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



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



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



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)



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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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.



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)


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.



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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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


• 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.





• 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


• 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



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.



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)


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.



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chronic gut-lung axis dysfunction

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