The last few decades of research have seen an acceleration of understanding into the numerous microbial communities that reside on and within us. These can be found all over the skin, in the mouth, the airways, the vagina, with the largest and most significant residing in the gastrointestinal tract. This gut microbiome assimilates many dietary nutrients indigestible by the human body, whose presence and metabolites not only modulate GI immunity but also impact the immune responses of distal organs, such as the liver, brain and lung.

Evidence of a gut-lung axis

The development of a healthy immune system is dependant on the presence of a healthy gut microbiome.  Less well known is that a healthy lung microbiota is essential in the maturation and homeostasis of lung immunity, reducing Th2-associated cytokine production after an allergen challenge and inducing regulatory cell production early in life, as well as establishing resident memory B cells, which are important weapons against viruses such as influenza.

But there is also a long reaching impact on the pulmonary immune system from the gut microbiota.  Gut bacteria along with their metabolites, such as short chain fatty acids (SCFAs), and bacterial fragments, can translocate across the intestinal barrier and enter systemic circulation through the mesenteric lymphatic system to modulate the the lung immune response.  SCFAs act as signalling molecules in the lungs on resident antigen presenting cells to help attenuate inflammatory and immune responses.

There is clear evidence of a common mucosal immune system operating between the gut and lung.  T and B cells produced in the Peyer’s patches found in the gut, migrate to intestinal and non-intestinal sites, including the bronchial epithelium, where they transfer important immunological information through antibodies, particularly IgA.  Innate lymphoid cells involved in tissue repair are also recruited to the lungs from the gut using inflammatory signals from IL-25.  Commensal gut segmented filamentous bacteria (SFB) have been shown to regulate the CD4+ T-cell polarisation into the Th17 pathway, and its over expression can exacerbate pulmonary fungal infections and autoimmune lung conditions.

Dysbiosis usually manifests as the replacement of a complex and diverse community of anaerobes with a less diverse community and increased facultative anaerobes, and is  driven by a poor diet, the use of broad-spectrum antibiotics, stress, alcohol or drug abuse, age and genetics, amongst others.  This affects the lungs, changes in diet during infancy alter the lung microbiome as do faecal transplants in rats.

Microbiome imbalances are clearly implicated in asthma, CPOD and cystic fibrosis.  For example, a reduction in Bifidobacteria and increase in Clostridia in the gut microbiome is associated with asthma in early life.  Dysbiosis increases toll-like receptor (TLR) activation and the release of gut NF-κB, which is associated with an increased lung inflammatory response during influenza in mice.  TLR activation is implicated in the cytokine storms recently seen in the most serious COVID-19 cases.

Lung pathologies can also affect the gut.  Influenza virus infection in the murine respiratory tract increases Enterobacteriaceae and reduces Lactobacilli and Lactococci in the gut microbiota.  Salmonella nasal inoculation promotes salmonella specific gut immunisation, which depends on lung dendritic cells.  Inhalation of lipopolysaccharides by mice disturbs their gut microbiome.

This research suggest a close correlation between the two microbiota and the presence of a host-wide network influencing each others’ immune homeostasis.  This has clear implications in the clinic.  Gut microbiome balance must be taken into account when targeting the lungs and needs support after any lung based infection.

Improving microbiome composition

Good dietary habits significantly impact our microbiome composition and especially its production of beneficial metabolites.  A diet rich in plant diversity, polyphenols and fibre results in a more diverse bacterial community with a richer output of SCFA’s, which have been shown to significantly benefit human health and favourably modulate host immune responses.  It’s best to introduce diversity gradually, eventually aiming for 30 different plants over a week.

Another approach can be to encourage the growth of ‘keystone’ species such as Akkermansia municiphilia and  Faecalibacterium prausnitzii within the microbiome, which have been shown to modulate the rest of the microbiome, helping to maintain a healthier microbial balance, and also improve tight junctions in the gut epithelium.  This can be achieved using targeted pre-biotics of researched non-digestible oligosaccharides through diet or supplementation, such as kiwifruits and mushrooms.

More and more research is also highlighting the beneficial role of polyphenols in the functioning of a healthy microbiome and in the maintenance of its barrier functions, highlighting the importance of including the rainbow in the diet.  Microbes metabolise polyphenols to release antimicrobial, antioxidant, anti-inflammatory and anti-proliferative metabolites, which act at both a gut and systemic level to counteract pro-oxidant and/or pro-inflammatory responses.

Probiotics can block pathogenic bacterial effects by competing with them for adherence to the intestinal epithelium and by producing their own bactericidal substances.  They also regulate immune responses by enhancing innate immunity and modulating inflammation through TLR activation and can promote intestinal epithelial homeostasis by improving cell survival, enhancing barrier function and stimulating protective responses.  One double-blind, placebo-controlled study using the probiotic MegaSporeBiotic, showed that 30 days of supplementation could reduce endotoxemia after a high fat meal by 45%, as well as significantly reduce inflammatory cytokines.  (McFarlin et al., 2017)

MegaSporeBiotic is a probiotic blend of 5 Bacillus spores, and this research suggests that the spores were able to strengthen the integrity of the intestinal lining to keep endotoxins out of the bloodstream.  One of the spores, Bacillus clausii, has also been shown to prevent recurrent respiratory infections in children and decrease nasal cytokine production in allergic reactions. Many probiotics struggle to survive the harsh gastric passage, but spores can and do, entering the intestines completely viable to have a more effective, prolonged and persistent effect.

Barrier function and immune responses can also be improved by increasing mucin production and secretory immunoglobulins, which have the capability to bind and neutralise toxins in the lumen and mucosa before they can reach the intestinal epithelium.  Nutrients that have been shown to have a positive effect on secretory IgA production and secretion include essential omega fatty acids, glutathione, glycine, phosphatidylcholine, vitamin C, zinc and colostrum.

Conclusion

Although an emerging area of research, there is already much evidence for the existence of a bi-directional ‘gut-lung axis’ and the existence of a common mucosal immune system.  This has consequences clinically and underlines the integrated workings of the human body.  It’s becoming clearer that the gut microbiome plays an important role in maintaining immune homeostasis in many distal organs and needs to be considered in all imbalances.  Strategies to maximise its functioning include improving diets to increase SCFA production, targeting beneficial microbial compositions with probiotics, prebiotics and polyphenols, and using nutrients to boost secretory IgA levels and mucin production for improved barrier function.  With the emergence of COVID-19, we can expect to see an increased research focus on the ‘gut-lung axis’ in the coming years.

Karen Jones is a practising BANT Registered Nutritional Therapist in London, having completed her diploma at the College of Naturopathic Medicine (CNM) in 2018, which she followed with a 9 month intensive period of study reviewing the emerging evidence into the microbiome under the guidance of Adam Greer, the most senior nutrition lecturer at CNM. Karen also has a first class degree in Ayurvedic Studies and spent time in India working in an Ayurvedic Clinic. She offers education and practitioner support to Microbiome Labs UK.  Contact her on [email protected]

Microbiome Labs UK is part of TMC Ventures, the sole distributor of its products in the UK, providing nutritional supplements focused on digestive health available exclusively to qualified healthcare practitioners and their clients. Find out about their Total Gut Restoration programme using MegaSporeBiotic, MegaPrebiotic and MegaMucosa.

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References

Anand, S. & Mande, S. (2018) Diet, Microbiota and Gut-Lung Connection. Frontiers in Microbiology. [Online] 9.

Dang, A. & Marsland, B. (2019) Microbes, metabolites, and the gut–lung axis. Mucosal Immunology. [Online] 12 (4), 843-850.

Enaud, R. et al. (2020) The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Frontiers in Cellular and Infection Microbiology. [Online] 10.

Gagliardi, A. et al. (2018) Rebuilding the Gut Microbiota Ecosystem. International Journal of Environmental Research and Public Health. [Online] 15 (8), 1679.

He, Y. et al. (2016) Gut–lung axis: The microbial contributions and clinical implications. Critical Reviews in Microbiology. [Online] 43 (1), 81-95.

Jayachandran, M. et al. (2017) A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota. International Journal of Molecular Sciences. [Online] 18 (9), 1934.

McFarlin, B. et al. (2017) Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World Journal of Gastrointestinal Pathophysiology. [Online] 8 (3), 117.