Download PDF Microbiomes of the Built Environment September 15, 2022 Volume 52 Issue 3 The covid-19 pandemic suddenly directed awareness to potential health impacts of the built environment of everyday living – schools, dwellings, offices, public buildings, and other spaces. This issue explores the “microbiome” of the built environment in the postpandemic reality in terms of ventilation performance, filtration, understanding and quantification of transmission risk, protection of “benign” microbes, and the important role of equity, among others. Embracing Healthy Microbiomes, Including Access to Nature and Pets Monday, September 19, 2022 Author: Megan S. Thoemmes, Sarah M. Allard, and Jack A. Gilbert Beneficial microbial and macrobial exposures can increase immune health and reduce the spread of disease. “…to maintain the air within the room as fresh as the air without.…” – Florence Nightingale (1859) Microbial interactions that occur in built spaces are strong determinants of human health. These interactions underlie the need to establish diverse, long-term exposures that regulate immune development and to limit short-term exposures to specific taxa that can lead to infection, death, or detrimental neurological effects. Yet, despite long-standing recognition of the importance of human-microbe interactions indoors, the microbiology of the built environment (BE) has never been so much at the nexus of attention and study as it has been since the start of the covid-19 pandemic. SARS-CoV-2, the virus that causes covid-19, has led to unprecedented shifts in sociocultural behaviors and keen interest in the potential for microbial transmission in homes, offices, hospitals, schools, and other public places. However, the full biological and physicochemical context of the built environment must also be considered, as it can influence the distribution of a pathogen, including species abundances and functional potential of microbes that can survive in a harsh, highly selective environment. Here, we discuss how the indoor microbiome is shaped by BE use and design, how this affects pathogen transmission, how the covid-19 pandemic has altered behavior and building management practices, and finally, how built environments can be manipulated to create healthier spaces. Microbiology of the Built Environment Many animals construct their own dwellings. Ants, termites, bees, and wasps are obvious examples, and many birds, mammals, reptiles, and amphibians also construct their own spaces to create a protective environment. In some cases, animals have been shown to manipulate their BE microbiome to promote positive microbial interactions. For example, the beewolf digger wasp actively cultures bacteria from the genus Streptomyces to include in the construction of its larval housing, the cocoon (Kaltenpoth et al. 2005; Kroiss et al. 2010). These bacteria provide biocontrol against potentially harmful fungal pathogens by significantly increasing the probability of larval survival through the production of antifungal compounds, including antibiotics like -streptochlorin and piericidin derivatives (Kroiss et al. 2010). Human history similarly offers examples of active engagement in biocontrol in built structures. Attempts to control BE microbiology have largely stemmed from a fear of disease, and efforts to characterize the origin and long-term viability of BE-associated micro-organisms were based on the recognition that their eradication would be beneficial (Lidwell and Lowbury 1950; Wright et al. 1944). For thousands of years, it has been known that indoor dampness affects human health, yet it was not until the 19th century that a link was made to micro-organisms (Carnelley et al. 1887), and it is only in the past 20 years that researchers have attempted to understand the microbiome of dwellings with respect to their ecology (Gilbert and Stephens 2018). Modern molecular approaches have made it possible to rapidly and cost-effectively characterize the microbial communities of homes, workspaces, and hospitals; identify the factors that impact their temporal dynamics; and distinguish the building and lifestyle factors that determine their survivability and activity (Gilbert and Stephens 2018; Kelley and Gilbert 2013; Stephens et al. 2019). With this new knowledge, the scientific community is exploring how best to manage BE microbiology to enhance health-promoting interactions. Efforts include the use of biocontrol with living microorganisms (Caselli et al. 2016; González et al. 2020; Vandini et al. 2014) and exploration of how building use could influence potential health outcomes (Kembel et al. 2012). Contributors to the Built Environment Microbiome Humans The human microbiome is not limited to what is found on and in the human body. Humans shed nearly a billion bacteria a day and are frequently colonized by microorganisms, resulting in continual exchange with surrounding people and places (Stephens et al. 2019). Homes and other buildings host sloughed-off skin and microbes, and they are the places where people are most commonly exposed to other species (Gilbert and Stephens 2018). Buildings are often designed to limit exposure to the outdoor environment, decreasing the rateof colonization by outdoor species. Not only do people spend most of their time indoors (Klepeis et al. 2001), but buildings are often intentionally designed to limit exposure to the outdoor environment, thereby decreasing the rate of colonization by outdoor species (Lax et al. 2014). Thus, the built environment can be considered an extension of an individual’s microbial self, as it is inoculated so readily by microbes from the body that the microbial signature of a new occupant in a room can be detected within 24 hours (Lax et al. 2014, 2017). Pets and Pests Pets and/or pests can also significantly contribute to the indoor microbiome, with beneficial or negative health outcomes (Richardson et al. 2019). Animals such as dogs and some livestock increase microbial diversity and promote species interactions that provide a protective effect against the development of allergic diseases (Fujimura et al. 2014; Lynch et al. 2014; Stein et al. 2016). Alternatively, cats, rodents, and certain insects (e.g., bed bugs and dust mites) can introduce pathogens and allergens and alter the house microbiome and metabolome (box 1) in ways that could be detrimental for occupant health (Kakumanu et al. 2020; Martinez et al. 2018; Salo et al. 2018). Pathogens Further, the composition of microbes found in the BE is modulated not only by occupants’ presence but also by their disease state (Cantú et al. 2022; Marotz et al. 2021). Recent studies have demonstrated that, although it is primarily transmitted through the air, SARS-CoV-2 is detectable on surfaces in rooms with covid-positive patients and that this distribution is strongly correlated with the proportion of specific bacterial taxa (Ben-Shmuel et al. 2020; Marotz et al. 2021; Zhou et al. 2021). We hypothesize that this could be due to a physical interaction between the virus and the bacterium, which enhances viral stability and survivability outside the body (Neu and Mainou 2020). Although their association has not been fully established, Rothia bacteria have been found to correlate with the presence of SARS-CoV-2, both in the human body and on hospital and residential surfaces (Ben-Shmuel et al. 2020; Marotz et al. 2021). These studies provide only a glimpse into the complexity of interactions between humans, their microbes, and the microbes of the spaces they occupy, highlighting the importance of considering both the broader ecology of BE-associated communities and fine-scale species interactions. Association between Building Design and Pathogen Dynamics Archeological studies have shown how the design and use of built environments have influenced the frequency of humans’ exposure to disease-causing organisms (Fink 1985). For example, it was proposed that interior rooms in ancestral pueblo homes (New Mexico; 900–1300 AD) had a higher abundance of Mycobacterium tuberculosis, as compared to exterior rooms, because of reduced exposure to direct sunlight and low ventilation rates (Frobisher and Fuerst 1983). Contemporary BEs have become even more sealed and modified, now strikingly distinct from the natural world (e.g., many surface habitats are often severely limited in the availability of water and nutrients), and these conditions have imposed selective pressures on the microbes that can colonize and persist inside. This environmental stress triggers horizontal gene transfer events that facilitate the acquisition of new genes and hence phenotypes (Lax et al. 2017, 2019). In addition, microbial adaptations needed for survival can lead to an increase in antimicrobial resistance and/or virulence over time, as has been shown both in hospitals and on spacecraft (Lax et al. 2017; Urbaniak et al. 2019). This genetic selection for pathogenic traits is compounded by the loss of many potentially beneficial organisms through attempts to chemically or mechanically remove microbial life in human-occupied spaces (Gilbert and Stephens 2018). People now come in contact with a smaller subset of diverse organisms that are important not only for immune development (Stein et al. 2016) but also for the reduction of pathogen abundance indoors (Kembel et al. 2012). The author of the first book on nursing, Florence Nightingale (1859), championed the value of opening windows to increase patients’ rate of healing and decrease the rate of death. Opening windows is likely to shape the indoor environment in a variety of ways that can benefit patient health (e.g., by increasing oxygen levels). However, here we focus specifically on the effect on the microbiome. Since Nightingale’s time, it has been shown that hospital rooms ventilated with open windows have greater microbial taxonomic diversity and a reduction in the proportion of potential pathogens (Kembel et al. 2012), highlighting the benefit of increased ventilation indoors in mediating the spread of disease. This small action can not only greatly reduce airborne pathogens (which is particularly important when considering viruses that spread in the same ways as SARS-CoV-2) but also create a more complex, competitive environment for pathogens that are typically spread through the touching of surfaces (Stephens et al. 2019). Influence of the Covid-19 Pandemic on Ventilation and Cleaning Practices Since the onset of the covid-19 pandemic in March 2020, there has been a shift in public awareness of and approaches to ventilation and cleaning, in both private and public settings; see, for example, the Department of Education guidelines for improving ventilation in schools, colleges, and universities and the Centers for Disease Control and Prevention (CDC) guidance for improving ventilation in homes. With respect to cleaning, the CDC reported a 20 percent increase in the number of calls to Poison Control about exposure to cleaners and disinfectants from January to March 2020, compared to the same period in the previous 2 years (Chang et al. 2020), indicating an increase both in the use of such products (e.g., bleach) and in unsafe practices with their use (e.g., soaking fresh produce). As the pandemic continued, scientific studies and outbreak tracing provided clarity on the most prevalent transmission routes of the SARS-CoV-2 virus, showing that person-to-person contact and air are the primary routes of transmission and that surface-based transmission is less likely to result in infection (Prather et al. 2020). This revelation has led to unprecedented public interest in ventilation efficiency (e.g., optimization of air changes per hour, ACH), air filtration practices, and changes to building infrastructure. For example, the CDC recommends improved ventilation as a core mitigation strategy in a layered approach to covid-19 safety in public buildings, including schools. As one example, the University of California San Diego shifted to outdoor classes and upgraded ventilation and air filtration for indoor spaces (see UCSD Return to Learn). Approaches implemented to decrease SARS-CoV-2 transmission had a preventive impact on the spread of other diseases. These changes in building use, management, and cleaning practices could have long-term impacts on BE microbiomes. Air filtration and ventilation improvements will further influence microbial community composition/complexity and rates of disease transmission. During the first 2 years of the pandemic, a concurrent decrease in seasonal flu cases (Hayashi and Konishi 2021; Servick 2021) demonstrated that approaches implemented to decrease SARS-CoV-2 transmission had a preventive impact on the spread of other diseases (Zhang et al. 2021). On the other hand, there is growing concern over the probable increase in the emergence of antibiotic-resistant microorganisms and healthcare-associated infections (HAIs) since the onset of the pandemic, potentially due in part to altered cleaning regimes (Lobie et al. 2021; Mahoney et al. 2021; Seethalakshmi et al. 2022). HAIs are a leading cause of death worldwide (Haque et al. 2018), so the need to develop optimized disease management strategies indoors is of exceptional importance. Targeted Approaches to Support Healthy BE Microbiomes To maximize human health in the 21st century, scientists and architects must consider novel ways to design, construct, and manage buildings and cities in a manner that will promote healthy microbial interactions. Improved indoor air quality is a well-established strategy to benefit human health, and can be augmented by innovating strategies that further increase exposure to beneficial microbes, by, for example, advising increased interaction with certain types of pets (especially for young, nonatopic children) and time spent outdoors. Because there are many scenarios in which such measures are not possible, we envisage a future where microbial biocontrol can be engineered into building materials (i.e., living buildings) (Beckett 2021; González et al. 2020; Ramirez-Figueroa and Beckett 2020) to provide surfaces that both actively reduce the emergence and persistence of dangerous pathogens and create immune-activating exposure to decrease the incidence of chronic immune disease (Gilbert et al. 2018; Stein et al. 2016). This would also lessen the likelihood of exposure to allergens, such as animal dander, that could exacerbate allergic symptoms. A future that involves biologically active building materials and breathing urban spaces could have profound positive outcomes for health and quality of life. There is still much work to be done to determine which beneficial species are safe for all individuals, particularly those who are immunocompromised, and so we argue that research supporting this vision should be prioritized. Conclusion Despite a clear understanding of the potential risk of detrimental microbial exposures in indoor and urban settings, researchers are only just beginning to fully comprehend the implications of actively altering these interactions. The SARS-CoV-2 pandemic provided an ideal opportunity to accelerate research on ways to further reduce pathogenic exposures in homes, offices, and schools. However, it also reignited the question, How clean is too clean? The built environment has been compared to a biological wasteland (Gibbons 2016), but the future of this field points to a reversal of this paradigm, toward repopulating indoor spaces and urban places with beneficial microbial and macrobial experiences. Living buildings might provide targeted beneficial exposures to improve human health and vitality. References Adams RI, Lymperopoulou DS, Misztal PK, Pessotti RDC, Behie SW, Tian Y, Goldstein AH, Lindow SE, Nazaroff WW, Lindow SE, and 2 others. 2017. Microbes and associated soluble and volatile chemicals on periodically wet household surfaces. Microbiome 5(1):128. Beckett R. 2021. Probiotic design. Architecture 26(1):6–31. Ben-Shmuel A, Brosh-Nissimov T, Glinert I, Bar-David E, Sittner A, Poni R, Cohen R, Achdout H, Tamir H, Yahalom-Ronen Y, and 11 others. 2020. Detection and infectivity potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in isolation units and quarantine facilities. Clinical Microbiology & Infection 26(12):1658–62. Cantú VJ, Salido RA, Huang S, Rahman G, Tsai R, Valentine H, Magallanes CG, Aigner S, Baer NA, Barber T, and 30 others. 2022. SARS-CoV-2 distribution in residential housing suggests contact deposition and correlates with Rothia sp. mSystems 7(3):e01411-21. Carnelley T, Haldane JS, Anderson AM. 1887. The carbonic acid, organic matter, and micro-organisms air, more especially of dwellings and schools. Philosophical Transactions of the Royal Society B: Biological Sciences 178:61–111. Caselli E, D’Accolti M, Vandini A, Lanzoni L, Camerada MT, Coccagna M, Branchini A, Antonioli P, Balboni PG, Di Luca D, Mazzacane S. 2016. Impact of a probiotic-based cleaning intervention on the microbiota ecosystem of the hospital surfaces: Focus on the resistome remodulation. PLoS One 11(2):e0148857. Chang A, Schnall AH, Law R, Bronstein AC, Marraffa JM, Spiller HA, Hays HL, Funk AR, Mercurio-Zappala M, Calello DP, and 4 others. 2020. Cleaning and disinfectant chemical exposures and temporal associations with COVID-19 — National poison data system, United States, January 1, 2020–March 31, 2020. Morbidity & Mortality Weekly Report 69(16):496–98. Evans GW. 2003. The built environment and mental health. Urban Health 80(4):536–55. Ezeonu IM, Price DL, Simmons RB, Crow SA, Ahearn DG. 1994. Fungal production of volatiles during growth on fiberglass. Applied & Environmental Microbiology 60(11):4172–73. Fink TM. 1985. Tuberculosis and anemia in a Pueblo II-III (ca. AD 900–1300) Anasazi child from New Mexico. In: Health and Disease in the Prehistoric Southwest, ed. Merbs CF, Miller RJ, Dyer Alcauskas ES; pp. 359–79. Tempe: -Arizona State University. Frobisher M, Fuerst R. 1983. Microbiology in Health and Disease. Philadelphia: WB Saunders. Fujimura KE, Demoor T, Rauch M, Faruqi AA, Jang S, Johnson CC, Boushey HA, Zoratti E, Ownby D, Lukacs NW, Lynch SV. 2014. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proceedings of the National Academy of Sciences 111(2):805–10. Gibbons SM. 2016. The built environment is a microbial wasteland. mSystems 1(2):e00033-16. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. 2018. Current understanding of the human microbiome. Nature Medicine 24(4):392–400. Gilbert JA, Stephens B. 2018. Microbiology of the built environment. Nature Reviews Microbiology 16(11):661–70. González LM, Mukhitov N, Voigt CA. 2020. Resilient living materials built by printing bacterial spores. Nature Chemical Biology 16(2):126–33. Haque M, Sartelli M, McKimm J, Bakar MA. 2018. Health care-associated infections – an overview. Infection & Drug Resistance 11:2321–33. Hayashi T, Konishi I. 2021. Significant decrease in seasonal influenza in the COVID-19 era: Impact of global movement restrictions? Clinical Medicine Research 13(3):191–94. Kakumanu ML, DeVries ZC, Barbarin AM, Santangelo RG, Schal C. 2020. Bed bugs shape the indoor microbial community composition of infested homes. Science of the Total Environment 743:140704. Kaltenpoth M, Göttler W, Herzner G, Strohm E. 2005. Symbiotic bacteria protect wasp larvae from fungal infestation. Current Biology 15(5):475–79. Kelley ST, Gilbert JA. 2013. Studying the microbiology of the indoor environment. Genome Biology 14(2):202. Kembel SW, Jones E, Kline J, Northcutt D, Stenson J, Womack AM, Bohannan BJM, Brown GZ, Green JL. 2012. Architectural design influences the diversity and structure of the built environment microbiome. ISME Journal 6(8):1469–79. Kirjavainen PV, Täubel M, Karvonen AM, Sulyok M, Tiittanen P, Krska R, Hyvärinen A, Pekkanen J. 2016. Microbial secondary metabolites in homes in association with moisture damage and asthma. Indoor Air 26(3):448–56. Klepeis NE, Nelson WC, Ott WR, Robinson JP, Tsang AM, Switzer P, Behar JV, Hern SC, Engelmann WH. 2001. The National Human Activity Pattern Survey (NHAPS): A resource for assessing exposure to environmental pollutants. Exposure Science & Environmental Epidemiology 11(3):231–52. Kroiss J, Kaltenpoth M, Schneider B, Schwinger MG, Hertweck C, Maddula RK, Strohm R, Svatoš A. 2010. Symbiotic streptomycetes provide antibiotic combination prophylaxis for wasp offspring. Nature Chemical Biology 6(4):261–63. Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM, Scott NM, Gibbons SM, Larsen P, Shogan BD, Weiss S, and 10 others. 2014. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345(6200):1048–52. Lax S, Sangwan N, Smith D, Larsen P, Handley KM, -Richardson M, Guyton K, Krezalek M, Shogan BD, Defazio J, and 10 others. 2017. Bacterial colonization and succession in a newly opened hospital. Science Translational Medicine 9(391):eaah6500. Lax S, Cardona C, Zhao D, Winton VJ, Goodney G, Gao P, Gottel N, Hartmann EM, Henry C, Thomas PM, and 3 others. 2019. Microbial and metabolic succession on common building materials under high humidity conditions. Nature Communications 10(1):1767. Lidwell OM, Lowbury EJ. 1950. The survival of bacteria in dust. I. The distribution of bacteria in floor dust. Hygiene 48(1):6–20. Lobie TA, Roba AA, Booth JA, Kristiansen KI, Aseffa A, Skarstad K, Bjørås M. 2021. Antimicrobial resistance: A challenge awaiting the post-COVID-19 era. International Journal of Infectious Diseases 111:322–25. Lynch SV, Wood RA, Boushey H, Bacharier LB, Bloomberg GR, Kattan M, O’Connor GT, Sandel MT, Calatroni A, Matsui E, and 11 others. 2014. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. Allergy & Clinical Immunology 134(3):593-601. Mahoney AR, Safaee MM, Wuest WM, Furst AL. 2021. The silent pandemic: Emergent antibiotic resistances following the global response to SARS-CoV-2. iScience 24(4):102304. Marotz C, Belda-Ferre P, Ali F, Das P, Huang S, Cantrell K, Jiang L, Martino C, Diner RE, Rahman G, and 25 others. 2021. SARS-CoV-2 detection status associates with bacterial community composition in patients and the hospital environment. Microbiome 9(1):132. Martinez VO, de Mendonça Lima FW, de Carvalho CF, Menezes-Filho JA. 2018. Toxoplasma gondii infection and behavioral outcomes in humans: A systematic review. Parasitology Research 117(10):3059–65. Neu U, Mainou BA. 2020. Virus interactions with -bacteria: Partners in the infectious dance. PLoS Pathogens 16(2):e1008234. Nightingale F. 1859. Notes on Nursing: What It Is, and What It Is Not. London: Harrison & Sons. Prather KA, Wang CC, Schooley RT. 2020. Reducing transmission of SARS-CoV-2. Science 368(6498):1422–24. Ramirez-Figueroa C, Beckett R. 2020. Living with buildings, living with microbes: Probiosis and architecture. Architectural Research Quarterly 24(2):155–68. Richardson M, Gottel N, Gilbert JA, Gordon J, Gandhi P, Reboulet R, Hampton-Marcell JT. 2019. Concurrent measurement of microbiome and allergens in the air of bedrooms of allergy disease patients in the Chicago area. Microbiome 7(1):82. Salo PM, Cohn RD, Zeldin DC. 2018. Bedroom allergen exposure beyond house dust mites. Current Allergy and Asthma Reports 18(10):52. Schleibinger H, Laussmann D, Bornehag CG, Eis D, Rueden H. 2008. Microbial volatile organic compounds in the air of moldy and mold-free indoor environments. Indoor Air 18(2):113–24. Seethalakshmi PS, Charity OJ, Giakoumis T, Kiran GS, Sriskandan S, Voulvoulis N, Selvin J. 2022. Delineating the impact of COVID-19 on antimicrobial resistance: An Indian perspective. Science of the Total Environment 818:151702. Servick K. 2021. COVID-19 measures also suppress flu—for now. Science 371(6526):224. Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, -Murray SE, Ledford JG, dos Santos MM, Anderson RL, Metwali N, and 10 others. 2016. Innate immunity and asthma risk in Amish and Hutterite farm children. New England Journal of Medicine 375(5):411–21. Stephens B, Azimi P, Thoemmes MS, Heidarinejad M, Allen JG, Gilbert JA. 2019. Microbial exchange via fomites and implications for human health. Current Pollution Reports 5:198–213. Urbaniak C, van Dam P, Zaborin A, Zaborina O, Gilbert JA, Torok T, Wang CCC, Venkateswaran K. 2019. Two novel Fusarium oxysporum isolates cultured from the International Space Station are potentially virulent. mSystems 4(2):e00345-18. Vandini A, Temmerman R, Frabetti A, Caselli E, Antonioli P, Balboni PG, Platano D, Branchini A, Mazzacane S. 2014. Hard surface biocontrol in hospitals using microbial-based cleaning products. PLoS One 9(9):e108598. Wright J, Cruickshank R, Gunn W. 1944. Control of dust-borne streptococcal infection in measles wards. British Medical Journal 1(4348):611–14. Zhang N, Jia W, Lei H, Wang P, Zhao P, Guo Y, Dung CH, Bu Z, Xue P, Xie J, and 3 others. 2021. Effects of human behavior changes during the coronavirus disease 2019 (COVID-19) pandemic on influenza spread in Hong Kong. Clinical Infectious Diseases 73(5):e1142–50. Zhou J, Otter JA, Price JR, Cimpeanu C, Garcia DM, Kinross J, Boshier PR, Mason S, Bolt F, Holmes AH, Barclay WS. 2021. Investigating severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) surface and air contamination in an acute healthcare setting during the peak of the coronavirus disease 2019 (COVID-19) pandemic in London. Clinical Infectious Diseases 73(7):e1870–77.  https://www.ed.gov/improving-ventilation-schools-colleges- and-universities-prevent-covid-19  https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting- sick/improving-ventilation-home.html  https://www.cdc.gov/coronavirus/2019-ncov/community/- ventila tion.html About the Author:Megan Thoemmes is a postdoctoral scholar, Sarah Allard an assistant project scientist, and Jack Gilbert a professor, all in the Department of Pediatrics and Scripps Institution of Oceanography, University of California San Diego School of Medicine.