Manipulating the Microbiome: Miracle Cure or Medical Minefield?

26th December 2016by victoriafenton0

OK – for those of you who have stuck through the mental health blogs and the long, random, convoluted, difficult to explain, nuanced takes on internal biological/psychological frameworks…

Here you have a simple blog on bugs!  (OK, as simple as I can make it… which is actually not that simple…)

I alluded to the fact that I was going to write something on this in my last post on identity and how the brain is built on biology.  There, I was talking about bugs in the context of the regulatory and signalling influence of gut microbiota on brain states.

It may have been clear from the references I used there that the field of microbiome research is in its infancy – not in terms of the time spent researching, but in terms of the reach of the research.  Now, you could be forgiven for thinking that we know a lot about gut bacteria because everyone who is anyone recommends taking probiotics, prebiotics and resistant starch etc.

However, I’m hesitant about the consensus which creeps into recommendations, intimating that we know exactly what we’re doing when it comes to microbiome health.  Because quite frankly, no matter what anyone says, whilst we’re learning a lot and we do know that the microbiome is very important – to say that we know what we’re doing is… well, it’s optimistic, to say the least.

Do We Really Know What’s There?

Gut testing is at the forefront of Functional Medicine.  If you have consulted with me there is a high likelihood you have had a stool test done – whether to eliminate or exclude a gut bacteria issue from my line of enquiry, or to clarify precisely what we are dealing with digestively that may be having a systemic impact on your health.  The reason I do this is because through the Functional Medicine lens, gut health is a bedrock to systemic wellbeing.  (Hopefully this article will highlight the importance of the gut environment and how fundamental the gut biome is to your overall health.)

If you were my client up until approximately a month ago, the test we will have done was the Doctors’ Data Comprehensive Stool Analysis with Parasitology x 3: a 3-day test fully analysing the bacterial composition of your gut, alongside testing for yeasts, inflammation, short chain fatty acids, digestive markers, immune markers and any worrying signs of digestive disorders.

More recently I have been recommending the Diagnostic Solutions GI-MAP.  But realistically, I’d like to do multiple stool tests.  I do this because the different methodologies are fallible in different areas, and the testing science is improving all of the time, but is still at risk of being under- or over- specific.

Why so complicated?  Because testing bacteria through stool samples is not easy or simple.  It’s not like a blood test, it requires micro-analysing the composition of what is a very complex sample and then actually interpreting what is indicated by the end result.  What is present in our digestive systems goes through the transit of the gut and therefore doesn’t look the same once it’s outside of us, so analysing the internal environment based on what leaves it is much more difficult than it seems.

Both of the above tests use different science, and whilst the first is tried and tested it may be slightly insensitive and mis-state some of the data.  The GI-MAP is a newer kid on the block (or a newer use of an established technology) and therefore many practitioners are yet to trust its clinical utility.

The former assessed gut bacteria by how much can be ‘grown’ or ‘cultured’ outside of the human digestive tract, thereby giving an estimation of how well that particular bacteria are thriving in the gut of their host.  The GI-MAP checks for the DNA signature of microbes, whether alive or dead, indicating what has been living inside the host and at what level, thereby indicating the virulence of each particular strain.  There are positives and negatives to each approach – but mostly the key lies in the understanding and interpretation of the practitioner.

My gut feeling – pun intended – is that the GI-MAP is a real leap forward in the evaluation of stool samples for clinicians, but I do imagine that the reference ranges may be refined in years to come as clinical data is fed back to the laboratory currently operating the technology.

But I do want to make it clear that whilst these are broad insights into the ‘beneficial’, ‘commensal’ and ‘pathogenic’ bacteria, neither are formulated to give a literal picture of all of the bacteria present in your digestive system.  They are screening for what we have evidence to be ‘good’ and evidence as possibly ‘bad’.  They are not providing you with a printout of absolutely everything that is inside you.  So whilst we know a lot about how to sequence some data from human specimens, we don’t yet know how to identify everything we’re seeing.

And also, we don’t fully know what matters and what doesn’t – except in broad overview terms.  At present we’re only finding what we’re looking for because we know it’s important.  There is a lot that we don’t know and it could easily transpire that in the future we understand much, much more about something that we are not currently seeing because we don’t know to look for it.

Certain organisations such as The Human Microbiome Project or Ubiome are providing much more thorough lists of everything inside patients.  The only problem with the data gleaned in these tests is that it is practically unreadable and clinically un-useable.  These are vital for research purposes – it is these projects that will help us learn and discover more.  But they are not going to help me as a practitioner or you as a patient at this time.

Right now, analysing every single microbe in the human digestive tract is a little like sequencing the human genome.  (In fact, it’s worse – given that there are more than 9 million unique genes in the human gut bacterial community).  So – we know a lot about what’s there, a little bit but woefully not enough about what matters from what we know is there – and next to nothing about how all of the ‘what’s there’ talks to everything else there and then operates as an ecosystem within our digestive tract which communicates systemically throughout our bodies.

Do We Really Know What “Should” Be There?

One problem is that the majority of testing thus far has been done in mice or rat experiments.  Whilst this may be similar to the function of the human body, it is highly unlikely to provide identical results.

We have evidence into the role of certain ‘good’ bacteria such as lactobacillus and bifidobacteria – but only insofar as we know that the presence of these strains is found in those who are generally otherwise healthy.  There is some evidence to suggest that these strains are also linked to lower incidences of allergies and there are studies claiming that health outcomes can be altered by transplanting a ‘bad’ microbiota sample into an otherwise healthy individual – and vice versa.  This would seem to suggest that the microbiome has a causal effect on health, but in other situations it could be said that health compromises cause the dysregulation of the microbiome.

So much can disrupt the microbiome.  A single missed night of sleep can alter the microbiota, as can excessive stress.  More importantly, altering food intake, even slightly, will cause the microbiota to change and adapt.  It doesn’t take a lot to skew the population of bacteria within our digestive system.  So the question must therefore be asked: do people’s healthy practices transform the bacteria for the better, or do the healthy bacteria drive healthier practices and health outcomes?

That said, faecal matter transplants into ‘thin’ mice from obese mice have been shown to cause obesity in the mice which were previously thin.  And vice versa.  But this information is admittedly preliminary in humans – and other than specific clinical applications of using faecal matter transplants for C. Difficile infections, there is great inconclusiveness to this clinical approach.  If a patient changes nothing else about their life it is not yet clear whether their gut biome change will transform their health, or whether their lifestyle and nutritional intake will eventually cause their gut biome to revert back to the same bacterial dysbiosis as was present before.

We have seemingly identified that the presence of a specific type of bacteria – Firmicutes – is associated with leanness, whereas a higher prevalence of Bacteroidetes (a different type of bacteria) is associated with obesity and metabolic disease.  But firmicutes and bacteroides are types of bacteria – not specific bacteria in themselves.  So we sort of know what types might be beneficial, but this generalisation has been justly challenged because even when bacterial populations are played with to try and alter the firmicutes:bacteroidetes ratio, the results are not predictable nor consistent across study groups.

And lastly, if you take into account population studies and the difference in the microbiota of different populations dependent on their geographical location (and thereby, one would imagine, the foods that form the basis of their diet) you begin to realise that what bacteria should be in the digestive system largely depends upon what you’re asking your digestive system to digest.  The bacteria that feed off certain fibrous vegetables will flourish in a location where fibrous vegetables are the mainstay of the diet.  And the foodstuffs around you, such as fish in a Japanese example, are capable of seeding digestive systems with microbes associated with those foods – theoretically to enhance digestion of those foods, or perhaps for some other undetermined reason.

This does seem to suggest that our internal microbiota are what helps human beings be adaptive to their environment, almost like the malleability of the bacterial population is what enables us to be healthy given the availability of certain produce and other environmental factors in the specific location of the host.

Do We Really Know What “Shouldn’t” Be There?

I may see a very biased sample, but it is clear to me that the microbes may make us adapted and suited to the foodstuffs available in our environment but they can also make us very unhealthy and give rise to a whole panoply of systemic physical (and mental, and behavioural) issues.  However, it isn’t a hard line that we know every bacteria that is bad for us.

When it comes to ‘bad’ bacteria it is sometimes the quantity, rather than the particular bacteria itself which seems to be associated with it having pathogenic, disease-causing effects.  This means that low levels of certain bacteria are expected – but when that same particular strain becomes virulent we need to become concerned.

This is where the quantification element of the tests mentioned above becomes hugely important.  Low levels of even things that we think of as ‘bad’ (such as yeasts) are actually perfectly healthy and normal.  It is only when these strains start to take over that ‘dysbiosis’ occurs.

It is true that parasites can be symptomatic, with species such as Giardia, Blastocystis Hominis and Entamoeba Histolytica all contributing to the development of the symptoms of irritable bowel syndrome.  But not everyone is dealing with pathogenic and infectious diseases.  We are dealing with symptoms created by imbalances.

And here the word ‘dysbiosis’ is perfect in explaining the problem: there are imbalances of bacteria.  But where the line between balance and imbalance lies is often subjective.  I don’t mean in the eyes of practitioners.  I mean in the symptoms that present in patients.  A strain of bacteria that may be disease-causing and symptom-inducing in one patient may actually exist with absolutely no associated symptoms in others.

Further than this, patients can experience dramatic symptom improvement despite their test results showing that they have not yet returned to so-called ‘optimal’ levels of bacteria (especially in cases of Small Intestinal Bacterial Overgrowth – a condition where bacteria is present where it shouldn’t be in your digestive tract).  This may be because different patients have different tolerance for differing levels of dysbiosis.  So treatment based on test results can run the risk of over-treatment (and questions arise over whether a patient should continue treatment if they feel better).  And we don’t know whether a patient’s complete lack of certain strains is actually perfectly healthy for them.  But that said, stopping treatment after symptomatic improvement may just cause the issue to recur with more ease than had treatment been completed.

We simply don’t always know what we are aiming for.  We know general specifics – and we know the gut bacteria are massively implicated in a wide variety of diseases – but we don’t really know what is ‘healthy’ and what is ‘optimal’.  And whilst an argument could be made to say that all reference ranges on conventional laboratory testing has room for improvement, within the world of bacterial analysis it seems that the margins aren’t margins for error – they’re there because the goal posts can be moved totally depending on so many factors surrounding the health of the host, the environment, the genetics, the lifestyle etc. etc.

Do We Really Know How To (Or Whether We Can) Change What’s There?

The one thing that has been tested quite effectively is the different treatments for certain bacterial conditions within the gut.  The comparison between medical antibiotic products and more “natural” anti-microbials had perhaps surprising results.  A natural yeast, Saccharomyces Boulardii has been shown to be as effective as Metronidazole (an antibiotic) for the treatment of Blastocystis Hominis.  And herbal therapy is as effective as Rifaximin (a targeted antibiotic) in treating SIBO.

And yet the research about making demonstrable changes to the microbiome simply by supplementing with an over the counter probiotic is less clear.  To be validated as a probiotic, the product simply needs to contain the strains of the bacteria that it says it does – and be able to evidence that the strains it claims are in it do come through in the patients’ stool.  None of this actually says that any of that bacteria survives the passage through the stomach (an highly acidic environment) alive.  Nor does that data say that the bacterial strain being supplemented actually takes hold within the host’s digestive tract and stays there.

In fact, if a stool test is conducted shortly after a course of probiotics, exceptionally high levels of those supplemented strains can be found.  If a different probiotic takes its place the bacterial balance shifts entirely to reflect the new supplementation. This would indicate that the probiotic is hanging around within the tract, but not actually taking up ‘residence’, if you will, in the gut of the host.  In these cases it may be that the bacteria are around whilst the probiotics are being taken but rapidly disappear when supplementation is stopped.  This is therefore not an effective change to the inherent microbial balance of the patient.  So it may just be a very expensive waste of money.

And speaking of wastes of money, the literature has shown that those probiotic yoghurt products which promote their contents as the ‘good’ lactobacillus and bifidobacterium named above have no basis for their health claims as they cannot transform the health outcomes of those who take them.

So As A Clinician What Are My Microbiome Missives?

I know this article has been pretty pessimistic in tone.  As someone who has treated plenty of patients for bacterial dysbiosis conditions I do know that there is symptomatic relief and clinical validity to ridding the digestive system of pathogenic bacteria, overgrowths of yeast or fungus, and to clearing the bacteria from the small intestine.

However, I do not think that a clearance treatment is the end of the process.  Nor do I think that for most people there should be a regular need to clear pathogenic bacteria.

The microbiome relationship to its host is bi-directional.  We are regulated by the toxins, products and communication potential of the bacteria in our gut.  But we can also directly affect those bacteria and the ‘environment’ within our digestive tract.  We can alter how habitable it is for both ‘good’ and ‘bad’ bugs – and this isn’t just about the probiotics you take.

The major factor with gut health – whether focussing on the microbiome, or transit time, or nutrient absorption or immunological activity – is that the first defining factor of all of these health outcomes is the foodstuffs you choose to eat.

This is not some expensive, fancy, freeze-dried capsules of bacteria.  This is instead the food you put in your mouth frequently, daily, for life.  The first and most definitive way to completely transform the bacterial population within your gut (and therefore the toxins, short chain fatty acids, digestibility and signalling from your microbes) is through dietary changes.

Yes, it’s boring and yes, it’s arguably a little more difficult than popping pills, but nothing feeds the good bugs better than good foods.  And you have to eat anyway – you might as well feed the good bugs properly whilst you sate your hunger.

How to tweak intake and the impact of specific changes is perhaps beyond the scope of this article.  But realistically it’s not because it’s ridiculously simple.

It’s what you already know, because you’ve known it forever.  Whole foods, varieties of foods, plenty of vegetables, plenty of fibre, lots of colourful food (‘eat the rainbow’).  Cut back on the sugar, the toxins and the artificial processed rubbish.  It’s basically a universally beneficial approach for you as a human being, so it stands to reason that it’s going to be universally beneficial for the bugs that most benefit you.  And if you really want to optimise the internal environment to help your bacterial allies, you would also be wise to get adequate sleep, reduce stress and consume lots of prebiotic (i.e bacteria-feeding) and potentially fermented foods/drinks.  Because the relationship between gut and brain (and hence gut, the brain and the rest of your body) is bi-directional.

We are working in concert with the microbes with whom we exist symbiotically.  Excessive dysregulation of hormones and stress-related catecholamines can disrupt the balance everywhere and impact the microbiota.  Excessive consumption of toxic foodstuffs and/or inflammatory foods can disrupt the balance everywhere and impact the microbiota.

So at the end of this rundown on what is a phenomenally complex topic that is the subject of some of the latest and most hotly-anticipated biological and nutritional research… we still know what we need to.  Overall health is based on some fairly simple foundations, and therefore so is a healthy microbiome.

Eat real food, not too much, mostly plants.  (Thank you Michael Pollan…)


Leave a Reply

Your email address will not be published. Required fields are marked *