The Gut-Lung Axis: Microbial Niches and Their Impact on Pulmonary Health
Respiratory conditions, both chronic and acute, are some of the most common issues seen in clinical practice. In 2016, chronic obstructive pulmonary disease (COPD) alone accounted for around three million deaths and was the third leading cause of death worldwide.1 Asthma is one of the most common chronic diseases, globally affecting nearly eight percent of people (over 24 million) in the US alone. Childhood onset of asthma can impair airway development, and persist into adulthood. Adult asthma may accelerate the decline of pulmonary function, and increase susceptibility to infection. Both children and adults with severe asthma have impaired innate antiviral immunity with altered cytokine responses, and increased risk of hospitalization—an issue of particular concern currently. Comorbid conditions are common, with almost two-thirds of
those with asthma having at least one comorbidity. The most common comorbidities are diabetes, osteoporosis, metabolic syndrome, cardiovascular disease, and mental illnesses.2 Lower respiratory infections were the fifth leading cause of death and the leading cause of infectious death globally in 2015.3
With the prevalence of both chronic and acute respiratory illnesses, it is in the best interest of our patients to identify and address root cause and practice prevention. A growing body of evidence has highlighted the influence of the gut microbiota on lung immunity—the Gut-Lung Axis—and current research has drawn a strong correlation between dysbiosis of several anatomical areas and pulmonary health or disease. Here is a synopsis of current research focusing on the microbiome, the Gut-Lung Axis, and their roles in pulmonary health.
- Every chronic lung condition exhibits an altered pulmonary microbiome. Until recent years, the lungs were thought to be sterile, which has been proven untrue. In fact, pulmonary health can be predicted by the presence of healthy microorganisms. Asthma, COPD, pneumonia, cystic fibrosis, and all other chronic lung diseases have an unhealthy balance of beneficial and pathogenic organisms.4
- The microbiome influences the host immune system. Beneficial microorganisms in the gastrointestinal tract assist in the development of healthy immune function including defense through regulation of T cells, systemic inflammation, and tolerance. Pathogenic organisms contribute to immune imbalances and a shift toward allergy and autoimmunity.5 6
- Immune cells in the lungs recruit from primed immune cells in the gastrointestinal (GI) lymphatics. In an illustration of the complexity and beauty of human physiology, when the sinuses, mouth, and throat are exposed to pathogens, the bugs are swallowed and read by the lymphatics in the gut (gut-associated lymphoid tissue, or GALT). They then produce an artillery of defenses just in case infection occurs. When it does, the immune system in the lung actively recruits those defenses to fend off illness.5
- The gut and lung microbiota contribute to exacerbations of lung disease. Gastrointestinal dysbiosis can contribute to oral and pulmonary dysbiosis, all of which can result in exacerbations of lung disease.5 One study reported that more than 70 percent of people with severe lung disease also have gastroesophageal reflux disease (GERD), a common association with GI dysbiosis.7
- The microbiome of the lung is most closely associated with the oral microbiome. During sleep, microaspiration of saliva occurs, resulting in the transfer of microorganisms from the mouth to the lungs. Since plaque and periodontal pockets are sources of microorganisms, oral hygiene and the oral microbiome need to be tended as well.8
- The gut microbiota contributes to acute lung injury. Bacterial metabolites, such as lipopolysaccharides (LPS), mediate systemic inflammation and tissue injury via stimulation of toll-like receptor 4 (TLR4) receptors. Reducing endotoxins via modulating the microbiome can assist in maintaining a balanced immune/inflammatory response, allowing for immunity that protects—but is regulated—to prevent damage.5
- The vagus nerve is involved. When the vagus nerve is sending healthy signals, it prevents shock-induced organ injury (including in the lungs) and prevents injury of the gut barrier.59
- Beneficial microorganisms reduce systemic inflammation. Production of short-chain fatty acids (such as butyrate and acetate) by beneficial bacteria helps to reduce inflammation throughout the whole body, establishing balanced and effective immune activity .6
It is clear that targeting the microbiome may benefit overall health, including the lungs. Providing support to the gastrointestinal microbiome is important, and it is also vital to remember the influence of the oral microbiome on the gastrointestinal microbiome. Research shows that organisms that exist in the mouth can translocate to the gut, and cause dysbiosis there.
5 https://www.tandfonline.com/doi/full/10.1080/1040841X.2016.1176988
6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595839/
7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751994/pdf/nihms756902.pdf
8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751994/pdf/nihms756902.pdf
9 https://journals.physiology.org/doi/full/10.1152/ajpgi.00412.2001
Additionally, since the pulmonary microbiome is most closely related to that of the mouth, if left untreated and unbalanced, the oral microbiome may be a source of persistent illness in the lungs and the GI tract. Furthermore. direct translocation of pathogens from the mouth to systemic blood-flow can occur, resulting in damage to the lungs and other organs.
“Less than 1 minute after an oral procedure, organisms from the infected site may have reached the heart, lungs, and peripheral blood capillary system.”10
As clinicians, we are always on the lookout for clinically effective products and practices. Botanicals offer well-tolerated and effective options. Virtually all botanicals carry multiple activities in the body. Herbal medicines have been utilized in the treatment of infection for thousands of years, and provide a safe and effective option for addressing biofilms and dysbiosis, while simultaneously supporting a healthy immune response. Using the properties of more than one botanical in a combination or formula provides a broader spectrum of activity against multiple classes of organisms. The resulting formulations, or “biocidal combinations,” are powerful allies that may be used to address infection.
Botanicals are Effective Against Biofilms and Planktonic Organisms
Botanicals accomplish the control of biofilms through several methods. One is by the inhibition of quorum sensing. Quorum sensing is cell signaling by bacteria and other organisms using autoinducers to determine gene expression, virulence, resistance, and development of biofilms. Botanicals shown to inhibit quorum sensing, such as Garlic and Oregano, are well-known for their antimicrobial ability. This new understanding of how they can combat biofilms highlights their clinical and historical significance.
Another method of biofilm control is the inhibition of efflux pumps within cells called multidrug resistance pumps. Plants containing tannins, berberine, and certain phenolics have useful effects as efflux pump inhibitors, demonstrating marked synergy when combined with conventional antibiotics against a variety of both Gram-positive and Gram-negative organisms. Goldenseal, Black Walnut, White Willow, Raspberry Leaf, and Garlic are a few that have been studied.
Bacteriostatic agents inhibit the reproduction of biofilm organisms and so help to control the spread of infection. Berberine has been proven bacteriostatic for Staphylococcus epidermidis. One study showed that sub-minimal inhibitory concentrations blocked the formation of S. epidermidis biofilms. Both Gentian and Goldenseal contain berberine and are particularly useful additions to the biocidal combination for biofilm control. Grapeseed and Bilberry contain condensed tannins that prevent adherence of biofilms and may inhibit swarming.
One study, performed at the University of Binghamton in 2013, shows the complete eradication of biofilms and remarkable broad-spectrum activity with exposure to a biocidal formula containing Bilberry extract, Noni extract, Milk Thistle, Echinacea (Purpurea extract and Angustifolia), Goldenseal, Shiitake extract, White Willow Bark, Garlic, Grapeseed extract, Black Walnut (hull and leaf), Raspberry, Fumitory extract, Gentian, Tea Tree oil, Galbanum oil, Lavender oil, and Oregano oil. This botanical combination was tested on both planktonic organisms and biofilm communities. Pathogens including pseudomonas, E. coli, and Candida albicans biofilms were eliminated in a matter of hours and did not recur.
Botanicals in Oral Infection
Botanicals have a long history of use for oral health. A recent pilot study illustrates the potential of a liposomal botanical formula to significantly reduce pathogen load. In this study, 35 pathogens were detected, followed by one month of treatment with the botanical formula. The result can be seen below, with the bacteria reduced to four remaining pathogens. The study showed clearance of bacterial, viral, amoeba, and fungal pathogens.
“The Liposomal botanicals used in our study appear to be a wonderful adjunct in the treatment of periodontal disease. This statement is based on actual controlled pilot studies that I have performed clinically in my office. The periodontal study was utilizing classic clinical periodontal parameter and phase-contrast microscopy. Based on these studies, I am using these as an adjunct in my office every day and would highly recommend them."
—John A. Rothchild, DDS, FAGD, MAGD, DAAPM, NMD, IMD
There is a wealth of data available definitively demonstrating the usefulness of botanicals as a safe and effective strategy addressing bacterial, viral, and fungal infections. Used correctly, the wealth of the plant kingdom is one of our greatest allies in optimizing our health and provides a strong defense against infectious diseases. Botanicals offer a novel approach for supporting immune function both by balancing the various microbiota and by direct modulation of immune activity in the oral and gastrointestinal mucosa.
