Sunday, July 31, 2016

A load of crap in Gartnavel

This came to me via Facebook from Wally Courie:

Poop Pill’s Surprise Failure Shows That the Microbiome is Still a Mystery

The original faecal transplant work was done in Glasgow and got written up here:

Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series.

Many years ago, probably around 2006 when the above paper was being written/published, I attended a presentation at a probiotics meeting in central London by a medic from Gartnavel General Hospital in Glasgow. Might have been by MacConnachie himself. He was quite deadpan, described their very simple procedure for obtaining, filtering and administering the faecal transplant by NG tube. You can read the abstract of the paper to get some idea of the success rate of the procedure. Hint; very high.

What really stuck in my memory was his comment was that, as they removed the NG tube, the patient cured. Many of these these folks hadn't left the house, often never left the loo, for years before referral. Their next bowel movement was going to be normal.

With a success rate as high as documented there has never been a double blind placebo controlled trial. I rather like that.

So I can imagine him watching the development (as I did) of the multiple probiotic capsule which was (or wasn't!) going to cure C. difficile gut-rot without all of the "ick-factor" of the trip to Gartnavel. Then quietly going in to work to cure some more people, assisted by a pooh sample.



raphi said...

Hi Peter,

On Gut bugs:
- The success rate of the poop pill on C. diff. is impressive but how quickly it does so might be even more impressive.
- When talking gut bugs, I find it useful to ask how is 'diversity' measured - is it genetic diversity (microbiome)? or species diversity (microbiota)? Of course, horizontal gene transfer has a habit of blurring these lines.
- From your link ( "[...] 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified [...]"
- From <> ( & authors' comments ( "Importantly we found that although a long transit time associates with high microbial richness, it also gives rise to higher levels of potential deleterious protein degradation products, suggesting that a rich bacterial composition in the gut is not necessarily synonymous with a healthy digestive system, if it is an indication that food takes a long time to travel through the colon."

While you were away:
- Chris Materjohn
1) Carbs + Ketones episode "Did you know that adding MCT oil to your pasta is more ketogenic than restricting your carbohydrates to ten percent of calories?"
He argues that including enough insulinogenic foods with MCTs gets you the benefits of: elevating ketones, getting plenty oxaloacetate into the TCA (avoiding muscle catabolism), provide superior oxidative stress management from insulin's GSSH recycling as well as its hormonal balancing act with thyroid/cortisol
2) Keto + CrossFit episode "[...] it doesn’t really get to the heart of the questions I would be interested in, which are these: how would a ketogenic diet impact maximal performance on weight-lifting sets of 5-12 reps, or in sports involving short bursts of energy such as football, basketball, baseball, soccer, and tennis, and do the hormonal adaptations to the diet ultimately have the potential for negative impacts on thyroid hormone, cortisol, LDL-cholesterol, and sex hormones?"
He's happy that with enough protein and exercise stimulus muscle loss is mostly avoided and fat loss can happen, but worries (once again) about hormonal balance (thyroid/cortisol) and predicts that maximal efforts (1-4 reps of heavy weights) might be blunted.

Not sure if these sorts of keto discussions are of interest but i thought I'd put them to you, just in case.


Boundless said...

From the failure article on TR: "Here, spores from good bacterial species are isolated and encapsulated in pill form, while disease-spreading microbes like Listeria and Salmonella are eliminated."

I'm thinking that one hint at why the results were "inconsistent" with expectations is found in the next paragraph: "The goal is to reintroduce the diverse population of microbes…"

Bacteria are only a subset of microbes. The spectrum of microbes in the human gut is already known to include bacteria, eukaryotic parasites, fungi (e.g. yeasts), protozoans and viruses. A recent paper is strongly suggestive that there might also be as-yet unknown Domains of life.

Genetic testing of the microbiome often considers only bacteria. All but one or two commercial probiotic products are just bacteria.

These life forms further may have material inter-dependencies with each other. This means that there may be no clean classification as "beneficial" or "pathological" for each. Relative populations and diversity probably matter.

Seres' site is vague on exactly what the "keystone organisms" are that they use in SER-109. It may include some microbes ("spores" in some reports) other than bacteria, but we are still constrained by the limits of our knowledge about the microbiome.

Although it's surprising that FMT works as well as it does, it's less surprising that oral probiotics, probiotic enemas, isolated microbes, and isolated fermentation byproducts are often less successful.

I also predict that a reliably successful and sustainable treatment program for dysbiosis must include remediation of the root causes of the problem. A course of FMT might not cure for long if the adverse provocations are left in place (and it might be permanent if the problem was simply an extinction from decades ago).

We don't know precisely what the key remediation targets are, but I won't be surprised it's multi-factorial, and the problems include:
Ѯ excessive deliberate antibiotic use
Ѯ diets low in fermentable substrate, and
Ѯ diets high in substrates that foster adverse micros
Ѯ pervasive second-hand antibiotics in foods
Ѯ pervasive second-hand anti-fungals in foods
Ѯ pervasive non-native halogen compound exposure generally, esp.
Ѯ chloramine in municipal water (a very persistent agent)
Ѯ lack of routine exposure to soil-based micros to top-off the populations
Ѯ common micronutrient deficiencies that bias the populations
Ѯ and now for something, completely different
Ѯ etc.

Entirely apart from the microbiome itself, there are other pervasive modern dietary insults that directly degrade the gut wall, and overall health. Fixing the microbes is of limited benefit in a leaky gut.

cavenewt said...

What Boundless said sounds spot-on.

Another failure of hubristic Western reductionism.