Do airborne biogenic chemicals interact with the PI3K/Akt/mTOR cell signalling pathway to benefit human health and wellbeing in rural and coastal environments?

Abstract

Living and taking recreation in rural and coastal environments promote health and wellbeing, although the causal factors involved are unclear. It has been proposed that such environments provide a counter to the stresses of everyday living, leading to enhanced mental and physical health. Living in natural environments will result in airborne exposure to a wide range of biogenic chemicals through inhalation and ingestion of airborne microbiota and particles. The "biogenics" hypothesis formulated here is that regular exposure to low concentrations of mixtures of natural compounds and toxins in natural environments confers pleiotropic health benefits by inhibiting the activities of interconnected cell signalling systems, particularly PI3K/Akt/mTORC1. When overactive, Akt and mTOR (mTORC1) can lead to many pathological processes including cancers, diabetes, inflammation, immunosuppression, and neurodegenerative diseases. There is a substantial body of evidence that many natural products (i.e., from bacteria, algae, fungi and higher plants) inhibit the activities of these protein kinases. Other mTOR-related interconnected metabolic control "switches" (e.g., PTEN & NF-κB), autophagy and other cytoprotective processes are also affected by natural products. The "biogenics" hypothesis formulated here is that regular intermittent exposure to a mixture of airborne biogenic compounds in natural environments confers pleiotropic health benefits by inhibiting activities of the highly interconnected PI3K/Akt/mTORC1 system. It is proposed that future experimental exposures to biogenic aerosols in animal models coupled with epidemiology, should target the activities of the various kinases in the PI3K/Akt/mTORC1 systems and related physiological processes for selected urban, rural and coastal populations in order to test this hypothesis.

Penicillium expansum strain isolated from indoor building material was able to grow on gypsum board and emitted guttation droplets containing chaetoglobosins and communesins A, B and D

“…The weakened immune tolerance reported from urban environments caused by depleted and poor outdoor microbial diversity (Moore 2015;Schuijs et al 2015;von Hertzen et al 2015;Haahtela et al 2015;Adams et al 2016;Mhuireach et al 2016;Stein et al 2016;Li et al 2018) may be attenuated by exposure to indoor microbes producing toxins inducing loss of tolerance (TILT ;Miller 1997;Genius 2010). We were tempted to speculate that the absence of a diverse protective microbiome in combination with exposure to microbial TILT may be a potential factor to contribute to the diverse indoor air-related Table 4 The airborne transit of mycotoxins contained in exudate droplets of Penicillium expansum RcP61 from the mycelial mass towards a cool surface in the experimental set-up shown in Fig.…”

A biodiversity hypothesis

“…The concept of biodiversity can be extended from living species even to biogenic chemicals. In natural environment, we inhale and ingest a wide range of airborne biogenic chemicals in addition to microbiota and particles . This cocktail is very different in urban environments, but very little is known of its composition or immunogenicity.…”

The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health

“…In addition to commensal and mutualistic microorganisms and the “Old Infections”, environmental microorganisms also induce immunoregulation following ingestion [106] or inhalation [107;108]. These organisms have been referred to as “pseudocommensals” because they would have been present in large numbers throughout mammalian evolution, even if they do not colonize the gut [20;109].…”