The prevalence of overweight and obese individuals is increasing worldwide. A recent study demonstrated that, worldwide through 2013, the prevalence of adults with a body mass index of 25 kg/m2 or greater had risen to include 36.9% of men and 38.0% of women [
Roux-en-Y gastric bypass (RYGB) has been the gold standard bariatric procedure, with 60–70% excess weight lost at two years, as well as significant improvement in glycemic control in diabetic patients [
In patients after RYBG, quantitative bacteriology has revealed elevated populations of bacteria in both the gastric pouch and the bypassed stomach [
After an overnight fast, measurements of breath hydrogen and methane before and after intake of oral glucose are both a safe and inexpensive test compared to quantitative bacteriology. The glucose-hydrogen breath test has a reported sensitivity of 44% to 90% and specificity of 78% to 83% compared to quantitative bacteriology for identifying colonic-type bacteria performed on aspirates from the small intestine [
Several studies have validated the role of the glucose-hydrogen breath test in identification of small intestinal glucose malabsorption. The pathophysiology of the neonatal diarrheal illness glucose-galactose malabsorption has been shown to involve a defect in the intestinal brush border Na+/glucose cotransporter (SGLT1) [
In studies of patients who have undergone RYGB, an early study from 1981 revealed abnormal breath hydrogen levels after glucose ingestion in six of eight patients (75%) after RYGB [
Based upon these prior studies, the hypothesis of this present study is that breath testing before and after intake of oral glucose is effective for the identification of evidence of glucose malabsorption in individuals with abdominal symptoms after RYGB.
This human study was approved by the Human Studies Subcommittee of MedStar Research Institute (Hyattsville, MD) on December 10, 2013. This is a retrospective study of patients who underwent Roux-en-Y gastric bypass surgery (see Figure
Roux-en-Y gastric bypass surgery. The orientation of the gastrojejunal anastomosis may be retrocolic or antecolic. In our experience, a retrocolic approach is more common after an open surgical procedure, while an antecolic approach is more common after a laparoscopic approach to surgery. The bypassed stomach and the loop of small intestine (termed the biliopancreatic limb) distal to the pylorus but proximal to the jejunojejunal anastomosis may function as a blind pouch.
We have previously described performance of glucose-hydrogen/methane breath testing in individuals with thiamine deficiency after RYGB [
Statistical analysis was performed using a standardized computer program (StatView; SAS Institute Inc., Cary, NC). The potential association between glucose malabsorption (late rise) and SIBO (early rise) was evaluated using Fisher’s exact test. A
The average age of these subjects was 49 (range: 28 to 71) years old. This was a female predominant (95%) study. The average (±SEM) body mass index at the time of glucose breath testing was 35 ± 10 kg/m2 with a range of 21 to 54 kg/m2. The majority of subjects were Black Americans (70%), followed by Caucasian Americans (30%). Of the 63 individuals who had undergone RYGB, 21 subjects (33%) had been previously diagnosed with diabetes mellitus. The time period between RYGB and glucose-hydrogen breath testing averaged (±SEM) 65 ± 5 months. The baseline demographics for these study subjects are summarized in Table
Demographics of individuals after Roux-en-Y gastric bypass surgery undergoing glucose-hydrogen breath testing (
Age | |
Mean | 49 years |
Range | 28–71 years |
Gender | |
Female | 60 (95%) |
Male | 3 (5%) |
Race | |
Black Americans | 44 (70%) |
Caucasians | 19 (30%) |
Body mass index | |
Mean ± SEM | 35 ± 10 kg/m2 |
Range | 21 to 54 kg/m2 |
Months between bariatric | |
surgery and breath testing | |
Mean ± SEM | 65 ± 5 months |
Range | 6 to 228 months |
After receiving oral glucose, subjects could demonstrate a rise in breath hydrogen or methane of at least 10 parts per million at ≤30 minutes (consistent with upper gut bacterial overgrowth) or at least 10 parts per million above the plateau breath level measured prior to collection of breath at ≥45 minutes, as shown in the representative breath test in Figure
Number of individuals after Roux-en-Y gastric bypass surgery with an early rise of breath hydrogen or methane (SIBO
Early rise in breath ( |
|||
---|---|---|---|
No | Yes | ||
Late rise in breath | No | 12 | 0 |
( |
Yes | 5 | 46 |
Representative subject in whom breath levels of hydrogen (closed circles) and methane (open circles) were measured; 25 grams of oral glucose was given after collection of breath at time 0. Note the initial rise in breath hydrogen (early rise), with a second rise in breath hydrogen (late rise) beginning at 80 minutes.
As an apparent result of the process of conversion of the patients’ medical records from paper charts to an electronic medical record, among the 63 individuals who had undergone RYGB, preoperative and 3-year postoperative weights were available in only 33 of these individuals. In the 33 individuals, 26 subjects were noted on glucose breath testing to have a late rise in breath hydrogen or methane (supporting the presence of glucose malabsorption), while 7 individuals had no late rise. In the 26 individuals with evidence for glucose malabsorption, the average percentage (±SEM) of excess body weight lost at 3 years was 66% (±3.8). In the 7 subjects with no findings supporting glucose malabsorption, the average percentage (±SEM) of excess body weight lost at 3 years was 56% (±8.1). With this limited information, there was no increase in the percentage of excess weight loss in subjects with evidence for glucose malabsorption (unpaired
Among patients with abdominal symptoms after RYGB, 81% had evidence for malabsorption by breath testing performed before and after receiving oral glucose. These findings support our hypothesis that glucose-hydrogen breath testing can function as a safe and inexpensive test for the examination of patients with abdominal symptoms after RYGB. Further clinical studies are underway to determine whether an abnormal hydrogen breath test after RYGB improves treatment outcomes in individuals with postoperative abdominal symptoms.
In our original study of upper gut bacterial overgrowth in individuals with thiamine deficiency after RYGB, we used a 50-gram dose of glucose [
Studies have however shown that, in individuals with a rapid oral-cecal transit of <75 minutes, the glucose breath test may not be of benefit due to false positive results [
Among 63 individuals after RYGB, the frequent finding (81%) of a late rise (≥45 minutes) in breath hydrogen or methane supports the presence of glucose malabsorption. We however cannot determine the percentage of glucose malabsorption by the use of glucose breath testing.
Our present findings are supported by similar findings of decreased glucose absorption in the jejunal Roux limb in rats after RYGB [
Stearns et al. [
It has been additionally shown that glucose absorption is lower in obese compared to lean Zucker rats [
Results from studies of glucose transporters and glucose absorption in humans are unclear and suggest variability in the surgical anatomy during performance of RYGB. In a multicenter study from Germany and Switzerland, Ritze and associates reported that, in 20 obese individuals after RYGB, jejunal GLUT2 mRNA expression (relative to 18S) was increased compared to 14 lean individuals as controls [
In a second human study from Australia, Nguyen et al. reported a potential increase in mRNA expression of SGLT1 and GLUT2 in jejunal mucosal biopsies after RYGB in 11 subjects [
The authors [
In a prior study, Nguyen et al. had reported, in 10 individuals who had undergone RYGB, that the transit of glucose to the cecum was only 26
The finding in our present study of a significantly higher prevalence of glucose malabsorption in subjects with upper gut bacterial overgrowth when compared to subjects who did not have upper gut bacterial overgrowth supports bacterial overgrowth as a potential mechanism for the development of glucose malabsorption. This hypothesis is supported by a prior study of small intestinal biopsies which showed that mucosal sodium-dependent glucose transport was reduced in individuals with evidence for bacterial contamination of the small intestine [
Because only a small percentage of individuals in our present study had normal glucose-hydrogen breath testing after RYGB surgery, it is not yet clear whether glucose malabsorption is an origin for calorie malabsorption and thus continued weight loss in morbidly obese individuals after RYGB. This question will require a much larger patient population to determine whether glucose malabsorption improves postoperative weight loss in individuals after bariatric surgery.
There are specific limitations to our present study. This is a retrospective study and so the results may not be generalizable to all patients who have undergone RYGB. Our RYGB patients do not routinely undergo a repeat glucose breath test after antibiotic treatment of bacterial overgrowth. The individuals in this study who underwent glucose breath testing had previously undergone RYGB and were then seen in consultation because of abdominal symptoms. Individuals with no abdominal symptoms following RYGB are not included in this present study. In addition, it is uncertain whether the finding of glucose malabsorption is the result of RYGB or the result of obesity. By performing preoperative and postoperative glucose-hydrogen breath testing on the same morbidly obese subjects and by evaluating the clinical response to oral antibiotic therapy, many of these remaining questions should then be better addressed.
In conclusion, patients with abdominal symptoms after RYGB demonstrate a high prevalence of glucose malabsorption when evaluated by hydrogen breath testing after receiving oral glucose. These findings support glucose-hydrogen breath testing as a safe and inexpensive test for the examination of patients with abdominal symptoms after RYGB. Further clinical studies are underway to determine whether an abnormal hydrogen breath test after RYGB improves treatment outcomes in individuals with postoperative abdominal symptoms.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Hiral Shah and Bikram Bal participated in the coordination of and helped in collection of clinical and experimental data for this study. Iman Andalib completed the statistical analysis for this study and assisted in drafting the paper. Timothy R. Shope, Frederick C. Finelli, and Timothy R. Koch conceived and designed the study, participated in the statistical analysis, completed the paper review, and finalized the paper preparation. All authors read and approved the final paper.