Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder characterized by recurring abdominal pain associated with evacuation or changes in bowel habits (ie, stool form and stool frequency). IBS is commonly subclassified based on the predominant bowel habit (ie, constipation-predominant IBS, diarrhea-predominant IBS [IBS-D], or mixed IBS [an occurrence of both constipation and diarrhea]). A common disorder, IBS is estimated to affect ~11% of adults worldwide. The pathogenesis of IBS is not completely understood, but is considered multifactorial, with the immune system, gut–brain axis, and gut microbiota thought to play roles. Indeed, increased concentrations of proinflammatory cytokines (ie, interleukin-6 and tumor necrosis factor-α) have been observed in patients with IBS compared with healthy individuals. Further, interactions between the gut microbiota and central nervous system (ie, gut–brain axis) are thought to play a role in IBS pathogenesis, and the interaction is likely bidirectional. For example, psychiatric comorbidities (eg, anxiety and depression) are common in patients with IBS. Abdominal pain, a key component of the clinical definition of IBS, is one of the most common symptoms resulting in patients with IBS seeking consultation with a health care provider. The management of IBS is based on specific GI symptoms (eg, diarrhea and constipation) and the severity of those symptoms. However, patients with IBS may experience variations in predominant symptoms and/or IBS subtypes during their lifetime, necessitating adjustments in management approaches.
IBS has a substantial negative effect on patients. Data suggest that patients with IBS-D experience significantly greater decreases in health-related quality of life and increased impairment of daily activities compared with healthy individuals (p<0.001 for both comparisons). In addition, work absenteeism (ie, the percentage of work time missed related to health issues) and presenteeism (ie, the percentage of impairment experienced during work time related to health issues) are significantly more common in patients with IBS-D than in healthy individuals (absenteeism, 5.1% vs 2.9%, respectively; p=0.004; presenteeism, 17.9% vs 11.3%; p<0.001).
The aim of the current article was to provide an overview of the role of short-course therapy with rifaximin in the management of patients with IBS-D.
A PubMed search of English language articles available through May 9, 2017, was conducted using the following keywords to identify relevant articles and studies performed in adult humans: “irritable bowel syndrome,” “pathogenesis OR pathophysiology,” “gut dysbiosis OR microbiota,” “small intestinal bacterial overgrowth,” “breath testing,” “treatment,” “management,” “antibiotic,” and “rifaximin.”
Intestinal dysbiosis, or alterations in the quantity or composition of GI-associated microbiota, has been observed in patients with IBS. For example, results of a meta-analysis demonstrated that the expression of Lactobacillus and Bifidobacterium differed significantly between patients with IBS-D and healthy individuals (p=0.02 and p=0.001, respectively). In addition, patients with IBS-D appear to have significantly lower concentrations of aerobic bacteria than that of healthy individuals (1.4×10 7 vs 8.4×10 8 colony-forming units [CFUs]/g feces, respectively; p=0.002).
In a longitudinal study, gut microbial instability (ie, differences in microbial numbers or composition; determined using culture-independent molecular analysis [ie, PCR-denaturing gradient gel electrophoresis]) was greater in patients with IBS than in healthy individuals during a 6-month period (43% vs 29%, respectively). This greater instability (ie, temporal changes) in the gut microbial composition versus healthy individuals has also been specifically shown in patients with IBS-D. In addition, when the gut microbiota of a pooled IBS subtype population was analyzed by IBS symptom severity, patients with severe IBS (defined as IBS severity score >300, maximum score of 500) had decreased microbial diversity, increased Bacteroides, and a lack of Methanobacteriales compared with the gut microbiota of healthy individuals. To date, studies comparing the gut microbiota of patients with IBS with that of healthy individuals have been limited to demonstrating an association between dysbiosis and IBS; cause and effect remain to be elucidated.
Small intestinal bacterial overgrowth (SIBO), characterized by quantitative and qualitative alterations in bacteria in the small intestine, is a diagnosis that may be considered in patients with nonspecific symptoms of abdominal pain, bloating, and diarrhea. Further, patients who use proton pump inhibitors (PPIs) may be at a greater risk of developing SIBO, as findings of a meta-analysis of 19 studies reported that PPIs significantly increased the risk of SIBO (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2–2.4). However, a study of patients undergoing upper GI tract endoscopy (n=897) showed no association between PPI use and SIBO. In 2017, the North American Consensus group on hydrogen- and methane-based breath testing proposed a bacterial concentration of >10 3 CFU/mL following aspiration of small intestine fluid and subsequent culture as meeting the threshold for a diagnosis of SIBO. In one study, more patients with IBS (43%) achieved a positive culture threshold of ≥5×10 3 CFU/mL compared with healthy individuals (12%; p=0.002). Conversely, a retrospective study of patients with IBS failed to show an association between IBS and SIBO (OR, 0.2; 95% CI, 0.1–0.7). However, obtaining small intestinal aspirate samples for culture is an invasive procedure, and differences in findings may be related to inconsistencies in sample collection, in vitro growth, and the potential for contamination (ie, bacteria from outside the small intestine).
Although criteria for diagnosing IBS are based on patient symptoms, breath testing – a method that measures the production of gases (eg, hydrogen and methane) that result from bacterial fermentation of orally administered but unabsorbed carbohydrates (eg, glucose, lactose, and lactulose) in the GI tract – may be used for various reasons, such as to determine the presence of SIBO or carbohydrate malabsorption. A meta-analysis of 11 studies found that positive breath tests occurred more frequently in patients with IBS (n=1076) than in healthy individuals (n=509; OR, 4.5; 95% CI, 1.7–11.8; p=0.003). A study published after that meta-analysis was conducted reported that 23.7% of patients with IBS had positive breath test results compared with 2.7% of healthy individuals (p=0.008). That study also reported that, based on breath test results, SIBO was more prevalent in patients with IBS-D (37.0%) than in patients with other IBS subtypes (12.5%; p=0.02). However, other studies have failed to demonstrate an association between SIBO (based on breath testing) and IBS. Thus, bacterial culture and breath-testing data appear to suggest that at least a subset of patients with IBS may have alterations in their gut microbiota. These findings, which remain to be confirmed by larger, well-designed studies, suggest that empiric treatment of patients with IBS thought to have comorbid SIBO may be warranted.
Given the multifactorial nature of IBS, various types of therapeutic options are prescribed to help manage the symptoms of IBS-D (Table 1). To manage individual symptoms of IBS, most of these agents must be administered daily, either long term or as needed (eg, antispasmodics or peppermint oil for abdominal pain), or administered off-label to manage global IBS symptoms alongside psychiatric comorbidities (eg, tricyclic antidepressants or selective serotonin reuptake inhibitors may improve coexisting anxiety or depression, as well as decrease visceral pain).
