Poop Pill

Fields covered: Microbiology, Microbiome, Microbiome-based therapy

Together with many other microorganisms, C. difficile can exist harmlessly in our gut¹. They are known collectively as the gut microbiome. The balance of the gut microbiome, or the relative composition of each microorganism in relation to other microorganisms in the gut, is intricately linked to our health². Generally, a balanced gut microbiome translates to good health, while an unbalanced one is often associated with diseases². When our gut microbiome becomes unbalanced³, such as following the use of antibiotics (which kills bacteria aimlessly, killing both the beneficial and harmful ones), it makes room for nasty, disease-causing bacteria – such as C. difficile – to replicate and colonize the gut. Thereafter, C. difficile can release toxins, and in large enough numbers, to stimulate inflammatory pathways and diarrhea⁴ (Figure 1).

You may have encountered the feisty Clostridium difficile (C. difficile) at some point – when you were on the loo!

C. difficile, a type of bacteria, is one of the most common causes of antibiotic- and healthcare-associated diarrhoea¹. C. difficile infection usually follows antibiotic treatment or by ingestion of C. difficile spores¹. Spores are the means by which the bacteria spread. But just because you’ve ingested C. difficile spores doesn’t automatically mean you will get diarrhoea. So what turns this bacteria from a harmless microbe into a stomach-twisting menace?

There are two main ways to treat C. difficile infection. The first is through taking a course of antibiotics to kill the disease-causing C. difficile (naturally, a different antibiotic from the one that might have originally led to the infection)³. Antibiotics might clear the infection, but prolonged usage can lead to antibiotic resistance. This is a huge problem especially for C. difficile infections because they tend to be recurring⁵. This leaves us with the second strategy: to restore the gut microbiome balance. The historical method of doing so is by delivering stool from a healthy donor to the patient, via colonoscopy. (Why stool? The gut microbiome is found in your intestines and what better way to sample your gut microbiome than to collect what is passed out?) This is known as fecal microbiota transplant (FMT) and has been common practice for about 10 years⁵. Colonoscopy, where the doctor inserts an instrument into you, bottom-up, is not the best way of administering a form of treatment because of how invasive it is. Therefore, current therapeutic research is looking into ways of making this safer (as you can imagine, human waste is not the cleanest of things) and easier to administer.

Scientists have recently developed one such method, delivered in a tiny package–an oral pill^5,6. Whilst still in the midst of obtaining approval for sale in the market, it boasts promising clinical trial results and was touted to be as effective as traditional FMT in treating C. difficile infections^5,6. This pill contains microbiome from human stool after purification. The purification process removes most pathogens–harmful microorganisms that are known to cause diseases–leaving spores from a group of bacteria belonging to the phylum Firmicutes. These bacteria can compete with C. difficile for nutrients and space in the gut, and make the host gut environment more hostile for C. difficile survival, ultimately reducing the amount of C. difficile in the gut (Figure 2). Fewer C. difficile translates to lesser toxins released, eventually relieving diarrhoea!

Besides C. difficile-associated diarrhoea, many other diseases, such as neurodegenerative diseases, cardiovascular diseases, and metabolic diseases, are associated with imbalances in the gut microbiome⁷. Microbiome-based therapy, such as this pill containing purified microbiome from human stool samples, is a field with much promise!

A quick and easy introductory video on gut microbiome: https://cdhf.ca/health-lifestyle/introducing-the-human-gut-microbiome-animation/

References

Vedantam G, Clark A, Chu M, McQuade R, Mallozzi M, Viswanathan VK. Clostridium difficile infection: toxins and non-toxin virulence factors, and their contributions to disease establishment and host response. Gut microbes. 2012 Mar 1;3(2):121-34.
Olvera-Rosales LB, Cruz-Guerrero AE, Ramírez-Moreno E, Quintero-Lira A, Contreras-López E, Jaimez-Ordaz J, Castañeda-Ovando A, Añorve-Morga J, Calderón-Ramos ZG, Arias-Rico J, González-Olivares LG. Impact of the gut microbiota balance on the health–disease relationship: The importance of consuming probiotics and prebiotics. Foods. 2021 Jun;10(6):1261.
Clostridium difficile (C. diff) [Internet]. nhs.uk. 2022 [cited 4 July 2022]. Available from: https://www.nhs.uk/conditions/c-difficile/
Burke KE, Lamont JT. Clostridium difficile infection: a worldwide disease. Gut and liver. 2014 Jan;8(1):1.
Servick K. Pill derived from human feces treats recurrent gut infections [Internet]. Science.org. 2022 [cited 4 July 2022]. Available from: https://www.science.org/content/article/pill-derived-human-feces-treats-recurrent-gut-infections
Feuerstadt P, Louie TJ, Lashner B, Wang EE, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, Korman LY. SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. New England Journal of Medicine. 2022 Jan 20;386(3):220-9.
Chen Y, Zhou J, Wang L. Role and mechanism of gut microbiota in human disease. Frontiers in cellular and infection microbiology. 2021:86.