This morning, I was doing a lazy ramble through my favourite blogs and found a post by Carl Zimmer on 'Bugs as Drugs' - primarily on probiotics. And I just came to realise that there is a very interesting tendency these years of using bugs as drugs in a variety of fields.
We are all very much aware of the worries about the increase in antibiotic resistance in bacterial and other pathogens. Moreover, it appears that sometimes antibiotic treatment leads to imbalance in the intestinal microbiota (dysbiosis); a well-known example is intractable Clostridium difficile infections which can potentially lead to pseudomembranous colitis.
Earlier this year, an article appeared in the renowned The New England Journal of Medicine on a randomised, controlled treatment study on duodenal infusion of donor faeces for recurrent C. difficile. The researchers found that the infusion of donor faeces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin, the drug usually recommended in this situation. In fact 15/16 patients had resolution of C. difficile-associated diarrhoea upon first or second infusion; however, it might be worthwhile 'shopping around' for the right donor.
And so, how are these faecal transplants developed and administered? Well, it appears that donors are volunteers who have been through a selection process based on a questionnaire on risk factors of infectious diseases. Then donor faeces is screened for parasites (including Blastocystis and Dientamoeba - yes, it warms my heart to see this so explicitly spelled out in the paper... but I wonder which methods were used - it doesn't say!) and enteropathogenic bacteria. Moreover, blood samples from donors are screened for e.g. HIV, hepatitis and antibodies against e.g. Entamoeba histolytica and Strongyloides. Next, a donor pool is created with repeated screening every 4 months. On the day of infusion, faeces is collected by the donor and immediately brought to the hospital, where it is diluted with 500 mL of sterile saline. The solution is stirred, and the supernatant strained and poured in a sterile bottle. Within 6 h after collection of the faecal sample by the donor, the solution is infused through a nasoduodenal tube (2 to 3 mintues per 50 mL). Patients are subsequently monitored for 2 h. Apparently, this is how it works!
Interestingly, it appears that ways of biologically controlling and manipulating infectious and non-infectious diseases circumventing the use of antibiotics are navigable and on the rise: I have previously blogged on the hygiene hypothesis, on dirtying up our diets, and on helminth therapy of colitis, and I'm currently involved in a study on Trichuris suis ova treatment of a patient with psoriasis, a chronic inflammatory skin disease; a study aiming to determine whether helminth therapy remedies flare-ups.
Exploitation of organisms to combat diseases may in the future include virotherapy of parasites. There is a paper out just now in Trends in Microbiology elaborating on the hypothesis that it might be possible to manipulate viruses to control certain parasites. A number of viruses are already known to infect parasites pathogenic to humans (e.g Giardia, Cryptosporidium, Trichomonas, Acanthamoeba and Leishmania) and plants (e.g. Phytophthora). So far, viruses have mainly been explored as a means of controlling bacteria by using bacteriophages, and the authors encourage studies into investigation of viruses and virus-like particles in parasites (Importantly, another angle to this is the possibility of viruses inducing differential gene expression among infected and non-infected parasites... something that should also be explored and not ignored).
And... I guess that everyone is familiar with the use of maggots for wound healing? Don't worry, I'll save pics for later...
Anyway, the use of bugs as drugs is certainly an interesting field that challenges our current inclination to seeing bugs as something that should always be avoided and that may potentially remedy a variety of diseases along with presenting solutions to the problem of drug resistance or adverse drug reactions.
Suggested reading:
Hyman P, Atterbury R, & Barrow P (2013). Fleas and smaller fleas: virotherapy for parasite infections. Trends in Microbiology PMID: 23540830
van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, & Keller JJ (2013). Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England Journal of Medicine, 368 (5), 407-15 PMID: 23323867
Weinstock JV (2012). Autoimmunity: The worm returns. Nature, 491 (7423), 183-5 PMID: 23135449
