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The Role of the Microbiome in C. difficile Infection and Its Impact on Overall Health

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Hippocrates was credited with saying “All disease begins in the gut.” Twenty-five hundred years later, we’re learning he was pretty close.

Although not all disease starts there, the gut is home to an important defense against disease and infection: the gut microbiome. As pharmacists, it is essential to stay up to date with key research and findings to further support patients.

What is the gut microbiome?

Sometimes called the “forgotten organ,” the gut microbiome is a thriving community of trillions of microorganisms representing 500 to 1000 species of bacteria, viruses, and fungi.1-6

These diverse species, together called gut microbiota, mostly live deep within the colon, living inside and outside the gut.7

The gut microbiome maintains a symbiotic relationship with the cells that make up the walls of the gut mucosa. It forms a protective barrier between the intestinal walls and its contents, protects against the growth of harmful colonies of microbiota, and promotes overall health.8-10

Although our understanding of the microbial function of the microbiota continues to evolve, bacteria within the gut microbiome ecosystem have been shown to play important roles in digestion, metabolism, and synthesis of beneficial substances including vitamins. The microbiome also helps combat infection and inflammation by interfacing with and modulating our immune systems. Some of these functions can be performed by diverse bacteria belonging to different phyla, while other functions are performed in a complementary or symbiotic fashion by select microbiota.11

Composition of the gut microbiome

The gut microbiome contains a large and diverse mix of microbiota, which is essential to overall health. In some cases, an imbalance in the gut microbiome can occur leading to a state of dysbiosis, which has been connected to a wide range of diseases, such as obesity, inflammatory bowel disease, liver disease, and infections.7-12

When the volume and diversity of the gut microbiome are disrupted, and key bacteria are depleted, dysbiosis is the result.

Two of the most prevalent bacteria within the gut are Bacteroidetes and Firmicutes.2,13 Each plays a different role. Bacteroidetes have immunomodulatory effects, whereas Firmicutes have anti-inflammatory effects and fortify the gut’s barrier. These bacteria are important to help maintain balance in the gut microbiome.14-18

Causes and impact of dysbiosis

Dysbiosis is associated with diet, hygiene, and medications, including antibiotics.7,19,20 It has also been linked to a range of gastrointestinal (GI) conditions, such as irritable bowel disorder, colitis, and gastric infections, which can flourish when healthy bacteria are depleted, leaving room for harmful ones to grow.7,17,18

One of these pathogens is Clostridioidesdifficile, which may cause a serious and extremely contagious GI infection that affects nearly 500,000 people in the United States each year, often after exposure in hospitals, and which kills nearly 30,000 people per year.21

C. difficile infectionis treated with antibiotics; however, because antibiotic use, especially prolonged use, can lead to dysbiosis, the infection recurs in up to 35% of patients. Of these, up to 65% experience multiple bouts of C. difficile infection, leading to a vicious cycle of recurrence.17,22

How can we break the cycle of recurrence of C. difficile infection?

The first step to reducing recurrent C. difficile infections is prevention. This may include frequent handwashing with soap, as well as cleaning and disinfecting surfaces that could be contaminated.

Be aware that alcohol-based hand sanitizer gels will not kill C. difficile infection. Exercise caution by controlling contact and wearing personal protective equipment when caring for someone with C. difficile infection.23,24

When dysbiosis occurs, the best approach to restoring balance in the gut microbiome is to repopulate the gut with a mix of diverse microbiota.7,17,18

As scientists learn more about the gut microbiome, they are uncovering ways to harness its power and address serious diseases, including C. difficile infection and recurrence.

Why do pharmacists need to know more about gut microbiome health?

As frontline health workers, pharmacists are in a position to educate patients about the importance of a healthy microbiome and how dysbiosis and infections may be avoided. The best way pharmacists can promote good gut health is through promotion of a healthy diet and appropriate use of medications. For medications, pharmacists can guide use of agents that may precipitate or contribute to dysbiosis (e.g. antimicrobials, proton pump inhibitors).

In accordance with best antimicrobial stewardship practices, pharmacists should promote use of the narrowest spectrum antimicrobial agent used for the shortest possible duration to minimize collateral damage on the microbiome.Additionally, pharmacists can also help patients understand the benefits and limitations of probiotics and most importantly, they can guide patients to seek medical care if C. difficile infection recurs.

To learn more about the gut microbiome, visit PowerofMicrobiome.com.

References

  1. Baquero F, Nombela C. The microbiome as a human organ. Clin Microbiol Infect. 2012 Jul;18 Suppl 4:2-4.
  2. Gilbert JA, Blaser MJ, Caporaso JG, et al. Current understanding of the human microbiome. Nat Med. 2018;24(4):392-400.
  3. Antharam VC, Li EC, Ishmael A, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51(9):2884-2892.
  4. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836.
  5. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: A new clinical frontier. Gut. 2016;65(2):330-339.
  6. O’Hara, A. M., & Shanahan, F. (2006). The gut flora as a forgotten organ. EMBO reports, 7(7), 688–693. https://doi.org/10.1038/sj.embor.7400731
  7. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14(1):20-32.
  8. Bien J, Palagani V, Bozko P. The intestinal microbiota dysbiosis and Clostridium difficile infection: Is there a relationship with inflammatory bowel disease?Therap Adv Gastroenterol. 2013;6(1):53-68.
  9. Ley R, Hamady M, Lozupone C, et al. Evolution of mammals and their gut microbes. Science. 2008;320(5883):1647-1651.
  10. Mazmanian S, Liu C, Tzianabos A, Kasper D. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122(1):107-118.
  11. Kho, Z. Y., & Lal, S. K. (2018). The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Frontiers in microbiology, 9, 1835. https://doi.org/10.3389/fmicb.2018.01835
  12. Allaband C, McDonald D, Vázquez-Baeza Y, et al. microbiome 101: studying, analyzing, and interpreting gut microbiome data for clinicians. Clin Gastroenterol Hepatol. 2019 Jan;17(2):218-230. Epub 2018 Sep 18.
  13. Flores GE, Caporaso JG, Henley JB, et al. Temporal variability is a personalized feature of the human microbiome. Genome Biol. 2014;15:531.
  14. Wexler AG, Goodman AL. An insider’s perspective: Bacteroides as a window into the microbiome. Nat Microbiol. 2017;2(1):17115.
  15. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome.Science. 2006;312(5778):1355-1359.
  16. Kurokawa K, Itoh T, Kuwahara T, et al. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res. 2007;14(4):169-181.
  17. Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota.Science. 2013;341(6141):1237439.
  18. Li X, Kang Y, Huang Y, et al. A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model. Biomed Pharmacother. 2021;137:111290.
  19. Weiss GA, Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017;74(16):2959-2977.
  20. Riaz Rajoka MS, Shi J, Mehwish HM, et al. Interaction between diet composition and gut microbiota and its impact on gastrointestinal tract health. Food Sci Hum Wellness. 2017;6(3):121-130.
  21. Lessa FC, Mu Yi, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-834.
  22. Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: Fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55 Suppl 2(Suppl 2):S154-S161.
  23. Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044.
  24. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infection. Am J Gastroenterol. 2013;108(4):478-498.

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