Early-Life Formation of the Microbial and Immunological Environment of the Human Airways

Abstract

Crosstalk between immune cells and the microbiota in mucosal tissues can set an individual on a trajectory toward health or disease. Little is known about these early-life events in the human respiratory tract. We examined bacterial colonization and immune system maturation in the lower airways over the first year of life. The lower respiratory tract microbiota forms within the first 2 postnatal months. Within the first weeks, three microbial profiles are evident, broadly distinguished as dysbiotic or diverse, and representing different microbial virulence potentials, including proteolysis of immunoglobulin A (IgA) that is critical for mucosal defense. Delivery mode determines microbiota constituents in preterm, but not term, births. Gestational age is a key determinant of immune maturation, with airway cells progressively increasing expression of proallergic cytokine interleukin-33 and genes linked with IgA. These data reveal microbial and immunological development in human airways, and may inform early-life interventions to prevent respiratory diseases.

Legionella pneumophilainfection and antibiotic treatment engenders a highly disturbed pulmonary microbiome with decreased microbial diversity

“…Similar to our results where an association in a co-occurrence network of Fusobacterium and Prevotella was observed such an interaction was also described for the lung microbiome of healthy individuals [4]. Cluster 6 included the genera Neisseria and Streptococcus , both have recently been proposed as keystone species for the community structure of healthy neonatal airways [50].…”

The vagino-cervical microbiome as a woman’s life history

“…7_1_47FAA (Figure 6D, Table S3). We observed a lower relative abundance of Ureaplasma parvum in individuals who delivered by cesarean section (Figure 6E, Table S3), a bacterium commonly isolated from pregnant women (Anderson et al, 2013) and recently reported in the lower respiratory tract of preterm infants (Pattaroni et al, 2018) and in preterm placenta (de Goffau et al, 2019). Compared with vaginal deliveries, the plasma concentrations of testosterone, androstenedione, methionine, threonine and tryptophan were significantly lower in women who experienced caesarean section (Figure 6D, 6E).…”

Microbes, metabolites, and the gut–lung axis

“…48,52,53 Studies by our group have indicated that the airway microbiome forms rapidly post-birth, reaching its mature diversity within 2-3 post-natal weeks in mice 54 and 2-3 post-natal months in humans. 55 In mice, formation of the airway microbiome coincides with immune maturation steps that underlie the development of tolerance to inhaled allergens. 54 In humans, it is not feasible to track the lower airway microbiome longitudinally, however, the constituents of the microbiome associated with distinct steps of immune maturation indicative of ongoing crosstalk between the airway resident microbes and immune cells.…”