain

2.20 ± 0.31

2.77 ± 0.12

0.45

2.67 ± 0.21

2.69 ± 0.14

0.48

Upper abdominal discomfort

2.67 ± 0.32

3.06 ± 0.13

0.13

3.04 ± 0.23

2.99 ± 0.14

0.42

Lower abdominal pain

2.40 ± 0.28

2.44 ± 0.13

0.45

2.36 ± 0.22

2.46 ± 0.14

0.35

Lower abdominal discomfort

2.58 ± 0.26

2.44 ± 0.13

0.38

2.29 ± 0.23

2.51 ± 0.14

0.20

Constipation

3.17 ± 0.34

2.71 ± 0.14

0.11

2.85 ± 0.26

2.75 ± 0.15

0.37

Diarrhea

1.90 ± 0.34

1.93 ± 0.14

0.47

2.06 ± 0.27

1.88 ± 0.15

0.28

Belching, burping

2.73 ± 0.28

2.77 ± 0.13

0.46

2.86 ± 0.21

2.79 ± 0.14

0.33

Flatulence

2.87 ± 0.28

2.60 ± 0.12

0.19

2.83 ± 0.21

2.57 ± 0.13

0.15

LBT, lactulose breath test; H2@90min, lactulose breath hydrogen testing ≥20 ppm above baseline by 90 min; DPHBT, double peak hydrogen breath test, ≥10 ppm over baseline with a decrease of ≥5 ppm before the 2nd peak

Severity of gastric emptying delay was similar between positive and negative H2@90min LBT with severity of retention of radionuclide meal on gastric scintigraphy at 2 h (59.5 ± 2.6 % vs 65.0 ± 1.4 %; P = 0.07) and at 4 h (27.0 ± 3.1 % vs 29.6 ± 1.5 %; P = 0.47).

Double Peak Hydrogen Breath Test (DPHBT)

Fifty three (26 %) of gastroparesis patients that had positive DPHBT test for SIBO (dual hydrogen peaks >10 ppm increase over baseline with a decrease of >5 ppm before the second peak of >20 ppm above baseline). The chief complaints of those with positive breath test were bloating (40 %), abdominal pain (13 %), and diarrhea (13 %) (Table 3). Bloating was more frequently a chief complaint in patients with positive DPHBT than those with a negative test.

Patients with positive test were usually female (85 %), with average age 45.0 ± 2.0 years and BMI 24.9 ± 0.9. Twenty-one percent of patients were diabetics, 28 % had a history of gastrointestinal surgery, 57 % used acid suppressants, 19 % used opiate analgesics, and 40 % used pro-motility agents (Table 3). There was no significant difference between these demographic factors for those with positive and negative DPHBT test (Table 3).

Patients with positive DPHBT test tended to have increased symptom severity for stomach appearing visibly larger (3.10 ± 0.24 vs 2.82 ± 0.14; P = 0.17), vomiting (1.90 ± 0.25 vs 1.50 ± 0.15; P = 0.08), and flatulence (2.83 ± 0.21 vs 2.57 ± 0.13; P = 0.15) (Table 4). Symptom severity between positive and negative DPHBT was not statistical significant different.

There was no significant difference between patients who had positive or negative DPHBT LBT in relation to retention of radionuclide meal at 2 h (66.0 ± 1.9 % vs 63.5 ± 1.6 %; P = 0.31) and 4 h (30.5 ± 2.8 % vs 28.7 ± 1.6 %; P = 0.57).

Methane Breath Test (CH4@90min)

Six of the 201 patients with gastroparesis (3 %) tested positive for breath methane using criteria of ≥20 ppm from baseline at 90 min. For these six patients, compared with the 195 patients with negative breath methane test, there was no significant association between PAGI-SYM symptoms and studied risk factors for SIBO.

Discussion

In this cohort of gastroparetic patients, 39 % had a positive lactulose breath test suggesting SIBO; 15 % of patients tested positive for H2@90min, 26 % positive for DPHBT, and 3 % tested positive for breath methane testing. There was no association with age, BMI, use of acid suppressants, opiate analgesics, or pro-motility agents, history of diabetes, or previous gastrointestinal surgery for gastroparetic patients testing positive for H2@90min or DPHBT for SIBO compared to those who did not. Female patients undergoing LBT and gastric emptying tests had increased prevalence of delayed gastric emptying, but not SIBO.

The main chief complaints for patients with positive H2@90min testing were nausea, abdominal pain, bloating, diarrhea, and constipation. Patients having positive LBT by H2@90min definition were associated with increased symptom severity of bloating, early satiety, and postprandial fullness compared with patients with a negative test. The main complaints of patients with positive DPHBT were bloating, abdominal pain, and diarrhea. Bloating was the chief complaint of more patients with positive DPHBT than of those with a negative test. Bloating was the chief complaint of more patients with positive DPHBT than of those with positive H2@90min test. There were no statistically significant symptoms of increased severity in those with positive DPHBT compared with those with a negative test.

In this study, two interpretations of the LBT hydrogen results were used to define SIBO: an increase in H2 over 90 min and a double peak in the H2 values. The double-peak method has reported sensitivity of 31 % and specificity of 86 % for SIBO, compared with jejunal aspiration cultures [13]. Interestingly, the double-peak method, which is historically the classic definition for a positive result for LBT, identified more positive results (26 %) in our cohort of patients with gastroparesis undergoing LBT but was without significant association with increased gastrointestinal symptom severity. The rise in breath H2 over 90 min identified fewer positive patients (15 %) but these patients had more severe symptoms of bloating, early satiety, and postprandial fullness. This suggests that the rise in H2 over 90 min might be a better definition of positive LBT than the double-peak method in evaluation of symptomatic patients. Studies evaluating the correlation with jejunal aspirations and response of symptoms to treatment of SIBO will further corroborate this.

SIBO in gastroparesis has been evaluated in a previous smaller study that evaluated 50 gastroparesis patients with glucose breath testing (GBT) [3]. Orally ingested glucose is normally absorbed in the proximal small bowel. A rise in breath hydrogen suggests metabolism of the glucose by small intestinal bacteria. The criteria for positive GBT for SIBO in this prior study included:

  1. 1

    breath H2 or methane >15 ppm over baseline;

     
  2. 2

    if baseline H2 or CH4 was <10 ppm, a rise of >20 ppm during the test was considered positive; and

     
  3. 3

    doubling of baseline hydrogen or methane at anytime during the test.

     

The study found that 60 % (30/50) of patients with gastroparesis had a positive GBT by hydrogen breath test; 63 % (19/30) were positive by hydrogen breath test, 27 % (8/30) by methane, and 10 % (3/30) for either breath test criteria. Only longer duration of gastroparesis symptoms was associated with increased prevalence of SIBO in this study [3]. Of note, this study preselected gastroparesis patients with predominance of abdominal pain and bloating symptoms.

SIBO is associated with anatomic and motility disorders of the small intestine. Etiologies of impaired small intestinal motility that might predispose to SIBO may overlap with those of gastroparesis, possibly promoting bacterial overgrowth in the small intestine of gastroparesis patients. Studies evaluating stomach and intestinal motility in diabetic gastroparesis revealed reduction in postprandial gastric motility, reduced amplitude of intestinal motor activity, and absence of the interdigestive motor complexes in the fasting phase [14, 15]. These small intestinal motility abnormalities present in patients with gastroparesis might prevent the cleansing action of propulsive motor activity. Another explanation for SIBO in gastroparesis patients might be the common coincidental use of acid suppressant agents and narcotic analgesics, which may be risk factors for SIBO.

This study was performed in a tertiary motility center on patients undergoing both LBT and gastric emptying scintigraphy for clinical evaluation of their symptoms. This patient population primarily consisted of patients with ongoing symptoms and lack of previous treatment responses. Most patients in this study had GES performed several days within the LBT study. Normative values for lactulose breath testing criteria in patients without gastric emptying were used. Use of normative LBT criteria for “normal” patients with known delayed gastric emptying may control for transit time variations, enabling better evaluation of bacterial overgrowth in this population. Other potential factors that may have had an effect on the result of positive LBT in patients with gastroparesis were opiate analgesic use, history of diabetes, and severity of delay of gastric emptying.

We did not assess the treatment outcome for SIBO to determine if treatment of SIBO improves symptoms. This would be helpful to ascertain if bloating and fullness in gastroparesis patients with positive LBT improves with treatment of SIBO. In our study the number of patients positive for abnormal methane production was low (3 %)—lower than that reported by Reddymasu et al. using glucose hydrogen breath testing [3].

In conclusion, this study found that 39 % of patients with gastroparesis had SIBO, as reflected by positive hydrogen and methane breath test using lactulose and use of any of three LBT criteria. Gastroparesis symptoms of bloating, early satiety, and postprandial fullness were more severe in patients with positive lactulose breath test, specifically breath hydrogen levels ≥20 ppm by 90 min. Different LBT criteria, i.e. abnormal early rise or double peaks, yielded a different number of diagnoses of SIBO and different symptom associations. Importantly, this study suggests that bloating, early satiety, and postprandial fullness may be symptoms of SIBO in some patients with gastroparesis. Further studies should assess which specific symptoms improve with treatment of SIBO in gastroparetic patients.

Conflict of interest

None.

Copyright information

© Springer Science+Business Media New York 2012