Current and Future Approaches for Diagnosing Small Intestinal Dysbiosis in Patients With Symptoms of Functional Dyspepsia

Abstract

The development and application of next generation sequencing technologies for clinical gastroenterology research has provided evidence that microbial dysbiosis is of relevance for the pathogenesis of gastrointestinal and extra-intestinal diseases. Microbial dysbiosis is characterized as alterations of diversity, function, and density of the intestinal microbes. Emerging evidence suggests that alterations of the gastrointestinal microbiome are important for the pathophysiology of a variety of functional gastrointestinal conditions, e.g., irritable bowel syndrome (IBS) and functional dyspepsia (FD), also known as disorders of brain-gut axis interaction. Clinicians have for many years recognized that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these sites. SIBO presents with symptoms which overlap with symptoms of FD and IBS, point toward the possibility that SIBO is either the cause or the consequence of functional gastrointestinal disorders (FGIDs). More recently, new terms including “intestinal methanogen overgrowth” and “small intestinal fungal overgrowth” have been introduced to emphasize the contribution of methane production by archea and fungi in small intestinal dysbiosis. There is emerging data that targeted antimicrobial treatment of SIBO in patients with FD who simultaneously may or may not have IBS, results in symptom improvement and normalization of positive breath tests. However, the association between SIBO and FGIDs remains controversial, since widely accepted diagnostic tests for SIBO are lacking. Culture of jejunal fluid aspirate has been proposed as the “traditional gold standard” for establishing the diagnosis of SIBO. Utilizing jejunal fluid culture, the results can potentially be affected by cross contamination from oropharyngeal and luminal microbes, and there is controversy regarding the best cut off values for SIBO diagnosis. Thus, it is rarely used in routine clinical settings. These limitations have led to the development of breath tests, which when compared with the “traditional gold standard,” have sub-optimal sensitivity and specificity for SIBO diagnosis. With newer diagnostic approaches–based upon applications of the molecular techniques there is an opportunity to characterize the duodenal and colonic mucosa associated microbiome and associated gut microbiota dysbiosis in patients with various gastrointestinal and extraintestinal diseases. Furthermore, the role of confounders like psychological co-morbidities, medications, dietary practices, and environmental factors on the gastrointestinal microbiome in health and disease also needs to be explored.