“…This hypothesis proposed that a failure of immunoregulation and associated health problems (e.g., mental health conditions) in modern Western environments ( 83 ), indicated by a balanced expansion of effector T-cell populations and regulatory T cells (Treg), is due to reduced exposures to microorganisms with which humans coevolved, including: (i) pathogens associated with the “old infections” that were present throughout life in evolving human hunter-gatherer populations ( 114 ); (ii) the commensal microbiota, which have been altered by the modern Western lifestyle, including a diet that is frequently low in microbiota-accessible carbohydrates ( 115 – 117 ); and (iii) organisms from the natural environment with which humans were in daily contact with (and, consequently, had to be tolerated by the immune system) ( 83 ). More recently, the observation that two major socioecological trends (i.e., the loss of biodiversity, and increasing incidence of inflammatory diseases) are interdependent led to the biodiversity hypothesis ( 67 , 99 , 100 ). This states that people’s reduced contact with nature and environmental biodiversity has altered the human commensal microbiota’s capacity to induce immunoregulation and to prevent inappropriate inflammation as well as associated negative health outcomes ( 7 , 89 , 118 ).…”