The numbers and arrangement of bacterial species are also different in each organ. Generally, a healthy adult human colon has the highest amount of bacteria (10
14), followed by the skin (10
12), dental plaque (10
12), lower intestine (10
11), saliva (10
11), stomach (10
7), duodenum (10
7)
[4], the bloodstream (10
6 to 10
7 per mL), eyes (0.06 bacterium per human cell) (Gomes et al., 2020), and the respiratory system (around 10
4 microorganisms per mL) (Mathieu et al., 2018). Some studies even suggest bacterial cells are present in organs previously known as sterile, such as the brain and blood cells
[5]. Pioneering microbiologist Louis Pasteur once stated that “life without bacteria would be unthinkable”. In fact, humans are considered superorganisms consisting of symbiotic microorganisms and cells
[6]. Undoubtedly, a microorganism plays a significant role in human lives. In addition to dreadful infections, they also represent a crucial component of the human body; these commensal microbes in the body, collectively known as microbiota, are required for vital functions
[7]. In particular, bacteria are a major part of the human microbiota.
Undoubtedly, air pollution is a serious environmental and health concern. According to the WHO’s recent update, air pollution has affected almost all the global population; currently, 99% of people breathe air that exceeds the WHO clean air quality limits. However, the proportion and exposure of air pollution are highest among low- to middle-income nations, especially in Asian countries
[15]. According to the United States Environmental Protection Agency (US EPA), common air pollutants, such as particulate pollutants (PM
2.5, PM
10), sulphur dioxide (SO
2), carbon monoxide (CO), lead (Pb), ozone (O
3), and nitrogen dioxide (NO
2), are the most harmful pollutants to environmental and human health
[16].
2. Air Pollutants and Dysbiosis of Human Microbiota
Alterations in the microbiota can be due to exposure to various environmental factors
[20]. Air pollutants such as particulate matter (PM
0.1, PM
2.5, PM
10), O
3, and polycyclic aromatic hydrocarbon (PAH) inhalation may alter the human microbiota by various pathways, depending on the type of exposure. In particular, there are several courses for air pollutants and gut microbiota interactions. For instance, the gastrointestinal tract may have exposure to air pollutants via inhalation and ingestion. Usually, large particulate pollutants are deposited in the upper airway such as the trachea; but the finer pollutants, such as PM
2.5, reach into the lung’s alveolar space, further moved and hidden by alveolar macrophages
[21][22].
Air pollutants are associated with dysbiosis of the human microbiota, particularly the gastrointestinal microbiota. Air pollutant polycyclic aromatic hydrocarbons (PAH) may alter the commensal as well as environmental microbial communities. Air pollutant PAH can affect the purine pyrimidine metabolites’ signaling pathways and lipid metabolism
[22]. An animal (broilers) study showed ammonia inhalation can also alter tracheal and ileal microbiotas by the TLR4 signaling pathway
[23].
Studies showed that high concentrations of inhaled particulate matter are transported through the mucociliary pathway and that the pollutant is rapidly cleared from the lung’s alveolar cells but further transported to the intestine. Ingested particulate matter triggered gastrointestinal inflammation-induced dysbiosis of gut microbes
[24]. Gut microbiota dysbiosis causes several health issues including mental health via the gut-brain axis. Gut microbes can influence the central nervous system via the vagus nerve
[25][26]. Particulate matter (PM) and heavy metal air pollutants are exposed to the gut via inhalation or ingestion. PMs cause gut dysbiosis, which further disturbs or alters the composition of gut microbiota-associated regulatory metabolites such as short-chain fatty acid (SCFA), which is required for brain-gut neurotransmitter signals
[27].
Short-chain fatty acid (SCFA) is the predominant anion and is usually produced by the commensal gut bacterial fermentation of undigested carbohydrates. Interestingly, up to 95% of SCFA is absorbed by colon cells (colonocytes) as an energy substrate. Colonocytes usually derive their energy (up to 70%) from SCFA’s oxidation, which provides nearly 10% of the daily calories required for the human body.
Most studies focused on gut microbiota dysbiosis, due to its role in several diseases and since the gut microbiota is associated with various ailments and may influence host cognitive function and behavior by communicating altered signals to the hypothalamus–pituitary–adrenal (HPA) axis
[20].
Figure 2 shows a possible mechanism of air pollution associated with dysbiosis of gut microbiota and health issues.
Figure 2. A possible mechanism of air pollution associated gut microbiota dysbiosis and health issues: (1) air pollutant entry; (2) respiratory system response; (3) reached to gastrointestinal tract and adsorbed; (4) dysbiosis and alteration of commensal gut microbiota; (5) altered microbial cells and their metabolites increased gut permeability and susceptibility to pathogens; (6) infiltration of harmful metabolites and pathogens decrease gut microbiota-dependent metabolites such as short-chain fatty acid (SCFA); (7) disturbed gut-brain axis (GBA) and hypothalamus–pituitary–adrenal axis (HPA); (8) altered signaling metabolites influence several organs’ functionalities.
Another proposed mechanism explains how ingested pollutants enter and are further adsorbed into the intestine from the bloodstream. These pollutants are also oxidized into the liver, form conjugates such as glutathione, and are excreted into the intestine again. The gut microbiota interferes with normal glutathione secretion; gut microbes additionally metabolize those pollutants, which disturb their composition as well, which could be responsible for the inactivation or re-activation of the specific metabolites or compounds responsible for various associated health conditions including cancer
[28]. Certain commensal bacterial species such as
Escherichia coli also turn invasive and cause metabolic endotoxemia, which increases the permeability of the gut wall, decreases mucus thickness, and allows pathogenic invasive bacterial species to infiltrate
[29].
Studies have suggested air pollution’s negative impact on human microbiome development, which is associated with serious health outcomes including obesity, gastric ailments, and autism. Up to this time, air pollution garnered less attention despite the potential risk of negative alterations
[8][30].
Several studies have explained gut microbiota dysbiosis; however, it is a multifactorially dependent, complex event to understand clearly, so far. More comprehensive research is required to understand air pollutant exposure associated with microbiota dysbiosis, especially to explain the other microbiotas’ dysbiosis of the human body.
3. Air Pollution Impact on Nasal Microbiota
The human nasal tract is the home of diverse bacterial communities. Nasal microbiota plays a pivotal role in personal and public health as well. Human nostrils are colonized by various microbes just after birth. Usually, pediatric and adult nasal microbiotas are distinguished from each other. Pediatric nasal microbiota usually belongs to the Gram-negative bacteria Haemophilus and Moraxella and Gram-positive bacteria Streptococcus, Staphylococcus, Dolosigranulum, and Corynebacterium. In the case of adults, the nasal microbiota is mostly Gram-positive (Firmicutes and Actinobacteria). Despite ample exposure to oxygen, the most frequent nasal bacterial species are either facultative anaerobes or aerotolerant. There are lesser-known factors that influence and alter nasal microbiota; age, season, and climate may also alter the nasal microbiota
[31]. Additionally, air pollution, even low exposure, may influence the nasal microbiota during the first year of life; especially, exposure to air pollutants PM
2.5 and NO
2 is associated with nasal microbiota alteration, respiratory infections, and asthma development during early life
[32][33].
Nasal microbiota is different from the upper respiratory tract (URT). The upper respiratory tract has constant airflow, which prevents the spread of pathogens to the lower respiratory tract. Usually, the nasal microbiota remains almost unchanged in adulthood. A few studies suggested that the nasal microbiota has been significantly associated with the central nervous system and immune system. Dysbiosis in the nasal microbiota may lead to inflammatory diseases and pathological invasion of the nasal cavity, which may damage the olfactory system
[34].
The altered composition of beneficial bacteria residing in the nasal sinus cavity was found to be associated with Parkinson’s disease
[35]. Growing evidence suggests that particulate air pollutants (PM
2.5, PM
10) may alter the nasal bacterial community
[36][37].
4. Air Pollution and Oral Microbiota Dysbiosis
A balanced, normal composition of oral microbiota is required for the oral and probably overall health of the host. Being a compatible environment, the oral cavity facilitates the growth of many distinct commensal as well as harmful microbes. In recent years, the importance of the oral microbiome has also increased in dental medicine. The oral cavity is susceptible to constant environmental factors including host eating habits, saliva secretion, mastication, and exposure to outside microbes
[38][39]. Air pollutants such as ultrafine particles (PM
0.1) can affect the oral microflora and promote inflammation in the oral cavity of children
[40].
In 2010, research highlighted the importance of the oral microbiome for the first time. Most recently, oral microbiota dysbiosis has emerged as one of the contributing factors to diseases such as schizophrenia and osteoporosis. Until now, probiotics were found to be useful for the restoration of oral dysbiosis
[41]. Similarly, several molecules from saliva form a specific film to minimize dysbiosis; therefore, the process of dysbiosis may increase if the amount of saliva decreases
[42].
Oral microbiota may influence other distant organs. Altered oral microbiota can disseminate to other organs via ingestion and systemic circulation. Recent findings indicate an association between altered oral microbiota and liver and pancreatic diseases
[43], oral cancer
[44], and Alzheimer’s disease
[45]. A recent metagenomic analysis revealed that oropharyngeal microbiota dysbiosis was linked with COVID-19 severity
[46]. In addition, oral and gut microbiotas’ crosstalk may increase the complication of oral dysbiosis to other organs
[47].
5. Air Pollution Impact on Pharyngeal Microbiota
The pharyngeal microbial communities are important in the airflow cavity to stimulate the immune system and prevent unwanted pathogenesis of airborne germs. These local microbes provide a defense line against newly emerging pathogens. The most common pharyngeal microbiota belongs to bacterial genera such as
Campylobacter,
Capnocytophaga,
Haemophilus,
Neisseria,
Streptococcus,
Prevotella, and
Veillonella. To retain proper health, a balance of common microbiota is necessary for all. However, the epithelial microbial community in the pharynx can be damaged by factors such as air pollutants, smoking, and infections
[48].
It has been reported that even a few days of exposure to particulate air pollutants may alter the pharyngeal microbiota composition, which can increase the chance of respiratory infections
[49]. A similar study in China concluded that air pollution can lead to oropharyngeal microbiota dysbiosis. The microbial population may differ as per the air pollutants’ concentration. For instance, in most polluted regions, bacteria belonging to
Fusobacteria and
Bacteroidetes were significantly lower while others, such as Proteobacteria,
Firmicutes, and
Actinobacteria, were found to be higher in participants
[50].
A recent experiment analyzed the nature and characteristics of pharyngeal bacteria among chronic pharyngitis patients using 16S rDNA-based detection technology. The study concluded that the community and quantity of symbiotic pharyngeal bacteria decreased while the number of opportunistic bacteria increased in chronic pharyngitis patients
[51]. Pharyngeal microbiota’s abundance and specificity have also been associated with age-related macular degeneration
[52].
The pharynx microbiota’s potential role between gut and lung crosstalk is being investigated. A clinical study on neonates’ pharynx and intestine microbiotas showed a significant difference between intestinal and pharynx microbial species and composition. However, some species such as Streptococcus were common in both
[53].
6. Air Pollution and Altered Respiratory Microbiota
The respiratory system is a complex system that facilitates oxygen and carbon dioxide exchange. Nostrils of the lungs and alveoli of the human respiratory system are inhabited by specific bacteria, which are known as the common microbiota of the respiratory tract and work as a gatekeeper to prevent the colonization of pathogens. Respiratory microbiota also maintains respiratory physiology and immunity. Despite the respiratory microbiota’s important role in mediating human health response to inhaled irritants, the respiratory microbiome and inhaled pollutants’ association have remained less explored
[54].
Healthy lung microbiota usually belongs to
Firmicutes and
Bacteroidetes. Alteration of the respiratory microbiome is associated with inflammation and chronic lung diseases. Polluted air introduces a mixture of air pollutants such as PM
2.5, PM
10, O
3, NO
2, CO, SO
2, polycyclic aromatic hydrocarbons, and pathogens into the respiratory system. The effect of polluted air is bidirectional, as air pollutants such as PM
2.5 penetrate deeply into lung cells and damage epithelial integrity, which further facilitates the entrance of harmful microbes and toxic metabolites into the epithelial layer and triggers systemic immune activation, which causes alteration or dysbiosis of the lung microbiota. Air pollutants also provoke the production of reactive oxygen species (ROS), which directly kills and reduces the resident microbiota
[55].
A study on 40 children showed that exposure to automobile air pollution in childhood and adolescence may be associated with significant changes in the lower respiratory microbiota, which may lead to asthma. Alteration and dysbiosis of the respiratory microbiota can increase the chance of lower and upper respiratory tract infections. In particular, lower respiratory infection such as pneumonia is responsible for considerable morbidity and mortality among children under 5 years globally
[56]. A cross-sectional study on healthy adults in Malawi showed that higher exposure to particulate air pollutants caused an abundance of the potentially pathogenic bacteria Streptococcus and Neisseria in their lungs
[57]. Therefore, air pollution can affect the respiratory microbiota and induce dysbiosis, which is associated with several respiratory diseases
[58].