The role of the gut microbiome in colonization resistance and recurrent infection.

Therap Adv Gastroenterol

Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Published: November 2022

AI Article Synopsis

  • The human gut microbiome is crucial for overall health and helps prevent infections, but disruptions can lead to diseases, especially after antibiotic use.
  • Standard antibiotics may not resolve microbiome imbalances and can actually worsen the situation, which is particularly problematic for patients with recurrent Clostridioides difficile infections (CDI).
  • Fecal microbiota transplantation (FMT) shows promise in restoring gut health but faces challenges such as safety concerns and the need for more regulated biotherapeutic options.

Article Abstract

Unlabelled: 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 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 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

Plain Language Summary: 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 infection (CDI), caused by the bacterium .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. 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) 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 bacteriocinsAntibiotic 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 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 FMT. Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9679343PMC
http://dx.doi.org/10.1177/17562848221134396DOI Listing

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