Gut Immune Body Brain Axis.
Dr Gundry:
Leaky Gut, gut microbiome and diet
Renowned Cardiovascular Surgeon who realised that all he was doing was treating the
symptoms so he studied the underlying causes.
The lining of the gut is one cell thick
As bacteria break down the gut that is when ageing starts
Ibuprofen or roundup disastrous the bacteria population
Skin is a mirror of the lining of the gut
Joints do not naturally wear out.
Animal model C Elegans as bacteria begin to break down the wall of the gut that is when
ageing starts
105 year old people have a diverse set of bugs identical to a healthy 30 year old. It is not
attacking the wall of the gut.
Ecermansia musinophilia. Lives in the mucous layer whose job is to trap lectins plant
proteins looking for sugar molecules and to protect the wall of the gut from harmful bacteria.
Ecermansia musinophilia eats mucus which in turn makes more mucus.
Metformin works by increasing mucous and this change in bacteria makes some people
have mild diarrhoea as the bacteria change.
If we damage this lining eg ibuprofen or food with roundup destroys the bacteria population
and gut lining.
Glyocosade an antibacterial damages Ecermansia Musinophilia even though it does not
directly affect human cells.
Antibiotics in food or direct prescription eg ladies who take low dose for UTI have a higher
incidence of heart disease.
Heart disease is an autoimmune disease starting in the gut.
Cholesterol is an innocent bystander which gets sucked into the inflamed wall of a blood
vessel.
Infants with heart transplants have coronary artery disease with pathology identical with
typical coronary artery disease.
Lectins which are a foreign protein which can stick to sugar molecules on the surface of
blood vessels are the cause of atherosclerosis and removing lectins reduces those markers.
Lectins are one of the plant defence systems. Sticky proteins that look for specific sugar
molecules to stick to which insights an inflammtory response.
Joints do not normally wear out. Usually you can find bacterial particles in the joint fluid of
arthritis
Because
Lectins broke down the wall of the gut. 65% of the immune system is behind the wall of the
gut because the gut is where the outside word gets through. A reason why we store fat in
the gut is to provide energy to the immune system. Similarly fat on the outside of
atherosclerotcic blood vessles correlates with the severity of inflammation.
Fat is not the cause . It is there because of the inflammation and the inflammation is there
due to the leaky gut.
The immune system responds to antigens on bacteria of viruses. Lectins have antigens with
cross reactivity with other proteins in the body. Eg thyroid.
Nightshade vegetables or peanuts
Lectins disrupt the microbiome and break up the lining of the gut allowing entry by lectins
and by bacteria or bacterial particles.
Hence if you inject a bacterial lipopolysaccharide into a person you can induce septic shock.
Alzheimers Parkinsons is neuroinflammation.
Most amyloid is produced by bacteria in the gut. Therefore 40 billion dollars invested in
antiamyloid drugs has been a waste because amyloid is produced by the amyloid producing
bacteria inthe gut fet by western diet. Then the amyloid has to get through the wall of the gut.
Once they get through the gut wall and goto the brain it will produce more amyloid.
Cholesterol and amyloid coexist in dementia in those with the apoE gene.
The apo E gene codes for a carrier molecule because it is less efficient at transporting
cholesterol. It cannot get out of the cell after it has been attracted by inflammation.
Faecal microbial transplant:
1970s broad spectrum antibiotics came out which made it much quicker to treat infections
but it also wiped out the gut bacteria. Normally 10000 species of bacteria.
Pseudomembranous colitis was caused by Clostridium Difficile over growing. Initial study
done from the faeces of medical students.
Faecal enemas treated the pseudomembranous colitis.
Meat with animals treated by antibiotics can also cause problems.
60% of faeces is bacteria
Oral microbiome and cloud of bacteria around us –Holobiome . This defines our personal
space.
Kissing is a human and ape characteristic. Exchanging oral microbiome. Bacteria decide
whether the other person's bacteria are compatible with them.
Women have a gut feeling because they are more capable of listening to their microbiome.
We inherit our microbiome from our mother. All of the mitochondria are involved with bacteria
inherited from our mother. Bacteria communicate to their ‘sisters ’ie the body’s mitochondria.
Autism: kids have a different microbiome than ‘normal’
The placental microbiome is important in educating the foetal immune system.
Oral faecal transplants for 6 weeks in autistic kids. Almost immediately 50% autism
symptoms reduced.
Ecermansia like tubers, mushrooms, -study in Asia find 90% reduction in Alzheimers with
two cups of mushrooms a week.
Inulin containing compounds eg chicory, radicchio, jerusalem artichoke.
Exercise women who exercise routinely from midlife have a 90% reduction in Alzheimers. In
those who get AD it happens 11 years later. Housework can be important part of exercise.
Meditation and yoga also changes the gut microbiome.
Lymph system in the brain in deep sleep -early in the sleep cycle-shrinks by 20% and these
bad proteins are squeezed out. You need a 3-4 hour window between sleep and dinner
because blood flow diverts to the gut.
Olive oil /walnuts / mediterranean low fat diet: first two groups improved memory after 5
years. 3rd group lost memory
Those with CVD had a 30% reduction in events, the low fat group continued CVS events.
Polyphenos in olive oil grow proteins
TMAO is made by gut bacteria primarily from animal protein especially choline eg egg yolk
and carnitine . TMAO damages blood vessels. Polyphenols in certain olive oil and red wine
balsamic vinegar that paralyse enzyme systems in the bacteria so they do not make TMAO.
However the logical error here is that eggs which are high in choline are not associated with
increased morbidity.
Vitamin D at least 5000 units a day . Almost all cancer patietns and autoimmune pateitns
have low vitamin D. HIgher your VItamin D the longer your telomere. Stem cells in the gut
are simulated by vitamin D.
VItamin C
Lectins are present in most plant foods but especially high in:

legumes, such as beans, lentils, peas, soybeans, and peanuts

nightshade vegetables, such as tomatoes and eggplant

dairy products, including milk

grains, such as barley, quinoa, and rice



The Roll of Inflammation in Depression and Fatigue
Frontiers In Immunology:
CH Lee 2019:


Immune system link to depression first noticed with immunotherapy eg INFa (which activates an inflammatory antiviral response) for Hepatitis C : associated with raised pro
inflammatory cytokines and depression and fatigue.
20% of patients treated with INFa developed depression which resolved on discontinuation
but also increased the risk of depression in future.
Also people with higher IL6 aged 9 were more likely to have depression aged 18 in a dose
dependent manner.
Innate immune system seems to be lower in depression eg NK cells and also less anti
inflammatory regulatory T cells whereas inflammatory monocytes are activated.
There is commonality in immune activation from autoimmune disorder such as multiple
sclerosis or immune reactions in sepsis.
Antidepressants reduce inflammation while a higher baseline level of inflammation predicts a
poorer treatment response.
People with depression have been shown to have higher inflammatory markers which can
be used to predict treatment efficacy and future recurrences of depression.
Elevated inflammatory markets eg TNFa after an MI disrupt the blood brain barrier causing
depression.
Inflammatory changes in the brain with raised TNFa in the hippocampus and striatum
precede development of depressive symptoms.
Neurogenesis is inhibited by the kynurenine pathway which is rescued by both inhibitors of
this pathway and traditional antidepressants.
TNFa also increases glutamate release causing exocytotic damage to surroundings
neurones.
Conditions associated with chronic immune activation such as asthma, atopy, diabetes m
MS, RhA, SLE are all associated with raised levels of depression eg 36% of asthma have
depression who also had higher TNFa than those who were not depressed. 75% in RhA
MS up to 50% risk of depression.
Acute inflammation with sepsis also causes depression and raises the risk of depression in
future which in animal models can be reduced by using steroid during the acute sepsis.
Antidepressants reduce inflammatory markers perhaps SNRI more effective than SSRI and
also ECT adds in return to normal of NK activity.
Directly reducing the immune response eg anti TNF a or Caspase Inhibitors have been
shown to reduce depression. Rituximab which is an antibody that targets and depletes B
cells in the treatment of RhA also reduces depression.
Aspirin can reduce depression but can also reduce the effect of an SSRI.