Episode #226: Microglial Activation in Chronic Illness with Dr. Jonathan Streit, DC, CPN, IFMCP
In a Nutshell
Microglial activation, the brain's resident immune cells shifting from protective M2 (nutrient-delivering, pruning) to destructive M1 (inflammatory, cytokine-secreting) states, drives chronic neuroinflammation in Lyme, Epstein-Barr, mold, trauma, and conditions like Alzheimer's, autism, PANS/PANDAS, and autoimmunity, persisting even after triggers subside. Key triggers include infections, head trauma, emotional stress, mycotoxins, EMFs, high glutamate/LPS, and gut dysbiosis; symptoms manifest as brain fog, pain, anxiety, and cognitive decline. Top interventions: calm M1-to-M2 shift with luteolin, LDN, sulforaphane, PEA, honokiol, butyrate, nicotine, fish oil, apigenin, peptides (BPC-157), SPARK diet, limbic retraining, EMF mitigation, hydrogen therapy, 40Hz light/sound, sleep optimization, and terrain detox—detailed in *Silent Spark*.
These notes were generated by AI and may contain inaccuracies.
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Hello everyone and welcome to episode 226 of the Better Health Guy blogcast series. Today's guest is Dr. Jonathan Stright, and the topic of the show is microglial activation in chronic illness. Dr. Jonathan Stright is a functional and European biological medicine practitioner. He's dedicated his professional life to helping patients with complex chronic illnesses. His passion for this type of work grew from walking with his wife through her own battle with Epstein-Barr and Lyme disease. Since then, Dr. Stright has focused his career on applying and advancing these approaches to address the deeper roots surrounding chronic illness. He's the co-founder of the Institute for Restorative Health where he and his team use the biorestorative method, a comprehensive approach that blends European biological medicine, functional medicine, neurology, nutrition, and terrain-based healing principles. Dr. Stright has trained with internationally recognized leaders in healthcare, completed postdoctoral work through the American Institute of Postural Neurology and teaches pathology and functional medicine for the University of Integrative Health doctoral program. With nearly two decades of clinical experience, he's supported patients across a wide range of chronic health challenges. To bring these insights to the many still struggling without answers, he wrote Silent Spark, an unseen force fueling chronic illness and how to heal, a book that sheds light on the often overlooked deepest roots keeping people sick.
Today, we're going to learn about the role of the microglia in both health and illness. Microglia are involved in neuroinflammation and neuroprotection; they're both a silent spark of inflammation and a regenerative force.
Dr. Stright's passion grew from helping his wife with Epstein-Barr and Lyme disease. He's been working in chronic illness for 20 years. Seeing some patients improve while others with similar stories and symptoms do not keeps him up at night. He prayed for understanding on how to help those not getting as far. He was introduced to the book The Angel and the Assassin about microglia research, initially for neurodegenerative conditions like Alzheimer's or dementia (reading for his mother-in-law with frontotemporal dementia). It clicked that chronic illnesses like Lyme, Epstein-Barr, mold illness activate these brain immune cells, creating a cascade of inflammation. Nobody in chronic illness is really talking about it; it's the elephant in the room. After researching journals and books, he had 100 pages of notes and realized he needed to write Silent Spark to make this dense topic easy to understand. It started with his wife, extended to his mother-in-law and patients, to help physicians and patients view chronic illness differently.
Microglia are the central nervous system's resident immune cell and align more with macrophages than anything else (specialized; macrophages built in bone marrow and proliferate peripherally, while microglia migrate in utero from the yolk sac, set up shop in the CNS, and stay there). They are in the spine, spinal cord, brain; densely in the limbic system and memory centers. When activated by toxicants, trauma, or chronic infection, they change morphology, become less docile (less nutrient delivery) and more phagocytic (envelop areas). Analogy: like a Japanese gardener (samurai/ninja with tools taken away, using rakes but silent assassins). The Angel and the Assassin frames them delivering nutrients normally but delivering a death blow to neural networks when activated.
M1 state is inflammatory/activated; M2 is anti-inflammatory/normal, delivering nutrients. M1 drives neuroinflammation; M2 is healing, cleanup, janitorial, resting, neuroprotective. Analogy: M2 like monkeys in Amazon tree selectively picking ripe fruit, pruning dead leaves, dropping to fertilize soil. M1 like monkeys going crazy on infection/toxicant, swinging wildly, breaking branches, creating chaos. Acute M1 activation saves the brain, but chronic long-term activation is detrimental. Goal: calm chronically active microglia.
In the biorestorative method (six nodes: autonomic nervous system, gut microbiome, terrain, neuroplastic retraining, epigenetic nutrition, heart-brain coherence), microglia fit into neuroplastic retraining. Chronic illness scientifically activates microglia chronically. Limit that activation. Classic states: cognitive decline, PANS, PANDAS, autism.
Microglia become sensitized/hyperaware from longstanding chronic infection, head trauma, Lyme, Epstein-Barr, mold. Like rubbing skin until rash. Tissues hold thoughts/traumas; ACEs (adverse childhood experiences) factor in. Lifestyle traumas make microglia hyperaware, secreting more inflammatory cytokines.
M1 (activated): secrete TNF-alpha, IL-6, IL-1beta, complement factors, ROS, iNOS, COX-2 (increases pain). M2 (repair/anti-inflammatory): IL-10, TGF-beta 1. TGF-beta 1 is anti-inflammatory in brain (from microglia) but problematic peripherally in mold illness (indicates chronic inflammation). Use natural ARBs like apigenin, fisetin, quercetin, honokiol oil (flavonoids act as ARBs peripherally). Aim for drug-like effects without side effects via biochemistry. M2 releases BDNF (brain-derived neurotrophic factor), GDNF (glial-derived neurotrophic factor), NGF (nerve growth factor) – ripe fruit fertilizing soil.
CytoDX (cytokines, TNF); TGF-beta 1; Shoemaker markers like MSH, VIP. Largely clinical; avoids labeling/diagnosis (branding leading to pharmaceuticals). Benefit without diagnosis is still benefit. Refuses labels like "Lyme" or "spoony". Ran CytoDX on patient: third of markers elevated; after 3 months diet/supplements, all gone except RANTES (autoimmunity).
Common thread: Lyme, Epstein-Barr often preceded by trauma (physical like head injury/bike crash, or emotional like family death) – straw that broke camel's back. Body often handles infections (majority have Lyme antibodies; 95% world has Epstein-Barr antibodies). Trigger sensitizes microglia. #1 trigger: head trauma or intense emotional trauma, but requires underlying stealth infection. Infection can be controlled/ in remission, but symptoms persist due to locked-in hyperaware microglia secreting cytokines (ILs, TNF-alpha) passing blood-brain barrier, communicating with peripheral immune-inflammation. Microglia like soldiers on high alert, cannot disengage even after war; original trigger gone, but microglia now core issue.
Even if triggers are largely mitigated, microglia can remain activated and hyperaware long after the initial insult. Microglia need to be acutely active to help the brain, but chronic activation must be limited. Research shows they stay hyperaware long after the trigger is gone. Viruses like Epstein-Barr remain latent in the body with antibodies present, similarly for Lyme. Microglia detect these via antibodies, continuing to secrete cytokines that drive inflammation. Treatment is comprehensive, addressing the whole body for Lyme or mystery illnesses, not just the primary issue.
Microglia act as the brain's bodyguards and maintenance crew with roles in immune surveillance, debris clearance, neuron support, synaptic pruning, damage repair, cell communication, and modulating brain activity. Upon encountering infection, toxin, or debris, ramified M2 (anti-inflammatory) microglia with long, spindly arms like a monkey climbing transform into ameboid (phagocytic). Arms swell, they grab and ingest threats via phagocytosis, breaking them down and releasing cytokines to recruit more cells.
Chronically activated ameboid phagocytic microglia accidentally degrade healthy synapses, leading to brain fog and cognitive decline. Further progression contributes to Alzheimer's and dementia. Activated microglia are found in dense populations in every Alzheimer's case, though Lyme doesn't inevitably lead to Alzheimer's.
Chronic microglial activation is like an unchecked engine causing cumulative wear. Use the bucket analogy: multiple triggers overflow the bucket, causing symptoms. Goal is to create margin by reducing cytokine signals and inflammation, not eliminating every trigger. Body doesn't isolate triggers by diagnosis (mold, Lyme, Epstein-Barr, sepsis, CRPS); all involve cytokine release. Calm the terrain to reduce microglial expression.
Microglia shift between M1 (pro-inflammatory) and M2 (anti-inflammatory) states regionally, not uniformly across the brain or spinal cord. Activation spreads via cytokines but isn't one cell dominating all.
Microglia prune synapses using a refrigerator analogy: In M2 state, they remove expired or unused connections like tossing bad food, organizing for memory consolidation and new neural pathways. They detect unused branches via chemicals and prune selectively. Underpruning leaves junk; overpruning empties the fridge, reducing BDNF and GDNF, weakening synapses, leading to debris, cytokine secretion, and cascades to Alzheimer's/dementia with memory loss.
Significant overlap between microglial activation and mast cell activation (MCAS), termed microglial activation syndrome by Brendan Vermier. Both secrete similar cytokines; mast cells peripheral, microglia central. Triggers overlap; treatments like quercetin and luteolin support both. Lowering microglial activation reduces MCAS susceptibility.
Microglia are highly active in the limbic system. Limbic retraining (Annie Hopper, Gupta, Carolyn Leaf) benefits from addressing microglial activation, as chronic neural networks are caustic, with stress/fear increasing inflammatory signals. Limbic system as threat assessor can trap in safety (bed under covers), but growth requires stretching with microexposures. Lowering stress reduces activation. Rewiring involves neurogenesis; microglia release BDNF/GDNF for new synapses. Activated microglia hinder retraining due to lacking growth factors. Strategies to calm microglia synergize with limbic programs, which rarely address nutrition/microglia.
No single vector-borne infection dominates, but mold toxins persist (use Dr. Neil Nathan's chelation strategies from Toxic). Mycoplasma forms lung biofilms, blocking toxin exhalation (70% detox via lungs; others: perspiration, defecation, urination, menstruation in women). Post-COVID, tidal edema surfaced debris, highlighting mycoplasma tied to Lyme/EBV.
COVID adds layer to microglial activation via persistent virus or spike protein. Unvaccinated fare better than vaccinated due to ongoing spike machinery. Tools: augmented NAC (research promising, not yet clinic-used), nutritional nicotine (non-addictive, anti-inflammatory, shifts to M2; Dr. Bryan Ardis), andrographis. Nicotine helped focus for writing.
Chronic microglial activation promotes persistent inflammation and excessive pruning, contributing to autism, PANS/PANDAS, MS, Parkinson's, ALS, Alzheimer's, schizophrenia, depression/anxiety. Protection turns to fire. Location matters: substantia nigra (Parkinson's), frontal cortex (anxiety/depression). High omega-6:omega-3 ratios prime microglia. Schizophrenia shows 70:1 ratio; anti-inflammatories may reverse some neurodegeneration.
40Hz light/frequency shifts M1 to M2, enabling plaque removal (90% in Alzheimer's mice via fiber optic; book Angels in the Assassin). Future: frequency-based corrections for FTD, Parkinson's (personal note: mother-in-law has FTD). Red light panels pulsing at 40Hz offer benefit.
Microglia contribute via lost discernment, attacking healthy CNS cells (e.g., anti-alpha synuclein on Neural Zoomer indicates Parkinson's risk). Cytokines drive systemic autoimmunity (lupus, Hashimoto's). Reducing activation clears CNS autoimmunity markers; ANAs drop (e.g., 1:360 to 1:80). Prioritize feeling better over marker elimination; antibodies persist post-resolution, avoid retesting to prevent limbic flares.
External factors like mold and mycotoxins contribute to microglial activation.
Exploring mold in the environment is something commonly recommended for patients, along with heavy metals, pesticides, chemicals, plastics, and other toxicants impacting microglia. Detoxification and drainage play a key role in mitigating chronically activated microglia. Terrain is king; cleaning the terrain allows the body to heal itself, as bodies are designed to do so. Terrain issues stem from toxicants in the environment, toxic thoughts needing capture and removal, and toxic people to remove oneself from. Build drainage networks like the French drain of all French drains for the marshy backyard terrain. This is pinnacle for any person, regardless of microglial activation; a clean terrain makes everything work better. Removing pesticides and mold is essential. Mold is a big problem but present daily; homeopathic constitutions like aspergillus, mucor, or penicillium are communication networks, and non-Candida yeasts are needed. Mycotoxins are problematic but not every problem. Mold toxin support groups or Lyme groups can turn into competitions of who has the moldier environment. If returning to a moldy home, healing is hard, similar to toxic family, perfume, or Airwick fresheners—environmental challenges needing removal or mitigation.
In Colorado hiking, many wear perfume detectable from 5 miles away, possibly deterring bears. In Colorado Springs mountains or mountain biking, smelling vanilla fields is common.
Microglia create reactive oxygen species (ROS), free radicals contributing to oxidative stress burden in chronic illness. Microglia act as gasoline in a spray bottle on a smoldering fire field, persisting the problem rather than causing it overall. Interventions to reduce ROS and support redox balance include hydrogen: inhale hydrogen for an hour a day at home or 30 minutes mixed with specialized lymphatic system. Hydrogen detoxifies by breaking down hydroxy free radicals. Other factors: methylene blue reduces ROS at mitochondria, supports M1 microglia morphing to ramified M2 phase, calming them, though it's a synthetic dye with ~1,200 studies. Future tech like 40 Hz vibratory sight lasers could resonate at substantia nigra or Alzheimer's areas like a laser knife for brain cancer, affecting microglia externally to internally, but not yet available. Methylene blue also helps some with Bartonella, a microglial trigger. Book discusses brilliant blue G dye.
Gut inflammation from foods, microbial dysbiosis, intestinal permeability impacts CNS microglia. Microglial activation affects motility, intestinal barrier function, microbial diversity. Gut microbiome is one of six nodes in biorestorative method. Gut lining cells eat short-chain fatty acids, primarily butyric acid or propionic acid; butyric acid nourishes gut lining. Leaky gut leads to inflamed gut, cytokine release, bacteria supporting glutamate over other neurotransmitters, causing anxiety and microglial activation via brain communication. Acetylcholine reduces microglial activation; glutamate is problematic. Calcium channel activation via voltage-gated ion channels: EMF/EMR opens them, depolarizes, secretes glutamate; glutamate breakdown byproduct is ammonia, accumulating in brain causing inflammation, more depolarization and glutamate. Cell phone to ear releases calcium channel ions locally, linking EMFs to microglial and gut changes.
For high glutamate (Vibrant testing), avoid glutamine powder for leaky gut as leftovers become glutamate, stirring pot in anxiety, depression, microglial activation, chronic illness. Avoid GABA much, as body should make it; raising GABA reflexively raises glutamate in teeter-totter homeostasis. If glutamate high and GABA low, giving 500 mg GABA could raise glutamate. Use gamma-aminobutyric acid (theanine), a glutamate scavenger lowering dietary and endogenous glutamate. Combine with butyric acid: body uses butyric acid to heal/seal gut lining, theanine reduces glutamate inflammation in brain/gut; leftovers form GABA properly. LPS (lipopolysaccharides) are microbial bits, extremely inflammatory; pour LPS on microglia in lab to activate instantly. High-dose LPS creates Alzheimer's in mice. LPS is toxic neuroinflammatory agent; future interventions may target melting LPS like microplastics.
Chronic microglial activation influences systemic inflammation, metabolic dysfunction, cardiovascular health via immune/hormonal imbalances. Gender differences: women and men have same glucocorticoid receptors on microglia, but women hold glucocorticoids longer, slower cortisol clearance. High cortisol/stress converts M2 to inflammatory M1 state. May explain 70%+ female patients. Estrogen is anti-inflammatory binding to microglia; drop in menopause may increase inflammation, cardiovascular issues (not purely microglial, many estrogen receptors body-wide). BHRT with topical estriol or bioidentical estriol supported. Progesterone reduces M1 to M2, always anti-inflammatory; big fan despite chiropractor limitations—top three to prescribe: progesterone, LDN, Naturthroid.
Book outlines SPARK diet for optimizing microglial function: Simple stabilizing foods, Polyphenols, Anti-inflammatory fats (olive oil, omega-3s, healthy nuts), Restorative minerals/micronutrients, Ketone-supporting strategies.
EMF/EMR mitigation: office uses SafeSpace, QuFi (emits scalar waves mitigating intrusive EMFs), Aries Tech pendants. Created additive with Quantum Vital Technologies (British Columbia) for all-natural skincare reducing EMF exposure. Distance key (field strength by proximity): finger rule for cell phone, avoid speakerphone. EMF-reducing stickers on devices. Reduction of exposure is cake, harmonizers icing. E-Shield cream similar.
Chronic microglial activation: mental/emotional triggers significant, including ACEs (adverse childhood experiences). EMDR desensitizes fear/phobia/addiction (prefrontal cortex, limbic system, amygdala), modulating to less stressed state, reducing microglial activation. Worked with Mark Wollen; profound. Vagus nerve tools: PTO, CES device, Apollo Neuro. Polyvagal theory (Porges): dorsal/ventral routes; social connection trumps all devices.
CRPS (complex regional pain syndrome), fibromyalgia tie to central sensitization and microglial activation. Central sensitization: chronic elbow pain spreads to shoulder/wrist in brain homunculus map; microglia increase it, get sensitized, act inappropriately. Reduce central sensitization and hypersensitive microglia; entire book on reducing activation/hyper-alertness. Address both microglial activation and symptomatic pain relief.
BBB breakdown allows triggers activating microglia. Tests: CRP, homocysteine, fibrinogen, TGF-beta 1, Cyrex panel for inflammation. Support barriers: plasmalogens, ProdromeGlia, egg lecithin vs. soy lecithin (animal-based synergistic). High-dose fish oil (2:1 EPA:DHA, 3-4g/day if gallbladder tolerates) builds BBB best.
Seizures activate microglia; chronic activation sensitizes to recurrent seizures—microglia keep coals burning. M2 state supportive; lower M1 to M2 for seizure disorders (chicken/egg).
eNOS (endothelial) benefits; iNOS (inducible) emergency flamethrower kills invaders but burns healthy tissue; microglia activate iNOS. Nitrate-nitrite-NO pathway avoids iNOS issues vs. arginine/citrulline.
Utilize the nitrate-nitrite-nitric oxide pathway in a specific manner. Avoid large doses of arginine or citrulline as they go down the iNOS pathway. Instead, use beets and green leafy vegetables, broken down by the gut microbiome to improve nitric oxide production. Avoid nitric oxide boosters for this reason. Epimorlin, kavain, or honokiol in moderation convert away from iNOS.
Peptides help with inflammation, modulating the immune system, and supporting the brain. Specific peptides that shift microglia back to the healthy supportive M2 state:
- BPC-157 and Cerebrolysin: Confirmed science reducing microglial activation.
- Thymosin alpha-1 and CMax: Theoretically strong indication, pushing toward M2 configuration.
- Sermorelin and Epimorlin: Believed to do the same via growth hormone increasing BDNF and GDNF, though lacking scientific literature proof.
Lazaroid (pill form) supports reducing zonulin intrusion into gut and blood-brain barriers, sealing them up.
Peptides are the wave of the future.
Tirzepatide in microdoses effective, but reticent due to issues with semaglutide and other GLP-1 drugs. Safety profile of other peptides is stout.
If trigger is infection or environmental toxicant, modulate immune response by balancing T-helper cells, creating tolerance. Tools like low-dose naltrexone (LDN), low-dose immunotherapy (Ty Vincent), desensitization (Dr. Debbie Ndubizu). This calms microglial activation.
LDN is an immune modulator. Andrographis (king of bitters) is an unsung hero: immune adaptogen, antiviral, antibacterial. Reduces hyperimmunity in Lyme or Epstein-Barr where cytokines are through the roof, benefiting the brain.
Sleep supports via magnesium, glycine, theanine, skullcap, honokiol, oleamide, valerian. Oleamide is a fatty substance building up in the nervous system when not asleep. At a certain point, brain breaks it down instead of anandamide, leaving CB1 and CB2 receptors open for calm effect via endocannabinoid system.
CBD or CBN helpful for microglia.
Melatonin fixes leaky mitochondria (release chemicals upregulating microglial activation). Use during the day (with light) to avoid messing with endogenous night supply; drains brain, increases glymphatic flow for toxin removal.
Melatonin plus dark equals sleep. Melatonin plus light not going to lead to sleep for most people.
Hypoxia (sleep apnea, mouth breathing, tongue fallback, lung biofilms) increases inflammasomes, thus microglial activation. CPAP powerful for calming microglia. Introduce oxygen controlledly. HBOT great but add antioxidants to avoid oxidative stress increasing inflammasomes. Hydrogen water before HBOT.
From book: PEA, LDN, EPA/DHA, resolvins/protectins, maritime pine, plant stem cells, turmeric/curcumin, resveratrol, kavain, honokiol, theanine, sulforaphane, vitamin D, vitamin B, magnesium (threonate/torate), apigenin, MCP (modified citrus pectin), kudzu, ashwagandha, andrographis, luteolin, choline, fisetin, ketones, NMN (NAD precursor), butyrate, nicotine.
Top tools: Luteolin, LDN, sulforaphane. Also PEA, honokiol, butyrate (takes all three daily). Honokiol oil, butyrate, nicotine, PEA top the list. Apigenin (less fisetin; hard to get past BBB but good peripherally). Fish oil. LDN highlighted but can't prescribe.
Many support mast cells too (twofers). Fucoidan beneficial for microglia (new to speaker).
Alpha-GPC mentioned in book. Phosphatidylcholine tricky: can be pro- or anti-inflammatory. Avoid for microglial activation; prefer plasmalogen-based like Prodrome Neuro or GA, high-dose fish oils, Egelesscopin. Huge fan of Prodrome GA.
Fisetin (senolytic): breaks down weakened cells. Apigenin (senomorphic): reduces inflammatory cytokines from dying cells. Senescent cells secrete inflammatory signals when dying/phagocytized (like keto flu).
Senescent microglia: long-lived sentinels. Some science says they renew from senescent state; others say new microglia break them down. Primed microglia: ready for action (like engine at 4500 RPM). Senescent: idling, spitting smoke.
No specific microglial combos yet (considering creating one). Uses honokiol oil, apigenin specifically, fish oil. Troscriptions sleep product (honokiol, agmatine, CBN, CBD) supportive for microglia.
No biologics/pharma better without chaos. Hydroxychloroquine good safety record. Minocycline (low-dose) for anti-inflammatory effects supports microglia. Excited about microglial transplant therapy (introduce fresh microglia, remove old).
Chronic Lyme: Minocycline calms inflammation, keeping under radar (personal story: wife on antibiotics for acne from age 13-23, no Lyme issues).
Ivermectin: reduces immune inflammatory cytokines, has a place.
Red light therapy, Violiite (red diode up nose, 40 Hz sync). 40 Hz sound therapy (binaural beats, not random YouTube). Satori table vibrates at music frequency for theta/gamma waves (microglia gamma).
VIP nasal spray (Dr. Shoemaker): not used yet, appropriate for patients. 40 Hz causes neurons to release VIP, signaling cleaning system.
Hydrogen therapy daily for oxidative stress. Periodic methylene blue. Nicotine every other day (7-12 mg). Mediterranean-style diet, gluten-free, limited dairy (raw organic A2 cow ok). Focus on electrical terrain: grounding (feet on ground/mat). Daily movement, detox/brain support.
Silent Spark: An Unseen Force Fueling Chronic Illness and How to Heal. Visit instituteforrestorativehealth.com.
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