Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD ...is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.
The importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying ...the human microbiome. Although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. As such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease. In this Concise Review, we provide a brief introduction to clinicians of the concepts underlying this burgeoning scientific field and briefly explore specific disease states for which the potential role of the human microbiome is becoming increasingly evident, including Clostridium difficile infection, inflammatory bowel disease, colonization with multidrug-resistant organisms, obesity, allergic diseases, autoimmune diseases, and neuropsychiatric illnesses, and we also discuss current and future roles of microbiome restorative therapies.
The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence ...reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.
Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety.
A prospective ...survey-based study was conducted (September 2012–June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant.
Overall, 609 patients underwent FMT; median age was 56 years (range, 18–94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0–6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0–73) post-FMT.
FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.
The pathogenesis of Clostridioides difficile infection (CDI) was recognized with its link to the use of antimicrobials. Antimicrobials significantly alter gut microbiota structure and composition, ...which led to the discovery of the association of this gut perturbation with the development of CDI. A number of factors implicated in its pathogenesis, such as advancing age, proton-pump inhibitors, and gastrointestinal diseases, are linked to gut microbiota perturbations. In an effort to better understand CDI, a multitude of studies have tried to ascertain protective and predictive microbial footprints linked with CDI. It has further been realized that CDI in itself can alter the gut microbiome. Its spore-forming capability poses as an impediment in the management of the infection and contributes to its recurrence. Antibiotic therapies used for its management have also been linked to gut microbiota changes, making its treatment a little more challenging. In an effort to exploit and utilize this association, gut microbial restoration therapies, particularly in the form of fecal microbial transplant, are increasingly being put to use and are proving to be beneficial. In this review, we summarize the association of the gut microbiome and microbial perturbation with initial and recurrent CDI.
The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut ...microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile.
Plain language summary
The Role of the Gut Microbiome in Clostridioides difficile Infection
Introduction:
A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens.
A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile.
CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome.
Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis.
Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance.
It is important to evaluate treatment options to determine their safety and effectiveness.
Methods:
The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens.
They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI:
- Antibiotics
- Monoclonal antibodies
- Fecal microbiota transplantation (FMT)
Results:
Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as:
- Competition for key nutrients
- Production of inhibitory bile acids
- Short-chain fatty acid production
- Lowering the luminal pH
- Production of bacteriocins
Antibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy.
Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome.
FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient’s colon.
Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized.
Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT.
Conclusion:
Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.
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