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

Host Microbe Super systems in Precision and Systems Medicine Professor Jeremy Nicholson

The Physics of the Cellular Membrane Mr Edward Kane

The Interface between Mitochondrial Research and Therapy for Chronic Fatigue Syndrome Dr Sarah Myhill

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.)

Autoimmune conditions

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

Dr Sarah Myhill

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:

Engine  Mitochondria
Fuel  Diet
Oxygen  Lungs
Accelerator pedal  Thyroid
Gear box  Adrenal
Service and repair  Sleep
Cleaning and Oil  Antioxidants
Catalytic converter  Detoxification
A driver  The brain

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:

  • Low levels of Adenosine triphosphate (ATP)
  • Low levels of magnesium
  • Low levels of vitamins such as Vitamin B3, essential for ATP synthesis
  • Low levels of Co-enzyme Q10
  • Low levels of Vitamin B12
  • Being blocked by a toxin

Dr Myhill's detox regime

  • A paleo, low carbohydrate diet
  • Micronutrient supplements
  • Treating a fermenting gut (itself a source of toxins)
  • Avoiding obvious toxins: cigarettes, alcohol, dental amalgam etc.
  • Chelation - usually oral
  • Heating regimes, especially for pesticides and Volatile Organic Compounds (VOCs) – sun, Epsom salts, infra red heating and regular saunas – all followed by washing to get rid of the toxins that will have been excreted via the skin.

A biochemical improvement will usually be evident before a clinical improvement in symptoms.

Other interesting points about mitochondria

  • A ketogenic diet (less than 60g of carbohydrates a day) provides excellent food for mitochondria.
  • A ketogenic diet is excellent for heart failure as the heart contains high levels of mitochondria.
  • Statins can knock out mitochondrial function.
  • The eye and the brain require proportionately very high energy levels to function. The brain is only 2% of the body's weight but uses 20% of its energy.
  • Vegetarian and vegan diets are a high risk factor for CFS.
  • Impaired delivery of energy as a result of mitochondrial malfunction will impact on all diseases.


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.


  • Each individual's bacteriological profile is affected by their method of birth.
  • An infant born by vaginal birth will have microbiota from its mother; and infant born by Caesarean section will acquire theirs from the doctors and nurses who delivered them and the surgical environment.
  • These differences will become less apparent over the years as their microbiota become more affected by the food that they eat.

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

  • Rat pups, separated from their mothers for only 3 hours per day, had reduced microbiome diversity as adults. They were also very anxious and pro-inflammatory – a marker for depression.
  • Human patients with depression also have a significantly less rich and less diverse microbiota than non-depressed patients.
  • If you transplant the microbiota of depressed humans into animals, you 'transplant' the depression both in terms of behaviour and biochemistry.
  • Pychobiotic bacteria (Lactobacillus rhamnosus and Bifidobacterium longum) travelling up the vagus nerve to reach the brain, appear to have a positive effect on both animal and human mental health – possibly by elevating levels of tryptophan or reducing levels of cortico steroids – or both.
  • In animal studies, animals fed bifido bacteria were much less anxious and had improved cognitive function (they worked out problems quicker).
  • In human studies of supplementation with bifidobacterium longum versus placebo, patients were not only less anxious but showed improvement in both memory and some objective tests.


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

  • If you raise animals in a germ free environment social behaviour, brain and memory function are all altered. Their stress levels are higher, they have larger amygdalas (the part of the brain primarily associated with memory, decision-making, and emotional reactions) and an especially high fear response. Their brains do not develop normally and they do not socialise.
  • Obese people have different microbiota which allow them to harvest extra calories from food. Modern psychotic drugs tend to drive obesity - maybe by changing the microbiota. But if you give psychotic drugs to germ free animals, they have no effect – so the obesity effect must come from the interaction of the psychotic drugs and the microbiome of those patients.

General points

  • If gut microbiota influence brain function and the stress response, could live psycho-therapeutics be use for mild depression?
  • Bacteria can obviously get into the bloodstream, but can they actually get into the brain? And if so, how? Via the vagus nerve or via a leaky gut or impaired tight junctions?
  • Could some of these bacteria making it through to the brain have side effects that are not beneficial?
  • Right now we have no idea of appropriate dosages.
  • How might an obese bacterial profile in a mother affect a child in a vaginal birth?


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

  • There are over 60 proteins and genes involved in creating the tight junctions between the cells of the gut wall which prevent a leaky gut.
  • Tight junctions are essential for gut integrity.
  • The protein zonulin is essential at the 'kiss point' to keep these junctions tight and impermeable.
  • Gluten compromises the efficiency of zonulin.

Processed foods and antibodies

  • A minimum of 63% of US calories come from processed foods.
  • Additives and 'manufacturing aids' (usually enzymes) used in food processing open tight junctions.
  • Significantly more antibodies are created by the body to processed than to unprocessed foods; wheat causes the generation of especially high numbers.
  • One of the most useful (to the food industry) manufacturing aids is Microbial Trasnglutamaise (MTG), a effective 'glue' which improves texture etc. (Because it is a manufacturing aid it does not need to be declared on a label.)
  • However, MTG cross links with gliadin, creating a whole raft of new antibodies which increase microbial permeability.
  • In mouse models, emulsifiers have been seen to lead to colitis, metabolic syndrome, obesity and liver dysfunction by dissolving the mucus in the gut lining.
  • Nano particles, used for drug delivery but also in high street foods, affect membranes, nuclei, mitochondria and damage mono and multi cell organisms.
  • Genetically manipulated bacteria from genetically modified plants can transfer to humans and eventually result in metabolic, functional and phenotypical changes – which can result in chronic autoimmune conditions.
  • A leaky gut allow these products through the tight junctions and into the blood stream.


  • 70% of rheumatoid arthritis patients have serious gut dysbiosis
  • Gut eco events nearly always lead to disease.
  • Ancient grain have 10% gluten; modern grains 80% and modern gluten is more toxic.


The Mosaic of autoimmunity
Why we develop Autoimmune Disease: the Microbiome and Metabolism

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.

June 2017

For the full conference see the BSEM website.


See here for many more conference reports on a wide range of subjects.

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