Introduction

Glucose (GBT) and lactulose (LBT) breath tests have been recommended by international consensus for the indirect diagnosis of small intestinal bacterial overgrowth (SIBO) and the newly introduced intestinal methanogen overgrowth (IMO), based on the variations of respectively hydrogen and methane concentrations in breath avec ingestion of the above-mentioned sugars. UEG consensus has recommended preferring glucose, due to the difficulty to differentiate, with lactulose as substrate, between rapid intestinal transit and true SIBO (1,2).

Aims & Methods

The aims of this retrospective study were to compare the positivity of GBT and LBT in a population of well-characterized patients with IBS. Among 995 glucose (75 grs) or lactulose (10 grs) breath tests performed in our unit between January 2021 and January 2023, wev extracted a cohort of 287 patients with typical IBS according to Rome IV criteria, after exclusion of patients with a past history of digestive surgery (except appendectomy and cholecystectomy), diabetes, neurological diseases, active or in remission IBD, scleroderma and other connective tissue disorders, chronic intestinal pseudo-obstruction, cirrhosis.
Breath tests were performed after a 8 hour fast, and a strict no fiber and fermentable food the day before. GBT or LBT were performed according to the physician request. During the test, patients filled in a standardized questionnaire to evaluate digestive symptoms, anxiety and depression, and food intake disorders. Various cutoffs for the positivy of the tests were used, according to recommendations: + 12 ppm or +20 ppm for hydrogen variations over baseline (SIBO), and values greater than 10ppm for methane (IMO). For LBT, values were considered only between baseline and 90 minutes after sugar ingestion, to limit false positive results in relation with colonic fermentation of lactulose (120 minutes for GBT) (3).

Results

155 GBT and 132 LBT were performed in IBS patients (71% women, mean age 45, mean BMI: 22.6 kg/m² ). There was no difference between both groups in terms of demographics, IBS type, severity of symptoms, anxiety and depression. Results were clearly different for the positivity of tests: LBT was 10 times more frequently positive than GBT with the +20 ppm cut-off for hydrogen. There was no difference for the positivity of both tests for methane (table 1).

Table 1.

Conclusion

GBT and LBT are not comparable for the diagnosis of SIBO, in a population of well-characterized IBS patients, without comorbidities The very high prevalence of positive LBT (around 50% of IBS patients would be considered SIBO positive) does not make this test acceptable for this diagnosis. Furthermore, the positivity of both tests for SIBO were not correlated with symptoms, which may indicate a poor clinical significance of this diagnosis in IBS. With regards to IMO, both tests give similar results, mainly because baseline values are taken into account: the prevalence of IMO according to these tests is also rather high, and inversely correlated with diarrhea. The significance of the association between IMO and IBS should be tested in prospective interventional studies.

References

1. Pimentel et al. ACG clinical guideline: small intestinal bacterial overgrowth. Am J Gastro 2020; 115-165-78
2. Hammer et al. European guidelines on indications, performance, and clinical impact of hydrogen and methane breath tests in adults and paediatric patients.
UEG Journal 2021.1-26
3. Shaker et al. Pattern of methane levels with lactulose breath testing; can we shorten the test duration? JGH Open 2021; 5: 809-812.

Disclosure

Nothing to disclose

Introduction

The lactulose breath test (L-BT) is a non-invasive method to assess small intestinal bacterial overgrowth (SIBO). However, diagnostic criteria for intestinal methanogenic overgrowth (IMO) differ among experts, and international guidelines lack a definition. Methanogenic flora is linked to slower gut transit in irritable bowel syndrome (IBS), but the effects of methane-targeting treatments on methanogens, colonic transit, and stool form remain unclear.

Aims & Methods

To examine relationships between methanogenesis, constipation, pain and bloating in healthy volunteers and patients with and without IBS. METHODS: Cross-sectional study on adults with L-BT between 2016–2024 at a single center. Each patient completed a Rome IV questionnaire, sociodemographic and medical data and Bristol stool scale. IMO was diagnosed if there were more than 3 measurements of CH₄ over 10 ppm over 180 minutes. We examineded 3 alternate diagnostic thresholds: (A) 10 ppm at any time (American criteria or C1); (B) 10 ppm over baseline before 90 minutes (C2); and (C) 10 ppm over baseline before 60 minutes (C3), We considered “high producers” of CH₄ those that had 2 measurements over 60 ppm. Statistical analysis with Mann-Whitney and Kruskal Wallis test.

Results

We included 5,053 subjects who underwent L-BT (mean age 49 years, 81% women). Of these, 10% were exclusive H2 producers, 2% CH4 producers, and 2.7% were non H2/CH4 producers. CH4 producers had a higher frequency of constipation (p<0.001) and greater total CH4 production in the Bristol 1-2 group. CH4 production over 180 minutes was lower in IBS-D patients, though the overall methane production rate was similar to healthy volunteers. Based on diagnostic thresholds, 92.6% of constipated patients met C1, 52.3% C2, and 18.1% C3, with significant differences (p=0.001). Stricter IMO criteria were associated with greater bloating and pain intensity.

Conclusion

The high proportion of methane production in our asymptomatic controls, compared to previous series, may reflect demographic differences. Methane producers had a higher frequency of constipation. The IMO diagnosis rate varied depending on the criteria used, with stricter criteria identifying patients with more frequent constipation, bloating, and abdominal pain.

Disclosure

None

Introduction

Colorectal cancer (CRC) screening has been widely implemented, and recent advances in fecal immunochemical testing (FIT) have led to a shift in screening modalities from guaiac fecal occult blood testing (gFOBT) to FIT. In Japan, FIT was introduced into the national screening program in 1992, and a two-sample method has been offered to individuals aged 40 years and older. However, there is no standardized use of testing devices or cutoff values. Although hemoglobin concentrations of 100-150 ng/g are commonly used, few studies have evaluated cut-off values in population-based screening. An optimal cut-off value should be defined for adequate quality assurance by considering the benefits and harms of CRC screening.

Aims & Methods

To evaluate the optimal cutoff value for population-based screening, we compared the test performance of FIT according to different cutoff values. A total of 383,793 individuals participated in population-based screening in Ibaraki Prefecture from April 2021 to March 2023. The OC-sensor was used as the testing modality, with a default cut-off value of 100 ng/g. Test performance indicators, including positive rate, detection rate, positive predictive value (PPV), cancer miss rate, and number needed to scope (NNS), were assessed across cut-off values ranging from 100 to 250 ng/g. Detection rate, PPV, and NNS were explicitly calculated for CRC/ Advanced neoplasia (AN). Since the colonoscopy completion rate is typically around 70％, PPV and NNS were calculated on a per-protocol basis.

Results

Subjects who submitted two samples were 370419. Among them, 863 cases of CRC and 1944 cases of advanced adenomas were diagnosed. At a cutoff value of 100 ng/g at the baseline, the positive rate was 6.7% (95%CI: 6.7-6.8) and the colonoscopy completion rate was 76.0% (95%CI: 75.4-76.5) (Table). For AN, the detection rate was 0.76％ (95%CI: 0.73-0.79), 14.8% for PPV (95%CI: 14.3-15.3), and 6.8% (95%CI: 6.5-7.0) for NNS. For CRC detection, the detection rate was 0.23％ (95%CI: 0.22-0.25), 4.5% for PPV (95%CI: 4.3-4.8), and 22.0% (95%CI: 22.0-23.5) for NNS. The NNS decreased as the cutoff value increased, but the CRC miss rate also increased. The cutoff value reached 180 ng/g, the CRC miss rate became 19.5% (95%CI:16.8-22.1), whereas the positive rate was 4.2% (95%CI: 4.2-4.3), 0.19％ (95%CI: 0.17-0.20) for CRC detection rate, 5.9% (95%CI: 5.5-6.3) for PPV, and 16.9 (95%CI: 15.8-18.2) for NNS.

Conclusion

The current cutoff value led to high detection rates for both CRC and AN, but it also required a greater number of colonoscopies. The availability of colonoscopy services varies across local municipalities and is often insufficient in rural areas. Adjusting the cutoff value is frequently used to address disparity in access to colonoscopy. However, the trade-off among benefits, harms, and resources is influenced by the social context, including individual preference and value. Therefore, an acceptable level of cancer miss rates should be carefully evaluated. Since the optimal cutoff value cannot be determined unequivocally, a comprehensive decision should be made by balancing benefits, harms, and resources, while also considering the preference of local residents.

References

Young GP, et al. Detection of advanced colorectal neoplasia and relative colonoscopy workloads using quantitative faecal immunochemical tests: an observational study exploring the effects of simultaneous adjustment of both sample number and test positivity threshold. BMJ Open Gastroenterol. 2020 ;7: e000517

Introduction

Non-invasive biomarkers that enable accurate diagnosis, patient stratification, and therapy monitoring in irritable bowel syndrome (IBS) are still lacking in clinical practice. Volatile organic compounds (VOCs) produced by the host metabolism, inflammatory processes, and the gut microbiota are present in exhaled breath and have recently gained attention as promising biomarker candidates. Prior research (Van Malderen et al. (2020)) demonstrated that breath VOC profiling could accurately distinguish IBS patients from healthy controls using multicapillary column/ion‑mobility spectrometry (MCC/IMS).

Aims & Methods

The present study aimed to assess the potential of high-resolution gas chromatography-quadrupole time‑of‑flight mass spectrometry (GC-QTOF-MS) profiling of breath VOCs to define distinct compound classes that enhance the mechanistic understanding of breath-based biomarkers in IBS. To this end, breath samples from 12 IBS patients and 11 healthy controls were collected, together with matched ambient air samples and were analyzed using GC-QTOF-MS. Breath samples were corrected by background subtraction and least‑absolute‑shrinkage‑and‑selection‑operator (LASSO) regression was applied with leave‑one‑out cross‑validation (LOOCV) to identify discriminative VOC signatures. The feature set was subsequently filtered to exclude sporadically detected VOCs and compounds of exogenous (non-host) origin. Finally, the remaining VOCs were mapped to putative pathways.

Results

IBS patients had a mean ± SD age of 36 ± 15.3 years, compared with 56 ± 15.4 for the healthy controls. The male-to-female ratio was 3:9 in the IBS cohort and 5:6 among the healthy controls. Within the IBS group, 7 patients had diarrhea-predominant IBS, 4 had constipation-predominant IBS, and 1 had mixed-type IBS. The LASSO regression model, validated with LOOCV, demonstrated high discriminative performance in differentiating IBS patients from healthy controls, with the corresponding model metrics in Table 1. Furthermore, the feature selection identified a panel of discriminative VOCs - predominantly alkanes, aldehydes, and ketones - that were up-regulated in the IBS breath profiles. These elevated compound classes could putatively be linked to mechanisms relevant to IBS pathophysiology, including altered microbial metabolism, increased oxidative stress, and low-grade inflammation.

Table 1: Model metrics

Conclusion

Volatomic breath profiling in IBS, shows great potential for discriminating IBS from healthy controls and for defining clinically relevant biomarkers composed of specific VOCs. Nonetheless, the limited sample size might risk model overfitting and introduces uncertainty in the estimates. Further research including larger, confounder-controlled cohorts is necessary, along with the targeted validation of the identified VOCs to further confirm their mechanistic role in IBS.

References

Van Malderen K, Hanning N, Lambrechts H, Haverhals T, Van Marcke S, Ceuleers H, De Man JG, De Winter BY, Lamote K, De Schepper HU. Volatile organic compound profiling as a potential biomarker in irritable bowel syndrome: A feasibility study. Front Med (Lausanne). 2022 Aug 4;9:960000. doi: 10.3389/fmed.2022.960000. PMID: 35991639; PMCID: PMC9388331.

Introduction

Intestinal methanogen overgrowth (IMO) is characterized by colonization of methanogenic species in the gastrointestinal tract and elevated breath methane levels, which are associated with constipation. It can be diagnosed with a simple, non-invasive hydrogen and methane breath test (HMBT). We wanted to determine if IMO is associated with any other symptoms, medications or medical conditions.

Aims & Methods

A large questionnaire-based study was conducted in over 1000 patients of which 731 patients underwent a lactulose HMBT. The 26-item questionnaire included questions about medical history and symptoms, and we used this to identify positive predictors for IMO. Patients were considered positive for IMO if any of the breath samples provided had a concentration of ≥10 ppm methane. Samples were analysed using gas chromatography and statistical significance of associations and predictors were calculated using chi square and logistic regression, respectively.

Results

232 patients were positive for IMO on HMBT. There was a positive association for constipation (P < 0.001) and negative association for diarrhoea (P = 0.002). Excessive methane was associated with stools that appear fatty/greasy and/or tend float (P < 0.001) where 75% of patients with IMO reported this. 22 patients in this cohort had inflammatory bowel disease (IBD) of which 91% tested negative for methane (P = 0.020).

Conclusion

This large questionnaire study has provided further evidence that excessive breath methane production is associated with constipation and inversely associated with diarrhoea and IBD. We have also shown that excess methane may also lead to fatty/greasy stools that can float. HMBT plays an important role to identify IMO in patients with constipation.

Introduction

Intestinal microbiota are prominent in the etiology of irritable bowel syndrome (IBS). In this exploratory study, we investigated short- and long-term changes in the microbiota of IBS patients after intervening with a low-FODMAP diet (LFD) or probiotics (an 8 strains lactobacilla) using a standardized microbiota characterization test intended for routine use.

Aims & Methods

We analyzed data and fecal samples collected in a previous trial from non-comorbid IBS patients before treatment, and then again after four weeks and one year of treatment. Response to treatment was defined by a reduction in the IBS-SSS score, and the gut microbiota were characterized using the standardized and GA-map® Dysbiosis Test Lx.

Results

Of the 25 responders to either treatment, two of the 22 with fecal samples available were dysbiotic at baseline, increasing to eight out of 19 after four weeks; after one year all responders providing a sample were normobiotic (n=15). After four weeks, the abundance of Bacilli, Lactobacillus spp. and Streptococcus salivarius ssp. thermophilus were temporarily increased in the probiotic responder group (p<0.05), while for LFD responders Anaerobutyricum hallii had decreased. There was a greater abundance of R. gnavus at baseline in those responding to probiotics than in those responding to LFD.

Conclusion

In addition to improving IBS symptoms, sustained LFD or repeat probiotics tended to temporarily alter the microbiota profile in responders. Microbiota characterization is a promising tool for monitoring IBS treatments; however, more extensive studies are needed.

Disclosure

Marwah Al-sheikh, Dorit Vedel Ankersen and Mette Bennedsen declare no conflict of interest
Christina Casén is an employee of Genetic Analysis AS and owns stocks and shares in Genetic Analysis AS.
Kristin Gravdal and Graceline Tina Kirubakaran are employees of Genetic Analysis AS.
Johan Burisch reports personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.
Pia Munkholm has received consulting or lecture fees from AbbVie, Calpro A/S, Ferring Pharmaceuticals, Jansen-Cilag, Celgene, Takeda, Tillotts Pharma, Merck Sharp & Dohme, Pfizer, and research funds from Coloplast, Ferring Pharmaceuticals, Jansen-Cilag, Merck Sharp and Dohme, Pharmaforce, Svar A/S, Takeda, Tillotts Pharma, Novo Nordic.