Chronic Gut-Lung Axis Dysfunction

Integria Healthcare Symposium 2021Restoring the Seat of Health 1

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Chronic Gut-Lung Axis Dysfunction

Craig WainwrightAdvDip of Health Sciences (Nat)Bach of Phar

Integria Healthcare Symposium 2021Restoring the Seat of Health 2

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Patient Overview• 56 year old woman, 5 adult children

• Gastrointestinal symptoms

• IBS - flatus since childhood, as an adult - chronic abdominal upset,distension, stabbing pains associated with multiple foods

• Now experiencing loose stools 1-2/day, type 5 and 6 (Bristol stool chart),colour varies between light, clay and yellow brown. Stool looser forsaturated fatty foods and fibre rich foods

• Long history of constipation, with stools every 2-3 days, up to a weekbetween stools

Patient Overview

• Neurological symptoms

• Migraines

• First presented at 10 years of age, prior to menarche

• Worsened by oestrogen containing OCPs, all 5 pregnancies andIVF cycle

• Now post menopausal but still recurrent

• Changed in nature, previously auras, vertigo and nausea. Now withoutaura. Significant episodes of dizziness and travel sickness

Integria Healthcare Symposium 2021Restoring the Seat of Health 3

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Patient Overview

• Respiratory system

• Recurrent lung infections, small airways disease (bronchiolitis) (main reason for seekingtreatment)

• Asthma from age 2. Bronchitis episodes since childhood. Serious recurrence in 2010

• Pneumonia whilst on holiday in Croatia (2017). Initially six months to clear.Increasing frequency since, 16 subsequent episodes (10 in most recent 12 months),all requiring antibiotic therapy

• Acute symptoms of fever, chest pain, productive cough, occasional wheeze.Residual continual phlegm between episodes

• Mild to moderate mucosal disease of right and left maxillary sinus, with occludedostiomeatal unit (OMU), tonsils and adenoids removed at 7 years of age

• General fatigue despite feeling better for daily exercise (cardio, weights, walking)

• Family history - Father: asthma, bronchitis; Mother: hay fever

Current Medication

• Breo-Ellipta inhaler (fluticasone furoate and vilanterol) daily• Salbutamol inhaler daily and as needed• Telfast 180 mg daily• Roxithromycin 300 mg on hand for lower respiratory tract infection

• Supplements• Pancreatic enzymes with Fennel and Gentian• Magnesium chelate plus B vitamins powder• OTC Women’s 50+ multivitamin• OTC gut relief powder (glutamine, Acacia Gum, quercetin, Globe Artichoke, Marshmallow, zinc)• OTC menopause relief (Dong Quai, Kudzu, Chaste Tree)• OTC Multi strain probiotic• OTC Kelp

Integria Healthcare Symposium 2021Restoring the Seat of Health 4

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Diet

• Previously advised to follow low FODMAPs and low salicylate diet

• Overnight fasting (14-16 hours)

• As a result, limited diet, eating the same foods each day, few vegetables or fruits,nil pulses from previous advice and associated gut symptoms

• Late breakfast - egg white and oat flour/fibre pancake

• Afternoon snack - rice cakes with cream cheese, apple (no skin)

• Dinner - seafood, green beans, cooked oats with natural yoghurt

• Occasional milk chocolate (caused bloating, GIT pain and loose stools)

• Good water intake, nil coffee

• Regular added salt

Key Pathology Findings

• Microbiome

• Previous microbiome analysis, showed low resistant starch

• WBC count

• Raised neutrophil to lymphocyte ratio (4-9:1), many years of consistently lowlymphocytes (<1x109/L), raised monocytes (>0.5x109/L), CD3, CD8+/CD3+, IgE (>100)

• Low NK cells

• Tissue damage

• Raised lactate dehydrogenase (LDH) (variable but often 280+ U/L)

• Thyroid

• TSH normal, T4 9.9 (9.1-19.6 pmol/L), T3 3 (2.4-5.9 pmol/L), nil thyroid antibodies (TPO,TG)

Integria Healthcare Symposium 2021Restoring the Seat of Health 5

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Key Pathology Findings Continued

• Nutrients

• Adequate vitamin A, B1, B2, C and D, iron, zinc, copper, selenium

• Marked elevation of urinary iodine (349 µg/L)

• Respiratory

• Multiple lung sputum tests varied between Haemophilus influenzae orno finding

• Respiratory testing of forced expiratory flow (FEF) at 40-80%, respondedto inhaled bronchodilators. Assessment taken in between acute infections

Enaud R, Prevel R et al. The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalks. Front Cell Infect Microbiol.

2020;10:9.

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Integria Healthcare Symposium 2021Restoring the Seat of Health 6

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Initial Consultation

• Advised further testing of antinuclear antibodies (ANA), immunoglobulin panel,histamine, tryptase, and rT3

• Underlying/ exacerbating factors

• Bowel dysbiosis/ lack of microbiome diversity, SIBO (secondary to high antibioticintake), gut-lung axis modulation1

• Allergic lung sensitisation secondary to chronic lung infection, and suppressed lungimmunity, increased pneumonia risk secondary to inhaled corticosteroid, possiblefungal lung overgrowth and increased airborne reactivity1-5

• Potential mast cell activation

• Subclinical underactive thyroid (subsequent basal temp readings of 35.5 - 36o)

References for Previous Slide

1. Singanayagam A, Glanville N et al. Corticosteroid suppression of antiviral immunityincreases bacterial loads and mucus production in COPD exacerbations. Nat Commun.2018;9(1):2229. doi: 10.1038/s41467-018-04574-1.

2. Singanayagam A, Glanville N et al. Inhaled corticosteroid suppression of cathelicidindrives dysbiosis and bacterial infection in chronic obstructive pulmonary disease.Sci Transl Med. 2019;11(507):eaav3879. doi: 10.1126/scitranslmed.aav3879.

3. Rapeport WG, Ito K et al. The role of antifungals in the management of patients withsevere asthma. Clin Transl Allergy. 2020;10(1):46. doi: 10.1186/s13601-020-00353-8.

4. Yii AC, Koh MS et al. The emergence of Aspergillus species in chronic respiratorydisease. Front Biosci (Schol Ed). 2017;9:127-138. doi: 10.2741/s477.

5. Landt E, ﾇolak Y et al. Chronic cough in individuals with COPD: A population-basedcohort study. Chest. 2020;157(6):1446-1454. doi: 10.1016/j.chest.2019.12.038.

Integria Healthcare Symposium 2021Restoring the Seat of Health 7

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Initial Prescription

• Focus to decrease GIT sensitisation

• Dietary modification: avoid cream cheese, halve salt intake

• Modified activated clinoptilolite (MANC) 400 mg - 1 TDS before meals (histaminechelation)

• Levagen+™ PEA 600 mg BD to decrease GIT sensitisation, intestinalpermeability and inflammation, possible mast cell activation and histaminergicsensitisation1,2

• Probiotic containing Lactobacillus rhamnosus LGG (20 billion), L. paracasei (L-33) for allergy reduction, immune modulation

• Maintain previous supplements: gut relief formula, menopause relief, digestiveenzymes, multivitamin, and magnesium

• Cease Kelp (excess iodine)

References for Previous Slide

1. Couch DG, Cook H et al. Palmitoylethanolamide and CannabidiolPrevent Inflammation-induced Hyperpermeability of the human gut invitro and in vivo-A randomized, placebo-controlled, double-blindcontrolled trial. Inflamm Bowel Dis. 2019;25(6):1006-1018.doi: 10.1093/ibd/izz017.

2. Capasso R, Orlando P et al. Palmitoylethanolamide normalizes intestinalmotility in a model of post-inflammatory accelerated transit: involvementof CB₁ receptors and TRPV1 channels. Br J Pharmacol. 2014Sep;171(17):4026-37. doi: 10.1111/bph.12759.

Integria Healthcare Symposium 2021Restoring the Seat of Health 8

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Cani PD, Plovier H et al. Endocannabinoids—at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol. 2016;12(3):133-43.

Second Visit (3 weeks later)

• GIT more settled. Regular singular daily stool, firmer, less yellow. Much lessflatus

• Able to reintroduce brussel sprouts, peas, pumpkin, sweet potato, carrot, swede

• Headaches and hot flushes diminished (able to reduce menopause formula)

• Energy improved despite less sleep (lifestyle)

• No lung exacerbation, nor asthma episodes, sinuses/catarrh unchanged

• Treatment adjustments

• Broad spectrum antimicrobial (Oregano, Thyme, Myrrh, Berberine and Garlic),1 cap TDS (3 days on, 4 days off) increasing to 2 caps TDS

• NAC Powder 1 g TDS - biofilm eradication, modulate lunginflammation/immunity1

Arranz L, Fernández C et al. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med. 2008;45(9):1252-62. doi: 10.1016/j.freeradbiomed.2008.07.014

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Integria Healthcare Symposium 2021Restoring the Seat of Health 9

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Third Visit (2 weeks later)

• No bloating or stabbing pains, dailyfirm stool

• 2 episodes of nausea and headachewith cheese platter and preservedmeat

• Continued good tolerance ofvegetables added previously

• No acute lung exacerbations, minornocturnal asthma cough. No changein sinus congestion

• Treatment adjustments

• Saline nasal spray TDS, reducedigestive enzymes to BD

• Added lecithin 1200 mg each meal

• Thyroid support (inositol, selenium,Withania, activated Bs)

• Ceased previous multivitamin

• Reduce MANC to BD

Fourth Visit (4 weeks later)

• Stools: darker, firm daily stool

• No nausea, bloating, or pain - even with fatty food

• One night of fever and chills. No lung pain, no antibiotic needed

• Testing

• High histamine (0.7 nm/mL), rT3 214 (230.0 - 540.0 pmol/L),low normal serum calcium 2.20 (2.15-2.60 mmol/L)1

• Improved basal body temp (36 - 36.3o), ANA negative, low tryptase, IgA,IgG and IgM (low to normal)

1. Dai Q, Zhu X et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018;108(6):1249-1258. doi: 10.1093/ajcn/nqy274.

Integria Healthcare Symposium 2021Restoring the Seat of Health 10

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Fourth Visit (4 weeks later)

• Treatment adjustments

• Magnesium citrate 150 mg BD1

• Added herbal tonic• Tinospora 40 mL• Echinacea Premium 50

mL• Astragalus 50 mL• Panax Ginseng 30 mL• Baical Skullcap 45 mL

• Dose: 7.5mL BD.For thyroid and immuneenhancement, to reduce allergicsensitisation

Fourth Visit (4 weeks later)

• Increased broad spectrum antimicrobial to 2 TDS, 10 days on, 4 days off

• Reduced Levagen+™ PEA to 300 mg BD, ceased digestive enzymes

• Had provided additional instructions for any acute lower respiratory infection

• Acute Immune Support 1 tab every 3 hours

• Has continued to improve. Added green leafy vegetables with no adverse effects

• Pathology changes

• T4 (15 pmol/L), T3 (3 pmol/L) (still low)

• Normalisation of neutrophil/lymphocyte numbers and ratio, reduction ofmonocytes to normal (0.29x109/L)

• Histamine reduced to 0.6 nm/mL (from 0.7), LDH now below 250 U/L

Integria Healthcare Symposium 2021Restoring the Seat of Health 11

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Current Status

• To this day, only minor LRTI requiring a 5-day course of Roxithromycin(per GP instruction), though no fever, no lung pain, no lung expectorationor consolidation. Recovered well

• Another episode of thick upper tracheal phlegm, wheeze, some fatiguebut no fever, no lung pain. Implemented Acute Immune Support 1 tabevery 3 hours. Resolution within 3 days

• Complete resolution of sinus congestion, postnasal drip, and headaches

Current Status

• Subsequent removal of breast implants. Previous discussion about theeffect of adjuvant silicon on inflammation and immune regulation even ifimplants intact1 No complications or infection

• Provided liver support pre and post procedure, St Mary's Thistle Tablets1 tab TDS and liposomal glutathione 100 mg daily plus ConnectiveTissue & Microcirculation Formula 2 tabs BD

• No adverse GIT effect from routine antibiotic prescription post surgery

• Headaches/migraine returned post surgery but resolved quickly

• Added partially hydrolysed Guar Gum (PHGG) and Acacia Gum powder.Well toleratedPerricone C, Colafrancesco et al. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and

diagnostic aspects. J Autoimmun. 2013;47:1-16. doi: 10.1016/j.jaut.2013.10.004.

Integria Healthcare Symposium 2021Restoring the Seat of Health 12

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Current Status

• Further adjustments

• Added Chlorella powder, up to 3 g BD (no problems with bowel tolerance)- immune enhancement and reduction of allergic responses1,2

• Weekly alternation of broad-spectrum antimicrobial with conifer greenneedle complex (antioxidant, immune enhancement and anti-microbial)

References for Previous Slide

1. Bae MJ, Shin HS et al. Inhibitory effect of unicellular green algae(Chlorella vulgaris) water extract on allergic immune response. J SciFood Agric. 2013;93(12):3133-6. doi: 10.1002/jsfa.6114.

2. Kwak JH, Baek SH et al. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural killer cell activityand early inflammatory response (randomized, double-blinded, placebo-controlled trial). Nutr J. 2012;11:53. doi: 10.1186/1475-2891-11-53.

Integria Healthcare Symposium 2021Restoring the Seat of Health 13

Chronic Gut-Lung Axis DysfunctionCraig Wainwright

Thank you for listening