Substrate-dependent Differences of Colonic Hydrogen Production in a Patient With Fructose Malabsorption

Background

Hydrogen (H₂)/methane (CH₄) breath testing (HMBT) is the most widely utilized diagnostic modality for the diagnosis of many common gastrointestinal conditions including small intestinal bacterial overgrowth (SIBO), intestinal methanogen overgrowth (IMO), irritable bowel syndrome-like symptoms, and carbohydrate malabsorption.^1-3 Often, in interpreting the lactulose HMBT, the term “hydrogen nonproducer” is used for a H₂ breath profile that is ”flatline”.^4,5 Here we report on a patient with abnormal fructose HMBT results that failed to produce H₂ upon lactulose, glucose, lactose, and sorbitol HMBT.

Case report

Here we present a 47-year-old male patient with diarrhea, postprandial nausea, meteorism, eructation, abdominal fulness, and loss of appetite for almost 2 years, resulting in an unintentional weight loss of 10 kg. This case report was exempted from ethical clearance by the local Institutional Review Board, and the patient provided written informed consent to publish his case. Upon anamnesis, the patient reported to suffer from histamine intolerance and allergy to pollen and grass and denied any routine medication. Upper gastrointestinal endoscopy, colonoscopy, computed tomography of the abdomen and pelvis, complete blood cell count, kidney/liver/pancreas function tests, C-reactive protein, thyroid stimulating hormone, celiac disease serology, immunoglobulin E (IgE)-mediated food allergy, as well as fecal calprotectin showed normal findings. Moreover, stool culture did not grow the following enteropathogens: Salmonella, Yersinia, Shigella, Vibrio, Campylobacter, and enteropathogenic Escherichia coli. HMBT using fructose, lactose, sorbitol, glucose, and lactulose was then performed to detect carbohydrate malabsorption and/or SIBO/IMO. Finally, the patient could be diagnosed with fructose malabsorption as indicated by elevated H₂ levels during HMBT using 25 g of fructose (Figure A). Self-reported symptoms during this test included nausea, meteorism, and eructation. Interestingly, the patient failed to produce H₂ upon HMBT using 10 g of lactulose (Figure B). Furthermore, all other HMBT (ie, lactose, sorbitol, and glucose) remained negative (data not shown).

Figure.

Graphical representation of the fructose (A) and lactulose (B) hydrogen (H₂)/methane (CH₄) breath test performed with our patient. Gas chromatography was employed using a QuinTron Model DP Plus MicroLyzer (QuinTron, Milwaukee, WI, USA). Baseline breath H₂/CH₄ concentrations were determined after an overnight fasting state of 14 hours. Additionally, pre-test preparation included (1) no antibiotics or bowel preps for 4 weeks, (2) no laxatives, antacids and prokinetics for one week, and (3) a low carbohydrate and dairy diet 2 days before the breath test. After determining baseline breath levels, lactulose and fructose were given in a dose of 10 g and 25 g, respectively, dissolved in 200 mL of water. The end-expiratory breath H₂/CH₄ concentrations were then measured at 15, 30, 45, 60, 90, 120, 150, and 180 minutes after sugar ingestion. H₂ nonproduction on the basis of a H₂ flatline was defined with all values ≤ 10 ppm and the absence of a H₂ peak.⁴ The fructose breath test was considered positive if there was a rise of ≥ 20 ppm H₂ above the baseline concentration within 60-180 minutes (ie, colonic passage).² Furthermore, a breath test was considered positive when there was a CH₄ level of ≥ 10 ppm at any time during the test.¹

Discussion

Lactulose HMBT has been used for the diagnosis of gastrointestinal conditions such as altered microbial fermentation, including SIBO/IMO, maldigestion/malabsorption syndromes, and oro-cecal transit time (OCTT) determinations.^1-4 Here, we present a patient that produced significant amounts of H₂ upon fructose but failed to produce H₂ upon lactulose HMBT. The notion, however, that individuals may be H₂ nonproducers conflicts with previous studies describing the universal inclusion of H₂-producing bacteria belonging to the Bacteroidetes phylum in the human gut.^4,6,7 With this respect, a recent study demonstrated the concurrent production of CH₄ and hydrogen sulfide (H₂S) in patients presenting a flatline pattern upon lactulose HMBT, suggesting that H₂ had been produced as an initial part of the fermentation process, becoming then fully converted to CH₄ and/or H₂S by H₂-consuming bacteria present in the colon.⁴

The breath test findings for the patient reported here are (1) flatline pattern using lactulose, (2) significant colonic H₂ production using fructose, and (3) failure to produce significant amounts of CH₄. In the absence of elevated CH₄ breath levels during HMBT, it seems rather unlikely that H₂-consuming bacteria selectively act on H₂ produced by the fermentation of lactulose but not fructose. An important limitation of this report is the lack of H₂S measurement being a key constraint with respect to the interpretation of lactulose HMBT flatline patterns.

Additionally, while 10 g of lactulose is a widely used standard, this load may be insufficient to elicit a measurable H₂ rise within the sampling window in some patients.

Furthermore, and although H₂ responses are substrate- and dose-dependent by design (ie, absorption/fermentation biology and challenge load can alter gas kinetics and detection timing), this case illustrates that a flatline pattern upon lactulose HMBT does not necessarily preclude H₂ production with other sugars entering the colon due to intestinal malabsorption.