Gut-Lung Connection - An Overview

Introduction

The human body harbors trillions of microorganisms. They play an important role in human health by modulating innate immunity. The gut houses immense microbes (microbiota), which are considered an “essential organ.” The gut microbiota helps in assimilating dietary nutrients, and they produce metabolites. These metabolites are essential for regulating gastrointestinal immunity. Any disturbance in gut microbiota has a potent impact on distant organs like the lungs, brain, mouth, liver, vagina, etc. Therefore, a high-nutrient diet is essential for maintaining gut microbiota.

What Are Gut Microbiota?

Major microbiota in the gut are the Firmicutes (e.g., Lactobacillus, Bacillus, and Clostridium) and the Bacteroidetes (e.g., Bacteroides). Proteobacteria (e.g., Escherichia) and Actinobacteria (e.g., Bifidobacterium), Cyanobacteria, and Fusobacteria are also present to some extent. Species of Fungi (Saccharomyces cerevisiae, Malassezia restricta, and Candida albicans) have also been recognized in some individuals. Yeasts (Saccharomyces boulardii) also inactivate intestinal pathogens.

What Is the Role of Gut Microbiota on the Gut?

The gut microbiota ferments dietary fibers and intestinal mucus to produce short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate.

• Butyrate destroys colon cancer cells and balances glucose and energy.

• Acetate plays a role in cholesterol metabolism and appetite regulation.

• Propionate regulates glucose production.

What Are the Lung Microbiota?

The lung harbors the same Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria. Environmental fungi Ascomycota (Aspergillus, Cladosporium, Eremothecium, and Vanderwaltozyma) and Microsporidia (Systenostrema) have also been identified.

What Is the Role of the Lung Microbiota on Lungs?

Lung microbiota act with the lung immune cells (alveolar macrophages and dendritic cells) to initiate immune responses against pathogens. They also play a role in immune tolerance.

What Is a Gut-Lung Connection?

The lungs and the gut communicate through the chemical messengers produced by the microbiota. This connection is called the gut-lung axis. The gut microbiota breaks down food particles and produces metabolites (short-chain fatty acids). The SCFAs travel throughout the body via blood and lymph to influence immune cell recruitment, thereby reducing inflammation in organs, including the lungs. Microbiota also produce messengers like endotoxins that trigger immune cells to produce cytokines. Cytokines are protein molecules that promote inflammation. This shows that a healthy gut prevents inflammation, whereas an unhealthy gut provokes inflammation. The gut and the lungs host similar messengers; changes in the intestinal microbiota have a significant impact on lung diseases, and changes in the lung microbiota have a profound effect on the gut. The imbalance in the microbiota is called dysbiosis.

How Does Gut Microbiota Impact Lung Diseases?

The gut microbiota resists the colonization of pathogens. The gut dysbiosis caused by antibiotics destroys some or more intestinal microbiota, increases the susceptibility to enteric infections caused by Salmonella and Escherichia coli, and impairs response to systemic and respiratory infections caused by the Influenza virus and the respiratory syncytial virus.

Dysbiosis of the normal gut microbiota induces the development of various respiratory disorders.

• Low levels of gut microbiota (Akkermansia muciniphila and Faecalibacterium prausnitzii) are associated with low levels of metabolites that are essential for protection against environmental immunity. This dysbiosis makes the individual more susceptible to allergens thereby causing asthma.

• Dietary fiber enhances the activity of gut microbiota to produce SCFAs.This modulates innate immune response and inflammation, maintains epithelial integrity, and prevents microbial invasion. Dysbiosis in this mechanism induces COPD.

• In tuberculosis, the synthesis of butyrate and propionate was found to be decreased. Gut dysbiosis reduces the activation of the immune response against Mycobacterium tuberculosis and results in tuberculosis infection.

• Segmented filamentous bacteria in the gut stimulate inflammatory neutrophils and offer protection against pneumonia.

• Bacteroides species reduce inflammation. Reduction in this influences inflammation in cystic fibrosis.

• Increased levels of Enterococcus species and decreased levels of Bifidobacterium are associated with lung cancer.

What Is the Gut-lung Axis Concept?

The gut-lung axis concept postulated that any changes in the intestinal microbiota communities may have a significant effect on lung disease. It was thought that the microbes may be recognized by the immune cells of the host. This leads to the release of systemic cytokines. In some of the cases, the bioactive materials are released from the microbes. These materials or compounds enter the bloodstream and become responsible for the alteration of lung function.

What Is the Importance of the Connection Between Intestinal Fungal Dysbiosis and Asthma?

Every person has a separate or particular microbiota composition. When these microbial communities exhibit a negative effect on the lung disease, is called dysbiosis. Dysbiosis is not the same as intestinal infection. Dysbiosis differs from intestinal infection in such a way that it can occur silently for many years without any symptoms.

Apart from bacteria, the intestine contains communities of commensal fungi. Many fungi that are linked to asthma-like aspergillus, penicillium, or Alternaria, can be found in human intestinal mycobiota.

Research done in 2018 has shown that intestinal fungal dysbiosis can increase the severity of asthma in animal models. When an expansion of dysbiosis fungi occurs in the intestine, it increases the severity of asthma without any fungus in the lungs. This is suggestive of gut-lung axis cross-talk between the intestines and lungs. The effect is not for all species of fungi. This means that some fungi may make asthmatic inflammation worse, some may not have any effect, or some may be protective.

The increased use of antibiotics may cause fungal dysbiosis by disrupting bacterial communities.

What Is the Composition of a Healthy Lung Microbiome?

The microbiome involves all the microbes in a specific habitat at a specific time. The composition of microbes varies depending on the state of the lungs. Lungs contain the dominant phyla, which include Firmicutes and Bacteroidetes, and the main bacterial genera are Prevotella, Porobacteria, and Streptococcus.

A healthy microbiome consists of a complex and diverse bacterial community. These are with a low biomass of only 103 to 105 bacteria per gram of tissue.

What Is the Impact of Lung Microbiota on the Gut?

Dysbiosis in the lung microbiota moves the lung bacteria into the intestine via blood, increases the bacterial load in the intestine, and disturbs the gut microbiota.

• Influenza virus infection increases Enterobacteriaceae and reduces Lactobacilli and Lactococci in the gut microbiota.

• Pneumonia caused by Pseudomonas aeruginosa induces intestinal injury.

What Is the Role of Diet in the Gut-Lung Axis?

A fiber-rich diet is essential for producing significant metabolites and maintaining human health. The gut microbiota breakdown of dietary fibers increases the production of SCFAs and lowers the gut pH, thereby reducing the colonization of pathogens.

• Clostridium orbiscindens breaks down plant flavonoids to produce desaminotyrosine. This travels to the lungs via the blood and influences the immune system to protect from influenza infection.

• Fermentation of inulin fiber by gut bacteria offers protection against influenza infection.

• Fermentation of pectin fiber protects against Respiratory syncytial virus.

Nutrients are utilized by gut microbiota to produce metabolites to regulate the immune system. Therefore, diet directly influences intestinal microbes in maintaining human health.

What Is the Role of Probiotics?

Probiotics are live; good microbes are present in yogurt, fermented foods, and dietary supplements.

• The administration of probiotic bacteria like Lactobacillus casei Shirota or rhamnosus reduces symptoms of cystic fibrosis.

• Lactobacillus rhamnosus and Bifidobacterium breve reduce inflammation caused by cigarette smoke, thereby reducing diseases like COPD.

• Probiotics enhance intestinal barrier function against lipopolysaccharides and improve inflammatory conditions such as inflammatory bowel disease, allergy, COPD, and asthma.

• Enterococcus hirae and Barnesiella intestine hominins are administered to cancer patients to improve the efficacy of cancer treatments.

What Is the Role of Prebiotics?

Prebiotics are plant fibers that are essential for the growth of good bacteria in the gut. Fibrous fruits and vegetables contain prebiotics. These complex fibers are indigestible; they pass through the digestive tract and become food for the bacteria. So prebiotics are important to promote the growth of good bacteria.

Conclusion

The gut and the lung are two distant organs in the human body. They communicate through the microbial community. Good gut health is essential for maintaining the vital functions of all organs. In addition, the gut microbiota is significant in the defense mechanism. Consumption of prebiotics and probiotics through a fiber-rich diet helps in the preventive and therapeutic interventions against pathogens.