BSEM – Systems Medicine: Bridging the Gap between Science and Clinical Practice
Some notes on the presentations – Michelle Berriedale-Johnson
Please click on the links for the individual presentations.
Tribute to the late Dr John Mansfield Dr Damien Downing
The Physics of the Cellular Membrane Mr Edward Kane
Psychobiotics: A novel therapy in Psychiatry Dr Ted Dinan
Food Additives, symbiosis and intestinal impermeability: potential inducers of autoimmunity Professor Aaron Lerner
The Mosaic of autoimmunity. Why we develop Autoimmune Disease: the Microbiome and Metabolism Professor Yehuda Shoenfeld
A tribute to the late Dr John Mansfield
Dr Damien Downing – President of the BSEM
The day started with a short tribute to the late Dr John Mansfield, one of the three founding members of the BSEM.
Inspired by the work of Dr Richard Mackarness, who pioneered the idea that both physical and mental illness could be caused by food sensitivity, he developed a desensitisation protocol through interdermal provocation and neutralisation at his Surrey practice at the Burghwood Clinic.
Dr Mansfield was the active organiser of numerous scientific meetings and conferences while training many doctors in ecological medicine. He wrote six books relating mainly to food sensitivity and dysbiosis; they included dietary approaches to the management of migraine, arthritis and asthma.
'His work lives on through his books, his students and the ongoing services of the Burghwood Clinic.'
Host Microbe Super systems in Precision and Systems Medicine
Professor Jeremy Nicholson, Professor of Biological Chemistry, Director of the MRC-NIHR National Phenome Centre, Director of the Centre for Gut and Digestive Health, Imperial College
Precision medicine is all about monitoring and control and it needs to start pre-birth.
Illness arises from an interaction between genes and environment; knowing about the genes alone is not helpful as illness is nearly always caused by an environmental interaction on those genes.
The microbiome is the the body's interface and it is totally specific to each area of the body – each tooth has its own microbiome, for example.
We used to die mainly from infections and although, with the development of antibiotic resistant bacteria, we risk returning to that, at the moment the main causes of death in the Western world are conditions such as diabetes and obesity. This change in cause of death cannot be genetic – it has happened for too quickly for the genes to have change.
So could it have been caused by a significant change in our microbiomes?
The microbiome takes three years to develop in infants. Those first years are critical to the subsequent health of each child and healthy development can very easily be derailed by a host of environmental factors. (An antibiotic given before the age of one, for example, can predispose a teenager to obesity.)
Throughout life the microbiome remains very responsive to diet. (In an experiment in which an African group, eating mainly fruits, vegetables and pulses, 'swopped diets' with an Afro-American group eating a standard burger and soda US diet, the microbiomes of each group had changed dramatically over the course of two weeks.)
The gut microbiome is a fundamental regulator for the immune system and so disorders of the gut microbiome are a crucial element in all autoimmune conditions.
The host genome is constantly interacting with, and being changed by, the chemical factory that is the microbiome – an endless series of enzyme pathways that create a series of axes for further interaction.
Interventions which seem simple – such as the removal of the colon – may have dramatic microbial outcomes of which we are not even aware. Historically microbiology was genomic but that is no longer enough, we need to be looking at the related bacteria.
National Phenome Centre
Population screening, linked to chemical and outcome data is crucial to further understanding of the biome. The National Phenome Centre at Imperial College is now the world's largest collector of such data.
(The laboratory was originally set up at the cost of £25 million to test for drug cheats at the London Olympics in 2012. During the course of the games they identified 12 - at a cost of fractionally over £2 million per cheat!!)
Population wide data will allow the assessment of dietary components in relation to the microbiome and to disease outcomes.
It is now becoming possible, using spectroscopoy and spectrometry, to deconstruct bacteria into their component parts – proteins, molecules etc – and thus to understand them better. It may be possible to use this knowledge to intervene therapeutically, and even, possibly, to design therapeutic bacteria although there are many dangers inherent in any such attempts.
Pharmaceutical interventions (not just antibiotics) can have dramatic effects on the microbiome. Better data on these outcomes would enable a much better understanding of both how drugs affect the bacteria and how the bacteria could impact on the drugs thereby changing their effect on the body. You could for example use pre-intervention data to dictate the pharmaceutical intervention making it safer and more effective.
However, the pharmaceutical industry has so far shown little interest in the microbiome and remain focused on the genome.
Cancer patients have very poor bacterial diversity in their microbiomes. Is this relevant?
In this context probiotics are not helpful; prebiotics, which feed the existing good bacteria, tend to be more effective.
Genes may be far less relevant in autism than has been thought.
Seventy per cent of autistic children have severe gastrointestinal disorders and many have overgrowths of bizarre clostridial species.
Could early microbial disruption in the gut have affected neurological development in these children? And could where they are on the spectrum be related to when in infancy this adverse event occurred?
Autism is not just a neurological defect. Most autistics also have other severe microbiological and chemical abnormalities – such as, for example, serious sulphate depletion which can adversely affect many processes within the body.
Dietary interventions seem to be by far the most effective management strategies – as illustrated by a US study looking at 100 interventions. Of the 20 most successful, 19 were dietary and the 20th was an anti-fungal.
Boys versus girls
It increasingly looks as though this may be a completely different condition in boys and girls. To be noted: early behavioural interventions are quite successful in boys but are rarely so in girls. And the number of autistic girls is increasing significantly.
The Physics of the Cellular Membrane
Mr Edward Kane, CEO of BodyBio
Ed Kane has spent a long life studying fats (phospholipid biochemistry and especially neuro-metabolism and lipid chemistry) while running a series of highly successful businesses culminating in BodyBio, a biomedical data management company providing medical reports to physicians worldwide.
The crucial fats he sees as being the tiny (5 nanometre) membrane phospholipid building blocks which protect all systems in the body. Because they are either hydrophobic or hydrophylic (hate or love water) they hold everything in balance.
He believes most illnesses stem from the poor treatment of fats (mainly through over-heating) although getting the balance of fats right is also crucial. He agrees with the 4:1 ratio, four parts of omega 6 linoleic acid (LA) and one part of omega 3 a-linolenic acid (ALA) proposed by Professor Yehuda. See this article in the BodyBio newsletter.
The Interface between Mitochondrial Research and Therapy for Chronic Fatigue Syndrome
Diagnosis is all about detective work to establish the mechanisms and identify which are malfunctioning. She referred to her analogy of the body as the engine in a car needing a whole range of inputs apart from petrol to make it work:
If the body is a car…to get it to go you need:
If any of them malfunction seriously, the car won't go – and nor will your body!
Chronic fatigue syndrome (CFS) and mitochondria
CFS occurs when the body's energy supply cannot keep up with its needs. It is the mitochondria which generate that energy for all body functions and so are relevant in all disease states.
There is a very direct correlation between mitochondrial function and the experience of fatigue in CFS so being able to assess mitochondrial function (thanks to the tests devised by Dr John McLaren Howard at Acumen Laboratory) is extremely helpful in diagnosis. The tests are also greatly valued patients as they validate a diagnosis of CFS which is otherwise so often dismissed as a non-illness.
However, while they are invaluable for diagnosing CFS these tests are not helpful for ME as many other elements are involved in ME.
But why do mitochondria malfunction?
Are they in some way deficient or is their activity blocked or inhibited?
There could be many reasons, many of which should be identifiable through a mitochondrial test. They could include:
Dr Myhill's detox regime
A biochemical improvement will usually be evident before a clinical improvement in symptoms.
Other interesting points about mitochondria
Psychobiotics: A novel therapy in Psychiatry
Professor Ted Dinan – Professor of Psychiatry, University of Cork
Humans co-evolved with bacteria of which there are 1.5 kilos in the adult gut – many more bacteria than we have genes.
The microbiota and the brain
Microbiota in the gut produce most of the neurotransmitters that operate in the brain.
Communication between the gut and the brain would appear to take place via short chain fatty acids travelling up the vagus nerve which runs from the colon right into the brain.
Animal and human studies
We do not digest pre-biotics but they do promote the growth of probiotics and beneficial bacteria in the gut. It appears that they may also reduce levels of anxiety – so is this as result of them promoting the growth of good bacteria?
Germ free animals
Food Additives, dysbiosis and intestinal impermeability: potential inducers of autoimmunity
Professor Aaron Lerner - B. Rappaport School of Medicine, Techion-Israel Institute of Technology, Haifa
Dysbiosis, leaky gut and tight junctions
Processed foods and antibodies
The Mosaic of autoimmunity
Professor Yehuda Shoenfeld - Director of the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center at the Sackler Faculty of Medicine at Tel-Aviv University.
'In autoimmunity, everything is the microbiome until proven otherwise.'
One in every two Americans suffers from one of over 80 autoimmune conditions
Why has there been such a massive increase in autoimmune disease over the last 50 years?
In all autoimmune disease there is always a genetic factor – a genetic predisposition – hormones are very important. But, an environmental trigger (infection, drugs, vaccinations etc) is needed for disease to occur.
An inherently strong immune system may be able to withstand an environmental assault – or, it may be pushed to react more strongly thereby creating an autoimmune condition.
Geography appears to be important
The further from the equator the higher the incidence of autoimmune disease. Could this mean that a lack of UV light and vitamin D could be relevant in developing autoimmune conditions?
Where humans carry helminths in their guts, there appears to be no incidence of autoimmune disease. So do helminths work by modulating the microbiome?
However, if other pro-autoimmune disease factors are too strong they will overpower the protective effect of the helminths.
For the full conference see the BSEM website.