• [[health-and-wellness]] [[long covid]] [[leo-galland]] Establishing a healthy gut brain axis after covid-19
  • TLDW Summary (Level 1):
    • Roadmap to re-establishing a healthy gut-brain axis
      • Step 1: Stop viral proliferation in the gut
      • Step 2: Reduce epithelial cell inflammation (in the gut)
      • Step 3: Reverse gut bacterial dysbiosis created by Covid-19
      • Step 4: Restore transport and metabolism of typtophan
      • Reduce Intestinal permeability
        • Step 5: Restore mucus layer (in the GI Tract)
        • Step 6: Restore tight junction integrity
      • Step 7: Detoxify intestines
      • Step 8: Create a gut microbiome that supports T-Cell memory
  • TLDW Summary (Level 2 Drilldown):
    • Prevent Viral proliferation in the gut
      • Curcumin, Quercetin, Baicalein, Glycyrrhizin, Artemsia annua L extract, Pro-biotic Bacillus Subtilis B-7092
      • Amoxicillin/Clavulanate, Oregano Oil
      • Polyphenols, especially bio-flavanoids rich foods and herbs
    • Reduce epithelial cell inflammation (in the gut)
      • Quercetin 600 mg bid, Mastic Gum (Pistacia Lentiscus Resin) 100mg bid, Curcumin 500mg bid, Omega-3 Fatty Acids 400 mg / day, Bovine Serum Immunoglobulins
    • Reverse gut bacterial dysbiosis created by Covid-19
      • Epigallocatechin Gallate (EGCG), Combination of Rice Bran and Quercetin, Baicalin, Curcumin
      • Butyrate a key post-biotic
      • A High fiber, polyphenol rich diet increases growth of F. Prausnitzii
      • Adherence to a Mediterranean diet elevates fecal levels of F. Prausnitzii
      • Pre-biotic oligosaccharides (FOS, GOS) increase F. Prausnitzii
      • Resveratrol inhibits enterococcus faecalis
      • Bifidobacterium Longum BB536
      • Bacillus coagulans GBI-30
      • A plant-based diet reduces levels of Ruminococcus Gnavus
      • Malvidin an Anthocyanin found in Berries reduces growth of R. Gnavus
      • Tryptophan supplementation
    • Restore transport and metabolism of typtophan
      • Vitamin D
      • Curcumin (500-1000 mg / day )
      • Resveratrol (200-1200 mg / day)
      • Anti-oxidants (work indirectly by controlling oxidative stress)
        • Alpha Lipoic Acid (300 mg bid)
        • NAC (600 mg tid)
      • Omega-3 fats (Indirect effect through Epelin signalling)
      • Cannabidiol (Indirect effect through Epelin signalling)
      • Quercetin
      • Humic Acid
      • Indole-3-Propionic acid (IPA)
      • Puerarin an isoflavonoid from kudzu root and Bifidobacterium Dentium
    • Restore tight junction integrity
      • Avoid Enterotoxic drugs like NSAIDs
      • Restore a healthy gut microbiome
      • Baicalin - Bioflavonoid from scutelleria baicelensis has curative and immunoregulatory properties with direct practical and clinical relevance
      • Luteolin, A Bioflavonoid with neuro-protective effects, enhances tight junction
      • Butyrate, Quercetin, Glutamine and Zinc separately and together enhance integrity of the epithelial barrier
      • Indole-3-Propionic Acid increases synthesis of tight junction proteins
    • Detoxify intestines
      • Zeolite
      • Humic Acid
    • Create a gut microbiome that supports T-Cell memory
      • Dietary support: High Fiber, Adequate Fat, Low Sugar, Fermented foods daily (Yogurt, Sauerkraut, Kimchi). Lactobacillus Plantarum
  • Level 3 Drilldown (Slides):
    • Roadmap to re-establishing a healthy gut-brain axis
      • Step 1: Stop viral proliferation in the gut
        • Persisting Viral Infection Contributes to Post Acute Sequalae to Covid (PASC)
          • Stool may contain SARS-COV2 for months after respiratory samples clear
          • Persisting Viral RNA and/or Viral proteins are found in multiple tissues at autopsy or surgery months after disease onset
            • Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae
          • Some patients experience marked improved of PASC after vaccination, anti-viral drugs and/or mono-clonal antibody therapy
          • Patients with Neuro-PASC have impaired function of T-Effector memory lymphocytes, an immune deficit seen with persistent antigenic simulation
            • Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination
        • Prevent Viral proliferation in the gut
          • Natural and/or synthetic anti-virals
            • Flavanoid-rich herbal products (protease inhibition, bacteriophage destruction), especially those with
              • Curcumin
              • Quercetin
              • Baicalein
              • Glycyrrhizin
            • Artemsia annua L
              • Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants
            • Pro-biotic Bacillus Subtilis B-7092
              • Secretes Human Interferon Alpha (IFN-α)
          • Natural and/or synthetic anti-bacterials
            • Amoxicillin/Clavulanate
              • Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2—New Data for a Possible Role in the Long COVID Pattern
            • Oregano Oil (Also inhibits prophage activation)
        • Dietary factors impact bacteriophage activity
          • Polyphenols, especially bio-flavanoids, disable or kill bacteriophages, including structural damage to the caspid(A capsid is the protein shell of a virus, enclosing its genetic material), inhibiting bacteriophage activity and infectivity
          • Oregano oil suppresses multiple types of prophages preventing their incorporation into the bacterial genome
          • Note: The natural sweetener stevia, promotes the activity of multiple species of bacteriophages, increasing their impact on bacterial hosts (So use stevia with caution)
            • Dietary Modulation of Bacteriophages as an Additional Player in Inflammation and Cancer
        • Bacillus Subtilis B-7092 and anti-viral pro-biotic
          • Isolated from the siberian tundra in the 1960s
          • Developed by soviet scientists as an immune-boosting pro-biotic with insertion of a plasmid that releases alpha-interferon(anti-viral, to which SARS-COV2 is sensitive)
          • Further developed in Ukraine as Subalin and in Russis as Betom 1.1 and Tundrex in USA
          • Personal experience:
            • Most useful for restoring a healthy micro-biome after treatment of GI Infection
            • May also, on its own, combat viral or bacterial infection (Campylobacter)
            • Controls GI Symptoms of patients with acute and long covid-19
      • Step 2: Reduce epithelial cell inflammation (in the gut)
        • Reduce epithelial cell inflammation (break the inflammation-dysbiosis cycle)
          • Inflammation increases nitric oxide synthesis, raising nitrate concentration of inflamed tissue
          • A high nitrate environment changes bacterial growth patterns
          • Anti-inflammatory bacteria are stunted
          • Pro-inflammatory bacteria are stimulated
          • Their growth created more inflammation and maintains a high nitrate concentration
        • Controlling intestinal inflammation lays the foundation for reversing gut bacterial dysbiosis
          • Quercetin 600 mg bid
            • Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition
          • Mastic Gum (Pistacia Lentiscus Resin) 100mg bid
            • Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis
          • Curcumin 500mg bid
            • Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection
          • Omega-3 Fatty Acids 400 mg / day
            • Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System
          • Magnolia bark extract (Magnolol, Honokiol)
            • Magnolol and Honokiol Attenuate Apoptosis of Enterotoxigenic Escherichia Coli-Induced Intestinal Epithelium by Maintaining Secretion and Absorption Homeostasis and Protecting Mucosal Integrity
          • Bovine Serum Immunoglobulins
            • Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART
        • Key role of Quercetin in reversing intestinal inflammation
          • Supplementation of dietary Quercetin and Vitamin E promotes the intestinal structure and immune barrier integrity
          • Furthermore, Quercetin enhances barrier integrity in CACO-2 cells by inducing re-modelling of epithelial tight junctions, as well as protects gastric mucosa against ulcerogenic agents
          • Quercetin also attenuates the effects of C. Rodentum induced colitis, inhibit the production of pro-inflammatory cytokines, as well as upregulates the expression of anti-inflammatory cytokines in the colon
        • Gut microbiome at disease onset predicts the development of PASC
          • Covid-specific effects
            • Gut microbiome of patients who developed PASC was characterized by lower levels of Faecalibacterium Prausnitzii and higher levels of Ruminococcus Gnavus and Bacteriodes Vulgatus
            • Butyrate producing bacteria, especially Faecalibacterium Prausnitzii and Bifidobacterium Pseudocatenulatum showed the largest inverse co-relations with PASC at 6 months
            • Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome
      • Step 3: Reverse gut bacterial dysbiosis created by Covid-19
        • Restore depleted bacteria, restrain inflammatory bacteria
          • General effects of specific flavanoids, curating the gut microbiome
            • EGCG Treatment (Epigallocatechin Gallate (EGCG) Promotes the Immune Function of Ileum in High Fat Diet Fed Mice by Regulating Gut Microbiome Profiling and Immunoglobulin Production) resulted in stimulation of the beneficial bacteria, Especially Bifidobacteria and inhibits potential pathogenic bacteria. Fusibacterium Varum, Bilophila and Enterobacteriaceae
            • The combination of Rice Bran and Quercetin served to enrich beneficial bacteria and reduce potential opportunistic pathogens
            • Baicalin
              • Amerliorates senscence status and improves cognitive function in mice and that this effect might be attributable to suppression of cortical proinflammation cytokines and modulation of the intestinal microbiome
              • Improved insulin resistance nad system inflammation in diabetic rats
              • Modulated gut microbiota composition and enhanced gut barrier function
              • SCFA producing bacteria were upregulated and pathogens were down regulated
            • Curcumin and its metabolites can have health benefits by eliminating intestinal microflora dysbiosis
        • Importance of Butyrate a key post-biotic
          • Gut Dysbiosis has a significant impact on central and system homeostasis, via decreased butyrate and melatonin driving sub-optimal mitochondria functioning
          • Butyrate produced by microbial fermentation in the bowel has a protective effect towards maintaining the integrity of the gut epithelial barrier, which can decrease inflammatory responses in inflammatory bowel disease (IBD) such as Crohn's disease, although the underlying mechanism remains unknown
          • Cell and animal models of colitis demonstrate that butyrate mediated activation of the GPR109A receptor, which is known to suppress inflammatory effects in various diseases, underlies its protective effects on the colon health, results demonstrate that activating GPR109A may represent a novel approach to treat IBD
          • Butyrate readily crosses into the circulation it is likely that the immune and glia dampening effects of butyrate also involve the induction of melatonin in these reactive cells. Butyrate both directly and via melatonin will have significant impacts on the gut, immune and other cells via mitochondria regulation.
          • Mitochondria and the Gut as crucial hubs for the interactions of melatonin with sirtuins, inflammation, butyrate, tryptophan metabolites, and alpha 7 nicotinic receptor across a host of medical conditions.
        • CNS and Systemic Effects of Butyrate
          • Histone deacetylase inhibitor: Activates quiescent genes, including gene for brain-derived neurotropic factor (BDNF), enhancing neuronal recovery
            • The Gut-Brain Axis, BDNF, NMDA and CNS Disorders
          • Activates G-Protein coupled receptors (GPR41, GPR43, GPR109A), which regulate immune responses and inflammation
            • Regulation of inflammation by short chain fatty acids
        • Toward reversing gut bacterial dysbiosis among people with PASC
          • A High fiber, polyphenol rich diet increases growth of F. Prausnitzii
          • Adherence to a Mediterranean diet elevates fecal levels of F. Prausnitzii
            • Adherence to a Mediterranean Diet Influences the Fecal Metabolic Profile of Microbial-Derived Phenolics in a Spanish Cohort of Middle-Age and Older People
          • Pre-biotic oligosaccharides (FOS, GOS) increase F. Prausnitzii
            • The Gut-Brain Axis, BDNF, NMDA and CNS Disorders
          • Resveratrol inhibits enterococcus faecalis, an inflammatory microbe associated with worse outcome for acute covid and alters gut/lung microbiome to limit super antigen induces respiratory inflammation.
            • Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin
            • The Bidirectional Interactions between Resveratrol and Gut Microbiota: An Insight into Oxidative Stress and Inflammatory Bowel Disease Therapy
            • Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut
        • Pro-biotics that enhance the growth of Faecalibacterium Prausnitzii
          • Randomized controlled clinical trials in humans
            • Bifidobacterium Longum BB536 in children and adults with allergy
            • Bacillus Coagulans GBI-30 in elderly adults
            • Influence of Bifidobacterium longum BB536 intake on faecal microbiota in individuals with Japanese cedar pollinosis during the pollen season
            • Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children
            • Bacillus coagulans GBI-30, 6086 Modulates Faecalibacterium prausnitzii in Older Men and Women
            • Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086
        • Ruminococcus Gnavus and the Gut-Brain Axis
          • Ruminococcus Gnavus consumes and thins the intestinal mucous layer
          • Ruminococcus Gnavus converts tryptophan into tryptamine which can trigger migraine and interfere with circulation and may limit availability of Tryptophan for other reaction
          • Ruminococcus Gnavus produce Isoamylanine, A neuro-toxic metabolite that causes cognitive dysfunction by destroying glial cells.
            • Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death
          • A plant-based diet reduces levels of Ruminococcus Gnavus
            • Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults: The NU-AGE Study
          • Malvidin an Anthocyanin found in Berries reduces growth of R. Gnavus in animals
            • Malvidin 3-Glucoside Modulated Gut Microbial Dysbiosis and Global Metabolome Disrupted in a Murine Colitis Model Induced by Dextran Sulfate Sodium
        • Amino acids, Neuro-transmitters and the gut microbiome
          • Many neuro-transmitters are derives from dietary pre-cursors (both compete for transport into cells with other large neutral amino acids - LNAA)
            • Tryptophan->Serotonin->Melatonin
            • Phenylalanine->Tyrosine->Dopa->Dopamine->Norepinephrine
          • Bacteria both produce and respond to neuro transmitters, which impact their virulence and proliferation
          • ACE2, the receptor for SAES-COV-2 is an essential chaperone for absorption of LNAA from the small intestine. Loss of ACE2 especially impairs tryptophan absorption
          • COVID-19 created ACE2 deficit, which may produce tryptophan malabsorption
      • Step 4: Restore transport and metabolism of typtophan
        • Enhance ACE2 Activity to increase Tryptophan transport
        • Decease Serotonin oxidation with Flavonoids
        • Cannabidiol (CBD) has serotoninergic and ACE2 enhancing effects
        • Wang et al. found that Curcumin, Among 14 other tested food chemicals stimulates the most serotonin (5-HT) from cultures EC cells. Notably they also respond to and have an effect on bacterial metabolites and population, similar to to the neurometabolite signalling pathway.
        • Recent research has established a bi-directional relationship between cell serotonin production and gut microbiota. Although secretion of 5-HT can increase gut colonization of specific microbiota, reversibly changes to the microbiota can encourage greater cell and peripheral serotonin concentrations
        • Enhancement of ACE2 Activity by natural products
          • Vitamin D
          • Curcumin (500-1000 mg / day )
          • Resveratrol (200-1200 mg / day)
          • Anti-oxidants (work indirectly by controlling oxidative stress)
            • Alpha Lipoic Acid (300 mg bid)
            • NAC (600 mg tid)
          • Omega-3 fats (Indirect effect through Epelin signalling)
          • Cannabidiol (Indirect effect through Epelin signalling)
        • Quercetin inhibits serotonin oxidation, but may reduce Serotonin synthesis
          • Quercetin improves behavioral deficiencies, restores astrocytes and microglia, and reduces serotonin metabolism in 3-nitropropionic acid-induced rat model of Huntington's Disease
          • Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon
          • Typically pull Quercetin out of the treatment after 2-3 weeks to see how patient responds (as Quercetin may reduce Serotonin Synthesis)
        • Beneficial Tryptophan Metabolite Indole-3-Propionic acid is produced by gut bacteria
          • IPA production by Clostridium Sporogenes is required for efficient regeneration of peripheral nerves and inhibits neutrophil chemotaxis. Its production is stimulated by intermittent fasting in Mice
            • The gut metabolite indole-3 propionate promotes nerve regeneration and repair
          • IPA Works with IFN-Alpha to decrease CNS Inflammation
            • Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
          • IPA decreases the synthesis of bacterial endotoxins and increases the integrity of human tight intercellular junctions in rats
            • Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats
          • IPA increases tight junction proteins and gut mucus secretion of human colonic mucosal cells
            • Indole-3-propionic Acid Improved the Intestinal Barrier by Enhancing Epithelial Barrier and Mucus Barrier
      • Reduce Intestinal permeability
        • Step 5: Restore mucus layer (in the GI Tract)
          • Indole-3-Propioninc acid increases mucus secretion
          • Puerarin an isoflavonoid from kudzu root and Bifidobacterium Dentium each restore and fortify the intestinal mucus layer
            • Puerarin Rebuilding the Mucus Layer and Regulating Mucin-Utilizing Bacteria to Relieve Ulcerative Colitis
            • Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways
          • Quercetin is effective in recovering gut microbiota in mice after anti-biotic treatment and may act as pre-biotic in combating gut dysbiosis
          • Humic Acid Stays in the intestines and chelates Glyphosate and other toxins, restored mucus later and calms gut epithelial cells
            • Supplementation of Dietary Quercetin and Vitamin E promotes the intestinal structure and immune barrier integrity in aged breeder hens
            • Quercetin improves gut dysbiosis in antibiotic-treated mice
        • Step 6: Restore tight junction integrity
          • Avoid Enterotoxic drugs like NSAIDs
          • Restore a healthy gut microbiome
          • Baicalin - Bioflavonoid from scutelleria baicelensis has curative and immunoregulatory properties with direct practical and clinical relevance
          • Luteolin, A Bioflavonoid with neuro-protective effects, enhances tight junction
          • Butyrate, Quercetin, Glutamine and Zinc separately and together enhance integrity of the epithelial barrier
          • Indole-3-Propionic Acid increases synthesis of tight junction proteins
          • The effect of phospholipids and fatty acids on tight-junction permeability and bacterial translocation
          • Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients
      • Step 7: Detoxify intestines
        • Aspergillus Flavus which produces aflatoxins, overgrows in the gut of people hospitalized with Covid-19
          • Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge
        • Beta-Glucan from fugal cell walls is found in plasma of people with long covid
          • Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling
        • Zeolite can trap and remove a wide range of toxins in the human body, absorbs aflatoxins
        • Charcoal and Humic Acids influence selected gastrointestinal microbiota, enzymes, electrolytes, and substrates in the blood of dairy cows challenged with Glyphosate in GMO feeds
      • Step 8: Create a gut microbiome that supports T-Cell memory
        • Enhance function of T-Effector memory cells, depleted in people with neuro-PASC
          • Important for prolonged post-infectious immune memory
          • (T-Effector memory cells are) Depleted in people with Neuro-PASC
            • Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein
          • Thrive on fatty acid oxidation, butyrate and presense of lactobacilli
          • Dietary support: High Fiber, Adequate Fat, Low Sugar, Fermented foods daily (Yogurt, Sauerkraut, Kimchi). Lactobacillus Plantarum
          • Enhancement of Mitochondrial Function with Nutirents
            • Mitochondrial respiratory capacity is a critical regulator of CD8+ T Cell Memory Development
        • Lactobacillus Plantarum
          • Grows on plants
          • Found in fermented vegetables (Sauerkarut, kimchi) and supplements
          • Immune enhancement is its best effect
          • Lactobacillus plantarum reduced infection after major abdominal surgery by 70%
            • Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery - results of a prospective trial
          • Lactobacillus Plantarum improved gut barrier function, decreased growth of gut pathogens and improved clinical outcomes of patients with pancreatitis
            • Effect of Lactobacillus plantarum enteral feeding on the gut permeability and septic complications in the patients with acute pancreatitis