More on 'Bugs as Drugs'

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.

C. difficile infection can 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!

The Potential Role of Our Microbiome Ecosystems

For those who like these pop-sci articles on the still somewhat conjecture-like but very inspiring theories about the role of our intestinal microbiome in health and disease, here's a link to an article from The Economist (18 AUG 2012):

The Human Microbiome: Me, myself, us

And let me reiterate: We still don't know much about mikro-eukaryotes in all this... do they play a role as well? And how do they cope with different types of microbiomes?

Anyways, enjoy!

On Faecal Bacteriotherapy

For those of you who read my most recent blog post and who went on to read Carl Zimmer's article in The New York Times about gut flora transplantation on a woman suffering from chronic Clostridium difficile diarrhoea: The concept of faecal bacteriotherpy is maybe not that new. Allegedly, it dates back to Pliny the Elder and others, who prescribed orally ingested faeces to cure maladies! Stools were, however, incinerated first, and only the ashes ingested.

Pliny the Elder and others with him allegedly recommended  ingesting the ashes of faeces to cure disease.

In less ancient times - in 1989 to be more preciese - Tvede and Rask-Madsen from Copenhagen, Denmark (Statens Serum Institut and The Danish State Hospital) reported on bacteriotherapy for chronic relapsing C. difficile diarrhoea in six patients. They hypothesised that absence of Bacteroides results in chronic relapsing C. difficile diarrhoea, and that its presence may prevent colonisation by C. difficile. In the current issue of Microbe Magazine, Young and Aronoff describe some of the mechanisms that may be involved in our indigenous gut flora's ability to prevent the colonisation of potentially pathogenic bacteria such as C. difficile. These include: (1) occupying space (physically preventing contact by newly arrived microbes with the host), (2) directly impairing the growth or germination of C. diffıcile, (3) withholding nutrients or germinants from C. diffıcile, and (4) shaping the host adaptive and innate immune responses.

Hence, the concept of dysbiosis and the ideas of manipulating the gut flora in order to "restore order" have been going on for a long time. Metagenomics, however, will assist us in exploring exactly what is happening in much more detail and in a much broader and standardised context than previously possible. We will be able to predict shifts in the structure, function and interaction of microbial communities - hopefully including micro-eukaryotes such as fungi (the "mycobiome") and common protists such as Blastocystis and Dientamoeba (maybe we can call it the "protistome"?), - and any influence of diet, pro- and antibiotics.

And fortunately, the focus on metagenomics continues: While CMI just launched a themed issue on metagenomics advances (see previous blog post), even Science and Science Translational Medicine now dedicated an entire joint issue to "The Gut Microbiota", and I hope to be able to address one or two of these papers soon. Until then, here's a bit of suggested reading:

'Bugs as Drugs'

Tvede, M., & Rask-Madsen, J. (1989). Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients The Lancet, 333 (8648), 1156-1160 DOI: 10.1016/S0140-6736(89)92749-9

Young and Aronoff (2012). Clostridium difficile linked to disrupted gut microbiota. Microbe Magazine (ASM): http://goo.gl/FIZmC 

Mueller, K., Ash, C., Pennisi, E., & Smith, O. (2012). The Gut Microbiota Science, 336 (6086), 1245-1245 DOI: 10.1126/science.336.6086.1245