The Role of a Sequencing-based Clinical Intestinal Screening Test in Patients at High-risk for Clostridium Difficile and Other Pathogens

A Case Report

Maureen Hitschfeld; Elena Tovar; Sarah Gupta; Elisabeth M. Bik; Christina Palmer; Michael C. Hoaglin; Daniel E. Almonacid; Jessica Richman; Zachary S. Apte

Disclosures

J Med Case Reports. 2019;13(9) 

In This Article

Background

The human gut microbiome consists of trillions of microorganisms that populate the human gut, and its genome is approximately 100 times larger than the human genome.[1] It is considered by some to act as an organ due to the number of physiological functions that it performs for the host.[2] Under normal conditions, commensal microbes and their hosts enjoy a symbiotic relationship. In addition, a greater diversity of microorganisms is generally an indicator for gut health, presumably because it offers greater resistance to perturbation.[3,4] Intestinal dysbiosis refers to identifiable abnormality of the gut microbiota, either due to low microbial diversity, suboptimal levels of commensal beneficial microbes, excess of potentially harmful microorganisms, or presence of pathogenic microbes.[5,6] Maladaptive alterations of the microbiome composition result in deficient functions, which are associated with various prevalent conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), type 2 diabetes, prediabetes, obesity, non-alcoholic fatty liver disease, atherosclerosis, cardiovascular disease, kidney stones, among others.[7–13] Interestingly, the host interactions with the gut microbiome and its composition are not static, but rather dynamic and modifiable over time.[14] Diet, medication, and lifestyle are important determinants of microbial composition.[15–17] However, the largest and most immediate effects on microbial composition are related to the use of antibiotics, which may negatively affect the composition and function of the gut microbiota and consequently have an impact on patient well-being.[18]

In the USA, IBS is the most common functional gastrointestinal (GI) disorder, with a reported prevalence between 10 and 25%; women exhibit prevalence rates 1.5-fold to 3-fold higher than men.[19] This chronic condition is characterized by abdominal pain associated with bowel dysfunction. Although IBS etiology is not completely understood, it is regarded as multifactorial. Contributing factors include intestinal motility, inflammation, genetics, immunology, psychology, and diet.[20–22] There are several subtypes of IBS, including IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M), and unclassified (IBS-U).[23] Initial treatment may include dietary and lifestyle changes. In particular, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet shows benefits in the management of IBS.[24,25] Cognitive behavioral therapy has also been shown to be successful in managing IBS symptoms because anxiety and depression are commonly seen in patients with IBS.[26] Patients with more severe symptoms may also benefit from pharmacologic therapy to address predominant symptoms. A diagnosis of IBS is difficult to make. It has been estimated that up to 75% of cases of IBS go undiagnosed.[27] Studies show that patients with IBS have an underlying alteration of their gut microbiota composition.[28–31] For instance, it is known that abundance of the genus Veillonella is positively associated with IBS, while the relative abundances of genera Alistipes, Bifidobacterium, and Lactobacillus and the species Collinsella aerofaciens are inversely associated with IBS.[16,32–35]

Clostridium difficile is currently the leading cause of infectious nosocomial diarrhea in the USA; the incidence and severity of C. difficile infection (CDI) are increasing and are associated with increased health care costs.[36]C. difficile is an opportunistic pathogen, with toxigenic strains known to cause high levels of morbidity and mortality. There are a number of well-known risk factors that have been linked to CDI, including exposure to antibiotics and gastric acid suppressants, hospitalization, GI surgery, working in a health care setting, and the presence of underlying disease or immunosuppression.[37,38] According to the Centers for Disease Control and Prevention, C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011.[39] Toxicity from CDI is mediated by two exotoxins: toxin A and toxin B.[40] Colonization of the gut microbiota with C. difficile can be innocuous and asymptomatic; however, if the normal intestinal microbial architecture is disrupted, proliferation of opportunistic C. difficile may occur. There is evidence that CDI risk in C. difficile carriers is nine times higher than in non-carriers,[41] and in healthy adult patient populations, as many as 15% of people may be colonized with C. difficile; prevalence rates appear to vary widely depending on the population.[42]

There are limited data on what role CDI may play in patients with IBS. A cohort study showed that a new-onset of IBS is common after CDI. Infection duration, anxiety, and higher body mass index (BMI) were found to be associated with higher risk of the diagnosis of C. difficile in patients with post-infectious IBS.[43] Another study suggested that a subpopulation of patients with IBS in the absence of known risk factors for C. difficile may be susceptible and predisposed to CDI.[44] In this small study, C. difficile incidence among patients with IBS (5 out of 87) was higher than in the control group (1 out of 88), albeit not statistically significant, and the positive cases were found among all three IBS subtypes.[44]

Here we present a case of a patient with a diagnosis of IBS-D, who used an at-home, self-administered, sequencing-based clinical intestinal microbial screening test (SmartGut™, uBiome Inc., San Francisco, USA) to identify the presence of C. difficile in the setting of multiple chronic conditions. Treatment for C. difficile led to resolution of her symptoms.

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