This is a report from December 2016 American Academy of Anti-Aging Medicine (A 4m) annual meeting: David Perlmutter, MD ‘s presentation.  The materials are taken from his lecture and his latest book, The Brain Maker


Chronic diseases for which there are inadequate treatments are increasing in the Western world.    While genetics play a role in diseases, genetics and DNA are not our destiny.   Diet and life style choices can change DNA through epigenetics.  Ninety-nine percent of our DNA is microbial DNA which is in the gut.  Hence, the gut has a large role in genetic expression, and many of these diseases can start in the gut.



Inflammation is major contributing cause to most diseases.  Inflammation leads to conditions such as obesity, diabetes, cancer, strokes, autism, depression, ADHD, asthma, arthritis, coronary artery disease, multiple sclerosis, and Parkinson’s and Alzheimer’s disease. Chronic inflammation leads to a decrease in hippocampal neurogenesis, brain inflammation and disease and ultimately cognitive decline.  Chronic intestinal inflammation and proinflammatory cytokines lead to the same end.




The Gut

The gut has many roles. It

·     Aids in digestion and the absorption of nutrients

·     Provides a physical barrier against potential invaders such as bad bacteria, harmful viruses and injurious parasites.

·     Provides the first line of defense against many toxins

·     Serves as the biggest immune system organ

·     Produce and release important enzymes and chemicals for the brain.

·     Helps handle stress through the flora’s effects on your endocrine-hormonal-system.


Microbial Diversity

It is important that the gut bacteria (or microbiome) be balanced and well diversified.  Reduced microbiome diversity has been linked to increased gut permeability, autoimmune, metabolic and inflammatory diseases, diabetes (types 1 and 2), obesity, Alzheimer’s, MS, autism, colorectal cancer, inflammatory bowel disease



Leaky Gut

When the gut microbiota is altered or disrupted, it is referred to as “dysbiosis,” which results in the gut becoming inflamed and permeable (“leaky gut”).  A leaky gut allows substances to pass through the walls of the gut into the blood stream.   This leads to inflammation and oxidative stress – triggers for chronic diseases.   A permeable gut also can start an autoimmune response because antibodies are formed against the food proteins that pass through the wall of the gut.  


LPS (Lipopolysaccharide, an endotoxin) is a major component of cell membrane of Gram (-) bacteria.  It protects bacteria from being digested by the bile salts of the gall bladder.  Normally the intestinal tight junctions prevent the LPS from entering the blood stream.  However, when the gut becomes permeable and LPS crosses into the blood stream, LPS turns on inflammation pathways and has been linked to major depressive disorder, sporatic ALS, early ALS, Alzheimer’s Disease and autism.  1   Decreasing LPS can decrease inflammation which can increase the SCFA butyrate which is a beneficial bacteria.




Two thirds of people in the US are either obese or overweight.   Obesity can result from the composition of the microbiome and from a leaky gut. 2 The microbiome transferred from a thin twin mouse to more obese twin results in a weight change in the recipient twin. 


Obesity is associated with inflammation, decreased hippocampal volume and cognitive decline.  3  A larger waist to hip ratio may lead to neurodegenerative, vascular or metabolic processes that affect brain structures underlying cognitive decline and dementia.  4




The costs for treating dementia patients alone is approximately $200 billion per year in the US.  Two key mechanisms that lead to brain degeneration are chronic inflammation and the action of free radicals.


With gut leakage, inflammation and autoimmune triggers become systemic and can lead to neuro inflammation in the brain.  This activates the cerebral microglial cells which set off a cascade leading to inflammation of the brain.   Unlike immunity cells in the body which can be turned off by T regulatory cells, the microglial cells in the brain cannot be turned off


The gut brain axis or brain gut axis is a bi-directional communication system with pathways encompassing enteric nervous system and the vagus nerve.  A large part of the brains output goes to the Vagal nerve.  One of the first signs of the brain not firing well is poor vagal activity which manifests as decreased pancreatic enzyme secretion, poor gallbladder function and poor gut function over all  (Chris Kresser podcast)


Differences in microbial diversity can heal explain patterns of age-adjusted Alzheimer’s rates between countries.     Increasing microbiota diversity was found to be inversely related to the incidence of age-adjusted Alzheimer’s Disease.  Alzheimer’s disease incidence decreased with increasing parasitic stress


Mental Illness

More than 26 percent of the population suffers from a diagnosable mental disorder.  The microbiome plays an instrumental if not causative factor in mental disorders.      


Depression occurs in a quarter of women in their forties and fifties.  Autoimmune diseases, infections and poor diets are risk factors for depression.  Persons on a Mediterranean diets which have anti inflammatory fats enjoy significantly lower rates of depression.   SSRIs  may improve symptoms by increasing neurogenesis in the hippocampus


More than 11 % of children aged four to seventeen are diagnosed with ADHD.  Two thirds are medicated.  More than 10,000 toddlers (two- and three-year-olds) are now being medicated.  Breast fed infants are less likely to be diagnosed with ADHD in the future.



Protective Influences for the Microbiome

There are many factors that promote a healthy diverse microbiome.   A natural vaginal birth is important because it allows the child exposure to the microbiota of the mother and gives the child a health microbiome start.  Breast feeding supports the microbiome as well.  


 The microbiome has changed over time.  By examining dental calculus (hardened dental plaque caused by the precipitation of minerals) containing mineralized bacteria, changes were found.   5


Diet has a dominant role in shaping the gut microbiota.  Rural children in Burkina Faso had more healthy fecal microbiota that European children.  The African children had more short chain fatty acids in their feces compared to the European children.  Dr. Perlmutter hypothesizes that the reduction in micobiota richness found in European children is related to the high levels of sugar, animal fat and calorie-dense foods consumed in industrialized countries.   6


 A high fiber diet, consumption of probiotics (such as kimchi, sauerkraut, yogurt, kefir, kombucha)

and prebiotics (jicama, dandelion greens, garlic, chickory root, Jerusalem artichoke) help diversify the microbiome.


Negative influences on the mcriobiome

Events that threaten microbial diversity include antibiotics, birth by cesarian section, medications, water treatment, diet, hormone therapy.  These lead to inflammation. a postulated causative factor in Alzheimer’s disease, Parkinson’s disease, autism, multiple sclerosis, stroke, depression, ADHD

Other factors that hurt microbiome include obesity, the western diet, hygiene, stress, and pathogenic bacteria, gliadin, high fructose corn syrup, environmental chemicals, insecticides, and genetically modified foods. 


Fructose, which is represents 42 percent of all caloric sweeteners in the US.   High fructose corn syryp increases circulating LPS by 40 % and has a detrimental effect on the microbiome. 



Glyphosate (roundup) (for GMO products)

Glyphosate (roundup) is used in more than 750 different products for agriculture, forestry, urban and home applications.    Glyphosate is considered “probably carcinogenic to humans”.  7   It changes the microbiome and impairs the  detoxification pathways (cycochrome P450 pathways).  It compromises vitamin D 3 activation, and it chelates iron, cobalt, molybdenum and copper  It also depletes tryptophan, tyrosine, methionine and selenomethionine.



Gliaden (a component of gluten)

Intestinal exposure to gliadin, a component of gluten,  induces an increase in intestinal permeability in all individuals, regardless of whether or not they have celiac disease.





Certain Medications



Antibiotics   Any exposure to antibiotics increases the risk for diabetes type 2 ( which can increase the risk for Alzheimer’s Disease.)   Narrow spectrum antibiotics have more adverse effects than broad spectrum antibiotics.  Seventy percent of antibiotics are given to animals to make them fat.


The association between the increasing cumulative days of antibiotic use and increasing cumulative number of antibiotic prescriptions were associated with increased risk of diabetes type 2, incident breast cancer and death due to breast cancer.  All classes of antibiotics were associated with increased risk.


While antibiotic therapy has dramatically reduced infectious disease burdens worldwide it also acts as weapons of “mass microbial disruption. “  

Antibiotics have effects on intestinal microflora and immune and inflammatory responses. For example, antibiotic use may increase the risk of breast cancer by decreasing phytochemical metabolism by intestinal microflora.  There is mounting evidence from rodent models suggesting that antibiotics may drive changes in insulin sensitivity, glucose tolerance, lipid deposition and energy harvesting potential by altering the gut microbiota composition.  8


Proton Pump Inhibitors (Antacids)

Potential Adverse Effects of Proton Pump Inhibitors in the elderly include clostridium difficile infections, hip fractures, community acquired pneumonia, vitamin b 12 deficiency, allergic reactions.  PPIs also increase the risk of Alzheimer’s disease by 44 %   9 and also increase the risk of heart attacks and cardiovascular mortality.  10





Statin users had 46 % increased risk of type 2 diabetes.

Insulin sensitivity decreased 24 % and insulin secretion decreased 12 %.  Diabetes increases the risk of Alzheimer’s Disease.  The highest risk was for statin users whose initial blood sugars were the lowest (<99) at the beginning of the study.  11





Regulating the microbiome can help with virtually any degenerative of inflammatory condition.  This includes such conditions such as asthma autism, chronic fatigue, mood disorders, diabetes and sugar craving, memory problems frequent colds or infections, insomnia, hypertension, atherosclerosis, chronic yeast problems gum disease, Tourette syndrome, extreme menstrual and menopausal symptoms.   Decreasing gut dysbiosis may attenuate neuroinflammation and treatment for obesity related cognitive impairment


To turn on the good genes which will keep inflammation in check

·     Healthy organic diet

o  Low carbs, gluten free diet

o  Enriched with prebiotic fiber and fermented foods

o  Probiotics


Probiotics                        prebiotics

Kimchi                                jicama

Sauerkraut                       dandelion greens

Yogurt                               garlic

Kefir                                  chickory root

Kombucha                      Jerusalem artichoke

DHA change genetics


·     maintain healthy blood sugar levels

·     aerobic activities increase microbial diversity and nerve growth factor  which can generate new neurons. Twenty percent of gut diversity can be explained by peak oxygen level.  12




For more information, an interview with Dr. Perlmutter is on Occupy Health on Voice America found under Susan Downs






1,  Zhang R et al. J Neuroimmunol. 2009. (206) 121-4.


2.  2.  Obesity and gut’s dysbiosis promote neuroinflammation, cognitive impairment and vulnerability to Alzheimer’s disease: New Directions and Therapeutic Implications. J Mol Genet Med 2014, S1.


 3.  Daulatzai MA. Obeisty and Gut’s dysbiosis promote neruoinflammation, cognitive impairment and vulnerability to Alzheimer’s disease: new directions and therapeutic implications. J Mol Genet Med 2014, S1.


4.  Jagust W, Harvey D, Mungas, et al.  Central Obesity and the Aging Brain. Arch Neurol. 2005:62; 1545-1548.


5.  Warinner C, Speller C, Collins J et al. Ancient human microbiomes. J Human Evolution 79(2015) 125-136.


6.  De Filippo C, Cavalieri D, Di Paola M. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.  PNAS, June 30, 2010.




7.  Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. The Lancet, March 20, 2015.


8. Mikelsen KH, Knop FK, Forst M et al. Use of antibiotics and risk of type 2 diabetes: a population-based case-control study. J CLin Endocrinol Metab 100: 3633-3640, 2015.


9.  Association of proton pump inhibitors with risk of dementia.  JAMA Neurology. February 15, 2016.


10.  Shah NH, LePendu P, Bauer-Mehren A. Proton Pump Inhibitor Usage and the Risk of myocardial Infarction in the general population. PLOS ONE, June 10, 2015.


11.  Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. Diabetologica 2015 May: 58:1109.


12.  Estaki M, Piether J, Baumeister P et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome. August 8, 2016.4:42.