Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health

Abstract

Epidemiological studies suggest that living close to the natural environment is associated with long-term health benefits including reduced death rates, reduced cardiovascular disease, and reduced psychiatric problems. This is often attributed to psychological mechanisms, boosted by exercise, social interactions, and sunlight. Compared with urban environments, exposure to green spaces does indeed trigger rapid psychological, physiological, and endocrinological effects. However, there is little evidence that these rapid transient effects cause long-term health benefits or even that they are a specific property of natural environments. Meanwhile, the illnesses that are increasing in high-income countries are associated with failing immunoregulation and poorly regulated inflammatory responses, manifested as chronically raised C-reactive protein and proinflammatory cytokines. This failure of immunoregulation is partly attributable to a lack of exposure to organisms ("Old Friends") from mankind's evolutionary past that needed to be tolerated and therefore evolved roles in driving immunoregulatory mechanisms. Some Old Friends (such as helminths and infections picked up at birth that established carrier states) are almost eliminated from the urban environment. This increases our dependence on Old Friends derived from our mothers, other people, animals, and the environment. It is suggested that the requirement for microbial input from the environment to drive immunoregulation is a major component of the beneficial effect of green space, and a neglected ecosystem service that is essential for our well-being. This insight will allow green spaces to be designed to optimize health benefits and will provide impetus from health systems for the preservation of ecosystem biodiversity.

Fig. 1.

The immune system does not develop normally in the absence of microbial inputs. In addition to a repertoire of potential effector cells, the system also requires regulatory circuits that inhibit damaging responses to inappropriate targets (such as self, trivial antigens in air, and gut contents) and that terminate inflammatory responses that are no longer needed. The disease groups that occur when immunoregulation fails are indicated in parentheses.

Fig. 2.

A simple classification of organisms and parasites with which humans coevolved and that have been implicated by epidemiology or experimental models in the modulation of immunoregulation (although those listed as carrier states might be biomarkers of exchange of microbiota with other humans). The modern urban environment eliminates the first three categories, thus increasing our dependence on microbiota from other humans and from the natural environment.

Fig. 3.

Multiple ways in which the microbiota of the natural environment can modulate the immune system. This modulation may or may not involve colonization. There can be direct interaction with the immune system (pathway D) or indirect effects secondary to changes in the microbiota (pathways A, B, and C, fully explained in text).

Fig. 4.

Immunological and psychological explanations for the health benefits derived from contact with the natural environment. (NO, nitric oxide). There are many studies of exposures during the perinatal period that point to the immunological mechanisms, whereas most studies in adult life have been orientated toward psychological explanations, and have not included investigation of the immunoregulatory aspects.