Getting to know the real you

Bacterial cells living within our bodies out number our ‘own’ cells – so just how seriously should we take the health of these internal aliens? Very, says Glenn Taylor; for their well-being is intimately connected to our own. 

In this somewhat sterile age, we often overlook the fact that the human body is mostly made of bacteria. In fact, bacterial cells living in every one of us out number our own cells by 10 to 1. What’s more, these bacteria collectively possess 100 fold more genes than the human genome. This collection of bacterial genes is known as the microbiome. As humans we have evolved with bacteria and other microbes and the interaction between these microorganisms and our bodies is, as the scientific world is at last discovering, integral to health.

It is now becoming all too clear that many aspects of modern life, including birth practises, environment, diet, lifestyle and drugs, are affecting our microbiomes and contributing to disease. Babies are born with virtually sterile colons and become ‘inoculated’ with a mixture of microorganisms from the mother’s vaginal and anal canals during birth. These are soon joined by bacteria from the environment, transferred from everyone and everything that the infant touches. The practise of breastfeeding provides yet more microbes, along with the perfect food to nourish this growing ecosystem.

The early years are a critical time for the development of the microbiota within the gut, disruption of which can have long term health consequences, including increased risk of asthma, allergies and even obesity¹,². In tests on germ free rodent models, the absence of the microbiota during the first few weeks of life has a devastating impact on development, particularly of the immune system³. Our microbiome continues to evolve throughout our lives. The food we eat, how stressed we are and our level of physical activity are all examples of factors that can modify our microbiomes. While we cannot change our own genes, we can, through healthy lifestyle choices and interventions such as microbiota transplantation, modify our microbiome, and through doing so, impact our health.

Our Palaeolithic ancestors would have dug up roots, brushed off the large lumps of dirt and eaten the food raw, complete with soil-based-organisms. Fruit would have been picked and eaten straight from trees, complete with a bloom of natural yeasts and water would have been drunk straight from natural streams. They would have handled their meat, coming into contact with all the microbes that the animals were carrying. So, in short, our bodies have evolved to live in constant contact with a rich melting pot of naturally occurring microorganisms, but today we sanitise everything…countertops, floors, clothes and even ourselves, and our kids don’t play in the dirt anymore.

Our food is also affected; everything that comes in a packet or tin has been processed with the intention of preventing the growth of microbes in order to make it keep longer. This processed, convenience diet has lost a lot of its natural diversity. The vast proportion of what we eat now is made from just a few ingredients: refined wheat flour, refined sugar and vegetable oils. Our modern diet is also notoriously low in fibre, which most species of bacteria in our guts require to thrive. The overly sanitised environment combined with poor diet makes it very difficult for a healthy, diverse microbiota to develop and thrive, but to make matters worse, we are actively destroying it.

The overuse of antibiotics is the prime culprit. Antibiotics don’t just kill the pathogenic microorganism, they kill a lot of the ‘friendly’ species too and once a species has been wiped out, even the most healthy diet and perfect lifestyle can’t get it back. Of course, the modern increase in sanitation and hygiene has saved countless lives and dramatically reduced the burden of infectious disease. However, the modern microbiome, with its reduced diversity may be less stable and thus, less able to ‘bounce back’ to normal health after an infection.

This is well illustrated by the prevalence of ‘post-infectious’ Irritable Bowel Syndrome (IBS). The risk of developing IBS following an episode of acute gastroenteritis increases by a whopping seven fold, most likely caused by lasting changes in the microbiota and the knock on effect of this on host physiology. Seventy per cent of the body’s immune tissue is located in the gut? so it is no surprise that disruption to the bacterial ecosystem (dysbiosis) can result in inflammation and disease states. The lumen of the gastrointestinal tract is technically outside the body, with the gut wall providing a barrier between the inside of the body and outside world. If the gut is healthy, the barrier permeability is highly selective, letting fully digested food molecules pass into the blood stream, while keeping unwanted elements, including bacteria and partially digested food, out. If the barrier becomes compromised, it may result in increased translocation of bacteria and other debris into the blood stream, producing a systemic inflammatory state.

Many disease states are associated with dysbiosis, systemic inflammation and impaired gut barrier integrity including gut conditions such as, inflammatory bowel disease and IBS, allergies, asthma, obesity, diabetes and even neurological conditions such as multiple sclerosis (MS) – the list is endless?-?. These relationships are currently poorly understood and it is often unclear whether the dysbiosis is a cause or consequence of the disease, however even in cases where dysbiosis is present, correcting it can often ameliorate at least some of the symptoms.  While probiotics and prebiotics, combined with a healthy lifestyle can go some way to improve microbiome health, they cannot restore the lost diversity.

Bacterial species do not like to live alone. They co-exist with other bacteria of different species, so it is no surprise that probiotics, which usually contain just a few strains, struggle to colonise the gut. In addition, probiotic bacterial strains have usually adapted to the lab environment in which they are cultured, losing many of the attributes required to colonise the gut. Although their effects are largely transient, they can infer benefits, for example through immunomodulation or temporary modification of the gut environment. Prebiotic fibres selectively feed beneficial bacteria, increasing their numbers. While this is beneficial, pre-biotics can only feed species that are already present and cannot increase diversity. In essence, Faecal Microbiota Transplant (FMT) is the only way to restore microbial diversity that has been lost due to antibiotics use, disease or the modern environment.

FMT involves the transplantation of normal gut bacteria, harvested from a healthy donor, into the gut of a patient whose own microbiome has become disrupted. The donors must undergo a rigorous screening process to ensure that they live healthily, and have had minimal antibiotic exposure. They also undergo regular, comprehensive, blood & stool analysis to eliminate the possibility of passing on an infectious disease to the patient. The donated faecal material is ultra-filtered to remove waste products leaving just the concentrated bacteria behind.

The preparation of an implant is completed within hours so the bacteria have little time to mutate or adapt to the exogenous environment, retaining all the features they require to colonise the gut. By implanting the whole ecosystem of faecal bacteria, the relationships between bacterial species remains intact, helping them thrive and colonise. In the simplest circumstances, for example, dysbiosis due to recent antibiotic use, the primary pathology is disruption of the microbiota and a lack of microbial diversity. In such cases, a few treatments are often enough to restore the ecosystem to a healthy state and symptoms improve almost immediately.

The best illustration of this is Clostridium Difficile infection. It is estimated that around 3% of the population carry C. Diff without disease, but when extensive antibiotic use decimates the healthy flora, it allows C. Diff to multiply. Once a critical concentration is reached, the normally harmless C. Diff will cause disease. Treatment with FMT rapidly restores the healthy bacterial ecosystem and suppressing the ability of C. Diff to express pathogenicity. With cure rates well over 90%, this is clearly the only sensible treatment, yet currently it is only accepted in refractory cases, where treatment with yet more antibiotics has failed.

In most cases, acute gastroenteritis (food poisoning, traveller’s diarrhoea) or antibiotic treatment will have some degree of lasting effect on the microbiome, the consequences of which are largely unknown. FMT is an ideal way to return the gut to a healthy state, rapidly treating or even preventing any symptoms which may develop.  A novel concept in this area is that of autologous FMT. For those anticipating a scenario that may disrupt their microbiome, such as chemotherapy, an FMT implant of their own can be prepared before the procedure and then frozen for later use.

It is not only diseases with clear bacterial pathologies that respond to FMT. Recent studies have shown promise in the treatment of insulin resistance? and inflammatory bowel disease, with a recent RCT confirming its efficacy in the treatment of ulcerative colitis?.  In more complex conditions, repeated treatment is often required, perhaps to give the immune system time to respond to and be modified by the new bacteria – and to give the body time to recover. Research into FMT is very active, with over 100 clinical trials currently underway, treating many different conditions, including inflammatory bowel disease, liver disease, diabetes and obesity.

Results so far are certainly promising, but only time will tell the true implications of this revolutionary treatment.

The author:

Glenn Taylor is Director of Science at the Taymount Clinic.

www.taymount.com

References

1. Arrieta, M.C., et al., The intestinal microbiome in early life: health and disease. Front Immunol, 2014. 5: p. 427. 2. Legatzki, A., B. Rosler, and E. von Mutius, Microbiome diversity and asthma and allergy risk. Curr Allergy Asthma Rep, 2014. 14(10): p. 466. 3. Round, J.L. and S.K. Mazmanian, The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol, 2009. 9(5): p. 313-23. 4. Vighi, G., et al., Allergy and the gastrointestinal system. Clin Exp Immunol, 2008. 153 Suppl 1: p. 3-6. 5. Joscelyn, J. and L.H. Kasper, Digesting the emerging role for the gut microbiome in central nervous system demyelination. Mult Scler, 2014. 20(12): p. 1553-9. 6. Walker, J., et al., High prevalence of abnormal gastrointestinal permeability in moderate-severe asthma. Clin Invest Med, 2014. 37(2): p. E53-7. 7. Bischoff, S.C., et al., Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol, 2014. 14: p. 189. 8. Vrieze, A., et al., Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 2012. 143(4): p. 913-6.e7. 9. Moayyedi, P., et al., Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology, 2015. 149(1): p. 102-109 e6.