Figure 7.

Hypothetical model for microbiome-host interactions in the gut ecosystem of AD during early life. In the non-AD group, the gut microbiome develops during early childhood by colonizing microbes at the appropriate time. Early colonizing facultative anaerobes gradually shift to strict anaerobes by utilizing oxygen to create an anaerobic gut environment. Adequate maturation of the gut microbiome regulates SCFAs production and immune development throughout early childhood. Butyrate produced by strict anaerobes activates PPAR-γ, mitochondrial respiration, and increases oxygen consumption through oxidative phosphorylation. Thus, it maintains an anaerobic environment by reducing oxygen emanation from the mucosa. Moreover, the butyrate induces T_reg cells, which control Th₂ inflammation. In the AD group, this cyclic interaction is imbalanced, exacerbating the homeostasis of the gut ecosystem. An abnormal oxygen environment in the gut maintains facultative anaerobes during childhood; it limits B. fragilis colonization throughout the lifespan. Disordered gut microbiome development is related to decreased butyrate production and abnormal immune responses. PPAR-γ and T_reg cells cannot be activated with a decrease in butyrate. The epithelial proliferation and mitochondrial respiration decrease, and the emanating oxygen and lactate from mucosa increase by anaerobic glycolysis of the host cell. Facultative anaerobes use lactate produced by the host cell. Abnormal T_reg and epithelial cell proliferation and the increased numbers of facultative anaerobes induce abnormal immune responses.