Probiotics & Fecal Transplants

'But my dear Sebastian, you can't believe things because they are a nice idea.'
'But I do, that's how I believe.'

Brideshead Revisited by Evelyn Waugh

The quotation is taken from a classic novel in English literature that tells the story of how the hero, Charles Ryder, is befriended by the members of an aristocratic family in the years leading into the Second World War. At this very moment in the novel, the scion of the family, Sebastian Flyte (who happens to be drunk), has just said that he believes in Christianity because he likes the idea of the 'Ox and the Ass and the Wise Men'. Ryder is an atheist from a lower social class and a newcomer to the dissipations of the establishment set, which are ended by the upheaval of the war in which all classes become involved.

Believing things without evidence, anti-establishment sentiments and potentially turning the world on its head are all themes that might be applied to the role of intestinal microbes in disease. As doctors trying to deal with this this new medical theism, who are we: the Ox or the Ass or the Wise Men?

We all now believe, more or less, in good intestinal bacteria. Actually, 90% of our cells and 99% of all our genes are the prokaryotes that inhabit our lower intestine. So we are all really walking microbial cultures. Believing in good bacteria becomes essential for our self-respect.

At medical school we were terrorised by diagrams showing all possible biochemical reactions on one enormous wall-chart. What the biochemists did not tell you (I must take some responsibility, because for a time I was one of them) is that most of these reactions only take place in bacteria, so much of our metabolism also depends on our good bugs.

It should follow, quite logically, that the more good bugs you have the better. A short tour of the Internet can amply confirm this view. Probiotics are the panacea of our time: worthy successors to leaches, blood-letting, ginseng, homeopathy, indiscriminate antibiotics or anti-TNF infusions in Crohn's disease patients with strictures. Probiotics are often tried when nothing else works. Supporting this practice, one can find published claims that they benefit infants, immunity, mental health, mouth and teeth, lung cancer, asthma, influenza, atherosclerosis, blood pressure, cirrhosis, stomach ulcers, food poisoning, IBD, colorectal tumours, cervical cancer, dermatitis, etc., etc. (http://probiotics.org/benefits/: reprinted without permission). Wow, what a list! I tried to think of a condition that might not benefit, so I randomly tried typing "Wegener's granulomatosis AND probiotic benefit" into Google and ended up with 216'000 results. In despair, and still in a religious frame of mind, I thought that the Old Testament High Priest Melchizedek could not possibly be linked with probiotic benefit, yet I got 32'000 hits from the link (albeit mainly because of proselytsing about probiotics from his present day name-sakes).

These good bacteria are marketed on a 'generally recognised as safe' basis, even if their broad efficaciousness is not 'generally believed to be true': at least by the Wise Men. The new idea is that there should be some basis for the claims on the bottle: this criterion probably generates more work for lawyers than it does for scientists. I was once on a panel in the US that debated marketing rules for probiotic preparations. As you might imagine, the representatives of the probiotic marketing companies were profoundly opposed to suggestions that they should adopt formal testing as required for drug licensing.

Probiotics are often, but not always, harmless.  We see patients that take so many probiotics that their symptoms can be ascribed to (culture proven) 'pseudobacterial overgrowth' - because they are contaminating the small bowel with large numbers of ingested live microbes. This problem is definitely augmented if the stomach acid is coincidentally neutralised by adding PPIs to this cocktail.

But one would be an Ox or an Ass to be a probiotic (or a good bug) atheist. Good bugs can definitely help. Although proper randomised controlled trials have been disappointing in many conditions including IBD, probiotics can help the recovery of infectious diarrhoea. Used judiciously they benefit post-infectious enteropathy and its overlap with IBS-D.

The problem is that the consortia of microbes in the intestine are very delicately balanced and the whole microbial niche is utterly and completely full. They are living in an overcrowded city with intimate relationships, which make the back streets of Marrakech look as if they have plenty of open space. Our intestinal microbes have formed network alliances to exchange chemicals with each other and achieve some sort of harmony, but they do not like strangers. No immigrant to Switzerland could, by chance, suddenly find an empty house where he is allowed to take up residence and bring up his family. The immigration policy in the gut is much more fierce: as a microbe you have to be extremely fit for the fight to stay in and reproduce, or you end up in the toilet. Most probiotics are just passing from mouth to anus, without doing very much to the rest of the microbiota, or to us.

Since one warrior is rarely enough, how about sending in the army? For this we have stool transplantation. The Internet sites are also full of lay advice about this, and even will tell you how to do it at home (thepowerofpoop.com/.../fecal-transplant-instructions...). Basically one person's shit is homogenised and infused into the intestine of the recipient (along with HIV, Hep.B/C etc. if you are not careful). Unsurprisingly, this can be rather more effective in some conditions than in others. We do fecal transplants in the Inselspital for patients with recurrent C. difficile infections, but with detailed screening of the donor, microbiological controls and follow-up considerably more sophisticated than given by the 'powerofpoop' website above. Sadly this is still a very empirical procedure, although our group and others are working hard to understand the basis of why it works or fails. We are also working to develop systematic preparations that will eliminate the bystander infective risk of undefined microbial mixes.

In the end, our interactions with our microbiota are much more than a nice idea. They really happen and they are important for disease: we hope to be able to change the course of many conditions. Sadly the microbiota is immensely complex and notoriously difficult to manipulate. The technical challenges will be overcome, but like much of modern technological medicine, the procedures to be standardised and developed on rational lines with proper trials.

We end almost as we started; with an Englishman named Ryder, this time not Charles, but Samuel, founder of the famous Ryder Cup. People can hit a golf ball with a wild swing and their eyes closed if they want, but they will be very unlikely to get it into the hole or to win the tournament.
 
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