Ready for Prime Time? Breath Testing to Diagnose Intestinal Dysbiosis and Guide Management in Patients With Functional Defecation Disorders

Microbial dysbiosis is characterized by alterations in the diversity, function, and density of intestinal microbes. Clinicians have recognized for many years that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these areas [1]. SIBO has been linked and is highly prevalent in several gastrointestinal and extraintestinal condition [1], particularly in disorders of gut–brain interaction (DGBI). Recent studies have reported increased prevalence of SIBO in irritable bowel syndrome at 35.5% (95% CI 33.6–37.4) [2] and functional dyspepsia at 32.7% (95% CI 21.6–46.1) [3]. Recent guidelines [4] from the American College of Gastroenterology have coined the term “intestinal methanogen overgrowth (IMO)” to emphasize the importance of methane production by methanogens belonging to the domain Archaea, rather than intestinal dysbiosis driven solely by bacteria. IMO has been associated with irritable bowel syndrome-constipation subtype (IBS-C) [5], (odds ratio = 3.51, 95% confidence interval [CI] = 2.00–6.16) and with slower small bowel and colonic transit times [6]. The link between SIBO and DGBI, as well as other gastrointestinal conditions, is controversial due to the lack of reliable diagnostic tests for SIBO. The widely used Lactulose Breath Test (LBT) has very low sensitivity (42.0%) and specificity (70%) [7] for diagnosing SIBO and primarily measures intestinal transit [8]. Although the Glucose Breath Test (GBT) performs slightly better than LBT, it also suffers from low sensitivity (54.5%) and specificity (83.2%) [7]. The current diagnostic “gold” standard small bowel aspirate and culture, is invasive, technically challenging [1, 9], and only detects 20% of microbes that can be cultured using traditional culture methods [10]. Recent studies employing culture-independent methods, such as quantitative polymerase chain reaction (qPCR) to quantify the duodenal mucosal bacterial load [11] and high-throughput sequencing of duodenal aspirates [12], have identified specific microbes associated with SIBO, marking a significant advancement in diagnosis and management of patients with small intestinal dysbiosis. Two large retrospective cohort studies from reputable quaternary gastroenterology departments with high-profile Neurogastroenterology services investigated the role of microbial dysbiosis in evacuation disorders. Soetaert et al. [13] conducted a single-center study, including a large cohort of 488 patients with abdominal bloating who underwent either LBT (n = 144) or GBT (n = 344), along with anorectal physiological testing (high-resolution anorectal manometry (HR-ARM), rectal sensory testing (RST), and balloon expulsion test (BET)). They highlighted the limitations of the diagnostic modalities used for SIBO and IMO and observed significantly higher rates of SIBO and SIBO+IMO when LBT was utilized compared to GBT. Ultimately, this study did not reveal any significant differences in anorectal physiologic parameters between patients who tested positive or negative for SIBO or IMO. The second single-center cohort study by Damianos et al. [14], used a slightly different approach. They identified a cohort of 1073 patients who either underwent small bowel aspirate and culture (n = 436) or breath testing (n = 637) with glucose (n = 334), lactulose (n = 85) or an unspecified substrate, along with anorectal physiological testing. They also included 34 patients who had undergone scintigraphy and were diagnosed with slow transit constipation. An abnormal BET was observed in patients with microbial overgrowth compared to those without SIBO (p = 0.020). Interestingly, they found that there was no association between abnormal BET (a reliable indicator of dyssynergic defecation) and SIBO prevalence rates when using small bowel aspirate and culture. Moreover, IMO was significantly more prevalent in patients with dyssynergic defecation compared to those with slow transit constipation (71.5% vs. 27.4%). These partly contradictory results could have implications for clinical practice, making it important to carefully assess the differences and limitations of these studies before drawing conclusions. While Soetaert et al. [13] investigated patients with bloating, the majority of whom were in the setting of chronic constipation or non-diarrheal IBS, the clinical symptomatology of the patients in the second study [14] was not accounted for. Due to the retrospective study design, neither study considered the impact of proton pump inhibitor use or recent antibiotic use on the results of SIBO/IMO diagnostic tests. Moreover, Damianos et al. [14] acknowledge that the culture results demonstrate a weak and unreliable relationship between and dyssynergic defecation, and likely are unable to diagnose IMO. This is important since culture is currently regarded as the gold standard for SIBO diagnosis. Other studies have linked IMO to constipation [5], but whether it is a cause or a consequence of chronic constipation remains unclear. Patients with dyssynergic defecation, with or without SIBO/IMO, should prioritize pelvic floor rehabilitation through physical therapy and biofeedback. For those suffering from constipation, implementing appropriate evidence-based treatment strategies is essential. These approaches are preferable to prescribing antibiotics for suspected IMO, as they help prevent antibiotic misuse until more reliable diagnostic tests and therapies for IMO and SIBO are established in clinical practice. To establish any meaningful association between SIBO/IMO in gastrointestinal conditions, there is broad recognition of the need for validated diagnostic measures for SIBO and IMO [8]. In the absence of reliable diagnostic tests, treating SIBO with antibiotics relies on a trial-and-error approach and should be avoided. The lack of diagnostic tests for SIBO also complicates the assessment of treatment response and raises uncertainties about relapse and the need for retreatment. We agree with Soetaert et al. [13] about the importance of educating healthcare providers to preventing unnecessary antibiotic exposure, aligning with the principles of antibiotic stewardship. In routine clinical settings, patients frequently present with the expectation for diagnostic tests and treatment. Based on the data, we recommend advising against routine testing for SIBO in patients presenting with bloating and distention unless clear risk factors for SIBO warrant such an approach. The studies by Damianos et al. [14] and Soetaert et al. [13] appear to have contradicting results. One study [14] found a link between microbial overgrowth and evacuation disorders diagnosed by GBT/LBT, while the other large study [13] failed to confirm this association. Another discrepancy in one of the studies is even more striking. While the study [14] found an association between breath test results and dyssynergic defecation, it did not establish a link between the BET, a key diagnostic parameter for dyssynergic defecation, and microbial overgrowth identified by culture. The retrospective design of both studies restricts the ability to draw firm conclusions about the mechanisms and clinical implications of microbial dysbiosis in evacuation disorders. Furthermore, both studies were conducted in tertiary centers, highlighting the potential for selection bias that prospective studies must address to enhance the robustness and generalizability of future findings. The role of IMO as either a cause or a consequence of constipation, as well as its impact on evacuation disorders, remains to be proven. It is evident that prospective studies with interventions targeting intestinal dysbiosis are essential to inform clinical practice. However, in the clinical setting, the lack of reliable diagnostic tests to diagnose microbial dysbiosis poses a barrier that needs to be addressed as a priority. Both authors drafted, reviewed, and approved the final manuscript and contributed equally. The authors have nothing to report. G.H. report to be on the advisory boards of Australian Biotherapeutics, Glutagen, Bayer, and received research support from Bayer, Abbott, Pfizer, Janssen, Takeda, and Allergan. He serves on the Boards of the West Moreton Hospital and Health Service, Queensland, UQ Healthcare, Brisbane, and the Gastro-Liga, Germany. He has a patent for the Brisbane aseptic biopsy device and serves as Editor of the Gastro-Liga Newsletter. He is coauthor for the SIBO section on Up to Date. A.S. is Chief Investigator of a National Health and Medical Research Council (NHMRC) investigator (2026–2030) grant and a coauthor for the SIBO section on Up to Date. This article is linked to Damianos JA and Soetaert C et al. papers. To view this article, visit https://doi.org/10.1111/nmo.70211 and https://doi.org/10.1111/nmo.70205. The authors have nothing to report.