Environmental dust and NCDs

The Urban Environment and Childhood Asthma (URECA) birth cohort examined a high risk cohort (n = 560) from the cities Baltimore, Boston, New York City, and St. Louis and found that reduced richness and diversity in house dust bacteria during the first year may be associated with atopy and its recurrent risk at age of 3 years.^{Reference Lynch, Wood and Boushey36} Higher exposure to specific Bacteroidetes and Firmicutes was protective against atopy and recurrent wheezing, and these bacterial taxa were correlated with the levels of allergens. Longer follow-up of this cohort also showed the distinct differences between the early life household microbiota of participants that subsequently develop asthma at 7 years of age and those that did not. Abundance of specific taxa including Staphylococcus, Haemophilus (Pasturellaceae), Corynebacterium, and some Sphingomonas members were elevated in houses of children who subsequently developed asthma.^{Reference O’Connor, Lynch and Bloomberg16} Additionally, low microbial richness of household dust was correlated with high wheeze and high atopy phenotypes, while high microbial richness of household dust was correlated with transient wheeze and low atopy phenotypes.^{Reference Bacharier, Beigelman and Calatroni37} Taken together, these findings suggest that concomitant exposure to higher amount of allergen and house dust bacterial content may protect against and potentially alleviate atopy and recurrent wheezing.^{Reference Lynch, Wood and Boushey36} Similarly, based on the findings from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study, our group has reported that there were differential microbiota and allergen profiles in house dust collected from homes of allergic participants compared to healthy controls.^{Reference Loo, Chew and Zulkifli38} Houses of allergic participants had higher levels of Bacteroidaceae, Anaplasmataceae, and Leptospiraceae, all of which are gram negative.^{Reference Loo, Chew and Zulkifli38} Endotoxins which are associated with gram negative bacteria have also been shown to potentially increase risk of wheezing in children from a Boston study.^{Reference Park, Gold, Spiegelman, Burge and Milton39} Besides this, abundance of Bacteroidaceae was higher in gut microbiota of allergic Japanese subjects at 1 and 2 months of age, as compared to the non-allergic subjects which also suggests a possible link between environmental and gut microbiota.^{Reference Songjinda, Nakayama and Tateyama40} As part of the Karelian Allergy Study, dust samples from Finnish and Russian Karelia homes were analyzed;^{Reference Pakarinen, Hyvarinen and Salkinoja-Salonen41} although the Finnish and Russian Karelia children are genetically similar, they had contrasting prevalence of atopy and marked differences in household dust microbial composition. In the Russian Karelian homes, atopy risk was low and Staphylococcaceae followed by Actinobacteria and Firmicutes were the most abundant bacteria in dust. In contrast, the Finnish Karelian homes had a high atopy risk associated with a higher prevalence of Proteobacteria, and lower abundance of Staphylococci and Corynebacterium. The data suggested that the microbial composition of house dust may be closely associated with allergic outcomes.

To our knowledge, there are currently no studies that have examined the direct relationships between the dust microbiome and metabolic conditions such as obesity and diabetes. However, there are observational studies that have reported associations between air pollution and metabolic diseases. Ambient air pollution refers to a vast array of pollutants including PM_2.5, PM₁₀, and TRAP.^{Reference Metzger, Tolbert and Klein42} TRAP comprises of nitrogen oxides, PM, carbon dioxide, hydrocarbons, and carbon monoxide, and also other emissions unrelated to combustion such as tyre wear.^{Reference Matz, Egyed, Hocking, Seenundun, Charman and Edmonds43} Diesel exhaust is also one of the major components of TRAP and contributes extensively to PM_2.5.^{Reference Costa, Cole, Coburn, Chang, Dao and Roqué44} Emergency department visits for cardiovascular diseases was found to be correlated with pollutants present in ambient air pollution,^{Reference Metzger, Tolbert and Klein42} and a higher exposure to TRAP was shown to be associated with a higher rate of asthma readmission in white children compared to African American.^{Reference Newman, Ryan, Huang, Beck, Sauers and Kahn45} In a longitudinal prospective cohort of 4550 Southern California children who were aged 5–7 years, exposure to TRAP was positively correlated with increase in BMI after adjustment for parental education, language, measures of green cover in a 500 m radius of the home, and recreational activities in a 5 km radius of the home.^{Reference Jerrett, McConnell and Wolch46} Another study in New York reported that children of mothers with higher prenatal exposure to polycyclic aromatic hydrocarbon as assessed with a personal ambient air monitor had higher BMI and greater obesity risk at 5 and 7 years of age.^{Reference Rundle, Hoepner and Hassoun47} Exposure to ambient air pollution and TRAP was associated with parameters of glucose homeostasis and insulin resistance, e.g., higher fasting glucose, higher fasting insulin, and higher HOMA-IR in children and adolescents.^{Reference Toledo-Corral, Alderete and Habre48} Reduced insulin sensitivity and higher BMI were also observed in a longitudinal cohort of children who were exposed to ambient air pollution with increased PM.^{Reference Alderete, Habre and Toledo-Corral49} Thiering et al. examined the association between long-term exposure to TRAP and insulin resistance in 10-year-old children who were part of two separate birth cohort studies.^{Reference Thiering, Cyrys and Kratzsch50} The group reported that exposure to higher levels of TRAP including PM₁₀ over a period of 10 years caused increased risk of insulin resistance in children.^{Reference Thiering, Cyrys and Kratzsch50} Findings from the Heinz Nixdorf Recall study also reported that traffic-related PM exposure was associated with a higher incidence of T2D in the general population.^{Reference Weinmayr, Hennig and Fuks51} Taken together, the evaluation of dust bacterial content may allow us to delineate the relationship between air pollution and metabolic diseases. The study demographics, pollutant types, and effect of air pollution on human health are summarized in Table 1.

Table 1.

Summary and comparison of studies involving air pollutants and related health outcomes

PM, particulate matter; NO_x, nitrogen oxide; NO₂, nitrogen dioxide; CO, carbon monoxide; TRAP, traffic-relation air pollution; BMI, body mass index; RR, relative risk or risk ratio.

Dust and skin microbiome

The skin is the primary interface with the external environment and is significantly influenced by the biodiversity of the external environment. Skin microbiota not only play a pivotal role in the growth, homeostatic regulation, and development of keratinocytes but also influence host immunity.^{Reference Prescott, Larcombe and Logan52} Hence, factors that affect the composition of the skin microbiome may influence not only the risk of cutaneous disease but also other inflammatory NCDs.

Hanski et al. showed that environmental biodiversity around the surroundings of homes including forests, agricultural land, and species richness of rare native flowering plants was associated with the composition of skin microbiome.^{Reference Hanski, von Hertzen and Fyhrquist53} Atopic 14- to 18-year-old school children from Finland had less environmental biodiversity around the surroundings of their homes, and this was accompanied by lower generic diversity of Gammaproteobacteria on their skin.^{Reference Hanski, von Hertzen and Fyhrquist53} After assessment of the peripheral blood mononuclear cells by real-time quantitative PCR analysis, positive correlation between Gammaproteobacteria and IL-10, an anti-inflammatory cytokine was also found in healthy subjects.^{Reference Hanski, von Hertzen and Fyhrquist53} Hence, the results suggest that environmental factors may impact the skin microbiome and subsequent immune responses, which may play a role in the development of atopic conditions. However, there is a paucity of studies that have examined and compared the association between environmental dust and skin microbiome. Tang et al. reported the presence of commensal human skin bacteria in house dust samples.^{Reference Tang, Chang, Srinivasan, Mathaba, Harnett and Stewart54} Similarly, Hanson et al. found that Firmicutes and Actinobacteria made up the dominant phyla in indoor dust.^{Reference Hanson, Zhou and Bautista55} These bacteria were also found in resident skin flora,^{Reference Hanson, Zhou and Bautista55–Reference Lange-Asschenfeldt, Marenbach and Lang57} pointing to interactions between the dust and skin microbiome.

The development of allergic diseases has been linked to urbanization that caused loss of critical house dust microbes commonly found in the farm setting.^{Reference Robinson, Baumann and Romero58,Reference Rodriguez, Vaca and Oviedo59} Kirjavainen et al. reported a distinct microbiota profile in dust samples collected from 399 rural farm homes with livestock compared to 298 rural non-farm homes in Finland.^{Reference Kirjavainen, Karvonen and Adams60} The farm home dust microbiome was enriched with members of Bacteroidales, Clostridiales, and Lactobacillales orders, and rumen-associated archaea of the Methanobrevibacter genus but had lower abundance of human-associated bacteria, including members of the Streptococcaceae family and Staphylococcus genus. The authors then studied the house dust microbiome in an independent group of 1031 children and found that children living in non-farm homes with house dust microbiota similar to that of rural farm homes had lower risk of asthma.^{Reference Kirjavainen, Karvonen and Adams60} The prevalence of T2D was also lower in individuals living on farm from rural Saskatchewan, Canada compared to individuals living on non-farm locations, and non-farm dwelling remains a risk predictor for diabetes after correcting for known diabetic risk factors e.g. BMI and family history of diabetes.^{Reference Dyck, Karunanayake and Pahwa61} These findings suggest that changes in human microbiome associated with farm and non-farm environments may result from differences in environmental dust microbial profiles, which may have an effect on the development of NCDs.

In a study of 275 Finnish children aged 2 months to 14 years, the differences in skin microbiome between those living in rural and urban area were analyzed.^{Reference Karkman, Lehtimaki and Ruokolainen62} The authors found that the skin microbiome of children living in urban areas had higher levels of Microlunatus, Humibacillus, Nocardioides, and Friedmaniella, which were associated with a higher prevalence of rhinitis symptoms. Additionally, the authors also reported a higher prevalence of sensitization to inhalant allergens in children from the rural regions.^{Reference Karkman, Lehtimaki and Ruokolainen62}

Skin microbiome dysbiosis was observed in a group of T2D patients who showed higher abundance of Staphylococcus epidermidis compared to controls.^{Reference Thimmappaiah Jagadeesh, Prakash, Karthik Rao and Ramya63} Gardiner et al. found that the skin microbial communities were different between T2D and non-T2D adults, with the skin microbiome of diabetics being less diverse compared to controls.^{Reference Gardiner, Vicaretti and Sparks64} The foot skin microbiome was also found to be predictive of diabetic status.^{Reference Gardiner, Vicaretti and Sparks64} However, the diabetic adults were older and had higher BMI, and these may influence the differential microbiome profile between the diabetic and non-diabetic adults. Obese pregnant women were found to have a different skin microbiome profile as compared to non-obese pregnant women, and the higher pre-operative bacterial biomass on the skin of obese mothers may confer an increased risk of surgical site infection following caesarean delivery.^{Reference Rood, Buhimschi and Jurcisek65}

The effect of environmental exposure on skin microbiome and the dysbiosis of skin microbiome in people with NCDs support a possible role for environmental dust in modulating skin microbiome profiles that are associated with the development of NCDs.

Dust and airway microbiome

The airway microbiome comprises bacteria in the oral, nasal, nasopharyngeal, and lung cavities, with breathing providing an avenue for dust to enter and co-colonize the respiratory tract.^{Reference Dinwiddie, Denson and Kennedy66} Dust inhaled into the airway may then influence and alter the airway microbiome. Mariani et al. reported that PM was inversely correlated with the α-diversity indices of nasal microbiome in a group of 51 healthy subjects exposed to different levels of PM.^{Reference Mariani, Favero and Spinazze67} Birzele et al. analyzed dust samples from the mattresses of 86 European children and compared these with their respective nasal samples.^{Reference Birzele, Depner and Ege68} The authors found that similar bacteria richness was present in both mattress dust and nasal samples with Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes being the dominant phyla in both dust and nasal samples, highlighting the potential link between dust and airway microbiome.^{Reference Birzele, Depner and Ege68} Firmicutes and Bacteroidetes have previously been found to be associated with reduced risk of atopic wheeze in the URECA cohort, with reduced abundances of these bacteria in house dust of subjects who did not develop atopy or recurrent wheeze.^{Reference Lynch, Wood and Boushey36} In another study from Sweden, stool samples of 20 infants with atopic eczema were compared to those from 20 healthy infants.^{Reference Abrahamsson, Jakobsson, Andersson, Björkstén, Engstrand and Jenmalm69} The authors found lower levels of Bacteroidetes and Proteobacteria to be significantly associated with atopic outcomes during the first 2 years of life.^{Reference Abrahamsson, Jakobsson, Andersson, Björkstén, Engstrand and Jenmalm69} It was reported that pig farms harbored higher levels of airborne dust as compared to cow farms, and the nasal microbiota of pig farmers was found to be enriched with the greatest bacterial diversity, followed by that of cow farmers, with non-farmers having the lowest diversity.^{Reference Kraemer, Ramette, Aebi, Oppliger and Hilty70} This distinct microbial fingerprint is speculated to have arisen from the unique environmental exposure.^{Reference Kraemer, Ramette, Aebi, Oppliger and Hilty70} Another study by Shukla et al. comparing 21 dairy farm workers and 18 non-farm office workers revealed that a farming environment was associated with higher bacteria species richness in the nasal microbiome as well as elevated levels of Bacteroidetes.^{Reference Shukla, Ye, Sandberg, Reyes, Fritsche and Keifer71} Interestingly, exposure to a dairy farm environment comprising of hay, livestock, and compost, as opposed to an urban office environment, was associated with a decreased burden of Staphylococcus in the nasal microbiome, which may confer protection against subsequent pathogenesis of acute and chronic diseases.^{Reference Shukla, Ye, Sandberg, Reyes, Fritsche and Keifer71} Direct evidence from an animal study showed that rats exposed to mixture of PM₁, PM_2.5, and PM₁₀ (30 g per exposure) for 4 h, five times weekly, over 4 weeks, had alteration in the composition and diversity of their lung microbiome profiles.^{Reference Li, He, Liao, Zhou, Li and Ran72} The PM exposure also induced higher number of alveolar macrophages with increased phagocytic capacity, higher levels of IgA, and lower levels of IgG, which may in turn affect the adaptive immune response of the lungs towards infection.^{Reference Li, He, Liao, Zhou, Li and Ran72}

In the Copenhagen Prospective Study on Asthma in Children (COPSAC) birth cohort, Andersen et al. investigated the effects of air pollution on occurrences of wheezing in 205 children during the first 3 years of life.^{Reference Andersen, Loft and Ketzel73} They found detrimental effects of air pollution comprising PM₁₀, NO₂, and CO on wheezing symptoms in children. Likewise, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study conducted in the Netherlands, Brauer et al. also demonstrated positive associations between air pollution and development of wheezing and asthma in the first 4 years of life.^{Reference Brauer, Hoek and Smit74}

As part of the airway system, the oral mucosa is often the initial site of contact between barrier immunity and the majority of foreign antigens or commensal microbes, prior to entry into the respiratory and gastrointestinal tracts.^{Reference Moutsopoulos and Konkel75} Infants often ingest dust in greater amounts as compared to adults due to the frequent hand-to-mouth or object-to-mouth transfer.^{Reference Wilson, Jones-Otazo and Petrovic76–Reference Moya and Phillips78} Dust particles function as a vehicle for microorganisms which settle in the oral cavity and saliva during mouth-breathing.^{Reference Morman, Plumlee, Knippertz and Stuut79} The abundance of immunological cells in the oral cavity allows for potent immunological responses to be triggered by the dust-oral microbiome interactions, which may be crucial in the development of NCDs.

Although there is no evidence to support a direct association between dust and the oral microbiome, oral bacteria has been shown to translocate from mouth to gut;^{Reference Olsen and Yamazaki80,Reference Li, Ge and Cheng81} hence an effect of dust on gut microbiome could be mediated by the oral microbiome, itself influenced by the microbial communities present in the dust.

Obese individuals were found to have a lower prevalence of probiotic bacterial taxa including Bifidobacterium and Lactobacillus and a higher prevalence of common bacterial taxa including Firmicutes in their oral cavity as compared to non-obese individuals.^{Reference Yang, Cai and Zheng82} Obese girls showed greater diversity and decreased richness in their oral microbiome profile as compared to non-obese girls.^{Reference Mervish, Hu and Hagan83} Oral microbiome dysbiosis was also reported between age-matched T2D and normal weight non-diabetic men and women.^{Reference Long, Cai and Steinwandel84} Actinobacteria was less abundant in both T2D and obese non-diabetic individuals as compared to normal weight controls, suggesting that oral microbiome may play a role in the etiology of obesity and diabetes.^{Reference Long, Cai and Steinwandel84} The oral microbiome of elderly people with T2D were found to be enriched with potential disease-associated bacterial genera, including Leptotrichia, Staphylococcus, Catonella, and Bulleidia.^{Reference Wang, Xu and Ji85} In a longitudinal study of 188 infants who were followed through the first 7 years of their lives, children who developed allergic diseases or asthma had lower oral bacterial diversity compared to healthy children.^{Reference Dzidic, Abrahamsson, Artacho, Collado, Mira and Jenmalm86} Saliva samples were obtained at 3, 6, 12, 24 months, and 7 years timepoints from 47 allergic children and 33 healthy children. The oral microbial profiles differed between children with allergic diseases or asthma and healthy children throughout the 7 years of follow-up. Oral bacteria including Gemella haemolysans, Prevotella sp., and Streptococcus lactarius were associated with allergy development specifically at the age 7 years timepoint.^{Reference Dzidic, Abrahamsson, Artacho, Collado, Mira and Jenmalm86} These findings suggest a possible role of the oral microbiome in the development of NCDs, with the oral microbiome potentially being influenced by environmental dust.

Dust and gut microbiome

The gut microbiota is host to over 10¹⁴ microorganisms that influence health and disease susceptibility.^{Reference Ley, Peterson and Gordon87} There has been growing evidence implicating gut microbiota dysbiosis in the development of chronic inflammatory disorders such as obesity, diabetes, and allergy.^{Reference Kinross, Darzi and Nicholson88} Hence, understanding the factors that affect gut microbiota composition may provide insights into the pathogenesis of these diseases. A Chinese population-based epidemiological study by Liu et al. reported that exposure to dust particles, PM_2.5 and PM₁₀, was associated with increased risk of T2D and impaired fasting glucose.^{Reference Liu, Chen and Xu89} Dust particles were associated with a reduction in gut microbiota diversity and mediation analysis showed that gut microbiota may partially mediate the association between dust exposure and T2D.^{Reference Liu, Chen and Xu89} TRAP recorded from road traffic sources were shown to correlate with decreased Bacteroidaceae and increased Coriobacteriaceae in the gut microbiome of overweight and obese adolescents, and these gut bacteria also correlated with fasting glucose levels.^{Reference Alderete, Jones and Chen90} Although the study did not compare the effect of TRAP on gut microbiome between obese and non-obese individuals,^{Reference Alderete, Jones and Chen90} TRAP was shown to reduce the abundance of Bacteroidaceae, elsewhere reported to be lower in obese children compared to non-obese children.^{Reference Riva, Borgo and Lassandro91}

In another study by Konya et al., fecal samples were collected from a subset of 20 infants aged 3–4 months recruited under the Canadian Healthy Infant Longitudinal Development (CHILD) study and house dust was also collected from the household of participants.^{Reference Konya, Koster and Maughan92} The collected dust showed a more diversified microbiome as compared to stool microbiome but there was a significant co-occurrence of 14 bacterial operational taxonomic units (OTUs) including Actinobacteria (3), Bacilli (3), Clostridia (6), and Gammaproteobacteria (2) between paired house dust and fecal samples.^{Reference Konya, Koster and Maughan92} Of these, the three OTUs from Actinobacteria comprised of Bifidobacterium spp, which have been previously shown to play an important role in the prevention of atopic outcomes.^{Reference Björkstén, Sepp, Julge, Voor and Mikelsaar93–Reference Zheng, Liang and Wang95}

The findings from human studies suggest that house dust may be a determinant of the gut microbiome in early life, raising the possibility that effects of dust on human health may be modulated through the gut microbiome. However, longitudinal follow-up studies are required to further evaluate the impact of dust exposure on gut microbiome.

Although the existing human studies mainly reported associations between dust and the gut microbiome, studies in animal models have demonstrated a more direct effect of dust on the gut microbiome. Eight- to twelve-week old mice inhaled PM_2.5 that was concentrated from Chicago’s ambient air which contains several extensive sources of pollution including coal power plants, various industrial factories, and vehicle emissions.^{Reference Mutlu, Comba and Cho96} After being exposed to the concentrated PM_2.5 for 8 hours per day, 5 days per week for 3 weeks, the PM_2.5 exposed mice showed alterations in gut microbiome profile in the small intestine, colon, and feces as compared to filter air-exposed mice.^{Reference Mutlu, Comba and Cho96} Fujimura et al. collected house dust from households with (D) or without dogs (NP), and studied the gut microbiota of mice that were exposed to the dust by oral gavage.^{Reference Fujimura, Demoor and Rauch97} Interestingly, mice exposed to D dust exhibited a reduced pro-inflammatory response to cockroach allergen challenge as compared to NP dust-exposed mice. The D dust-exposed mice also showed a distinct gut microbiota profile compared with NP dust-exposed mice, and the bacterium, Lactobacillus Johnsonii (L. Johnsonii) was found to be enriched in the gut microbiome of D dust-exposed mice.^{Reference Fujimura, Demoor and Rauch97} In addition, L. Johnsonii-treated mice showed an overall reduction in the number of activated immune cells and airway Th2 cytokine expression.^{Reference Fujimura, Demoor and Rauch97}

Similarly, Kish et al. reported that mice gavaged with PM_2.5 and PM₁₀ had an altered gut microbiome and enhanced pro-inflammatory cytokine secretion in the small intestine.^{Reference Kish, Hotte and Kaplan98} Moreover, the mice exhibited increased intestinal permeability and altered concentrations of microbiota-derived metabolites and short-chain fatty acids.^{Reference Kish, Hotte and Kaplan98} In another study, 4-week-old mice that were subjected to 46 weeks of chronic PM exposure via versatile aerosol concentration enrichment system were shown to have a reduction in glucose and insulin tolerance, and this was accompanied by a significant reduction in richness of gut bacteria in mice.^{Reference Wang, Zhou and Chen99} Further analysis revealed significant correlations between PM exposure-induced gut microbiota alterations and abnormalities in glucose metabolism.^{Reference Wang, Zhou and Chen99} As compared to assessing associations between dust inhalation and gut microbiome in human studies,^{Reference Liu, Chen and Xu89,Reference Alderete, Jones and Chen90} oral gavage of dust in animals may allow us to study the direct effects of dust on the gut microbiome.^{Reference Fujimura, Demoor and Rauch97,Reference Kish, Hotte and Kaplan98} Collectively, the animal studies demonstrate that dust can directly alter gut microbiome and a dust-induced alteration in gut microbiota may partially explain the effect of dust on inflammation, gut permeability, and metabolism. The animal studies that examined the effect of dust exposure on microbiome and subsequent outcomes are summarized in Table 2.

Table 2.

Summary and comparison of animal studies involving air pollutants and subsequent outcomes

PM, particulate matter; BALF, bronchoalveolar lavage fluid; BMF, biomass fuel; MVE, motor vehicle exhaust; IL, interleukin; Ig, immunoglobin; TNF, tumor necrosis factor; CAP, concentrated ambient PM_2.5.

Mechanistic links between dust, human microbiome, and diseases

The human microbiome is known to contribute to an array of metabolic and immune processes through host–microbial exchange of metabolites, and to aid the maintenance of gut membrane integrity.^{Reference Postler and Ghosh100} Similarly, dust in the form of air pollutant or PM also affects immune responses,^{Reference Castaneda, Vogel, Bein, Hughes, Smiley-Jewell and Pinkerton101,Reference Miller and Peden102} systemic inflammation,^{Reference Pope, Bhatnagar, McCracken, Abplanalp, Conklin and O’Toole103,Reference Li, Dorans and Wilker104} gut permeability, and host metabolism.^{Reference Salim, Kaplan and Madsen105,Reference Mutlu, Engen and Soberanes106} Moreover, previous studies showed that dust is associated with a variety of human health disorders,^{Reference Shan, Wu, Fan, Haahtela and Zhang31} with the association perhaps mediated by modification of human microbiome.^{Reference Valles and Francino107} Taken together, dust may negatively impact health through alterations in the composition and functions (in terms of immune response, gut permeability, and metabolism) of human microbiome that will eventually contribute to the pathogenesis of NCDs (Fig. 1).

Fig. 1.

Mechanistic links between dust exposure and pathogenesis of non-communicable diseases.