February 15th, 2021
1) Proton Pump Inhibitors, PPI, are linked to increased asthma risk
A new article in the JAMA Network noted that patients that used a proton pump inhibitor for gastro-esophageal reflux disease, GERD, had an almost two fold increased risk of developing asthma over time. This is an association study and not causative.
What do we know about the link between the two?
Asthma is well known to be a genetic disorder of immune dysregulation that has environmental triggers going all the way back to birth and early childhood.
Children that are born into natural environments, have healthy nutrition, avoid medications like antibiotics, avoid chemicals via inhalation or orally are at decreased risk for developing asthma. GERD, most of the time, is a lifestyle based disease that is caused by a standard American processed food diet coupled with chronic physical and mental stress and occasionally other risk factors. The only common link that is obvious is the pro inflammatory diet and intestinal microbiome dysfunction.
The fact that a patient that takes a PPI is at a higher risk to develop asthma is not surprising as this means that they have likely had unremitting chronic poor quality processed nourishment as their main source of calories. Asthma and GERD incidence are also tied to obesity and insulin resistance which are a direct result of chronic over nourishment with highly processed sugar fat food bombs.
There is some evidence that refluxed acid into the airway may also be a driver of airway irritation and inflammation changing local immune responses and lung microbiomes promoting reactive airways. In my mind, the primary driver of the dysfunction is the inflammatory based nutrition driving systemic immune dys-regulation that we see as airway hyperactivity and also gastrointestinal acid/lower esophageal sphincter irritation. It makes much more sense that the primary issue is higher up the food chain than just acid refluxed or genetic asthmatic causes. Immune changes continue to be the place where the rubber meets the road.
2) Evidence that the gut microbiome is linked to Major Depression has been emerging for years. Yang and colleagues publishing in Science Advances noted that over 300 samples of stool from depressed individuals and controls were compared finding that 47 specific bacteria and 50 metabolites were dramatically altered between groups. The specific metabolites, gamma amino butyrate, phenylalanine, tryptophan, that were found in the depressed individuals stool are known to cross into the blood stream affecting neurochemistry.
This data provides a mechanism for the "how" a shift in our intestinal microbes can alter our brain neurochemistry. If the volume and effect of our neurotransmitters are altered by the intestinal microflora, then we will see these changes as mental health disorders like depression.
Knowing these links, makes the microbiome a ground zero source for alteration when ameliorating a mental health disease. The pathway to healing was laid out a few weeks ago in this newsletter.
3) Autoimmune based Autism Spectrum Disorder or ASD - Maternal autoantibody induced autism accounts for roughly 18% of all autism cases to date. The study in Molecular Psychiatry from January 2021 found that through machine learning they could identify autoantibody biomarkers that were 100% associated with autism when found in a specific pattern. In other words, the mothers of autistic children with autoimmune antibodies targeted against certain proteins in the infant's developing brain in utero were noted in 100% of cases. This is a subset of autistic spectrum disorders only, however, this may actually be the front end of the wave that shows that all ASD may be autoimmune in a maternal to neonate transmission pattern.
The authors state, "This is the first report that uses machine learning subgroup discovery to identify with 100% accuracy MAR ASD-specific patterns as potential biomarkers of risk for a subset of up to 18% of ASD cases in this study population." (Ramirez-Celis et.al. 2021)
The mechanism seems to be autoimmune destruction of critical proteins in the developing mind of a baby. The proteins are collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2), guanine deaminase (GDA), lactate dehydrogenase A and B (LDHA, LDHB), stress-induced phosphoprotein-1 (STIP1), neuron-specific enolase (NSE)and Y-box binding protein 1 (YBOX).
Each one of these proteins has the following functions: For example, CRMP is involved in neuronal network formations. Antibodies against CRMP can alter neuronal formation and networking leading to dysfunctional brain activity. (Ohtani et. al. 2019)(Schmidt et. al. 2007) GDA is an enzyme involved in neuronal microtubule assembly. LDH A/B are involved in energy glycolysis pathways all over the body. Dysfunction in the neuron can affect neuronal growth and development. Every antibody that is found will likely be attacking a neuronal activity or a metabolic pathway that leads to the phenotype of the disease that we call autism spectrum disorder.
This data has profound implications for predicting future autism risk in a pre-pregnancy state. If we knew that a mother had these specific biomarkers in her blood stream, then her child would be orders of magnitude higher risk for developing autism spectrum disorders. There may be a future for pharmaceutical biological antibodies to bind and neutralize these antibodies to prevent autism. This is the first set of hopeful evidence in the prevention category.
For me, this data adds to the bigger and more obvious answer. As a society, we need to grapple with the reality that our collective lifestyle choices put us at risk for autoimmune antibody development via excessive and chronic inflammation and then downstream risk.
Read these three newsletters from 2018 and associated articles to better understand autoimmunity and how to prevent it.
Proal Current Opinions in Rheumatology
Colpitts J of Immunology