Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.

Bypassing the Gut-Lung Axis via Microbial Metabolites: Implications for Chronic Respiratory Diseases.

The gut microbiome engages in constant interactions with the immune system, laying down the fundamentals of what we perceive as health or disease. The gut microbiota acts locally in the intestines and distally in other organs, such as the lungs. This influence (termed "the gut-lung axis") constitutes the basis for harnessing the microbiome to prevent or treat chronic respiratory diseases. Within this context, two approaches gained the most attention: the diet interventions (which shape the microbiome) and the probiotics (which exert beneficial effects directly on the host). Microbial products, which constitute a means of communication along the gut-lung axis, are only now emerging as a new class of potential therapeutics. Here, we provide a comprehensive overview of microbial products active in the airways, describe the immunological mechanisms they trigger, and discuss their clinical advantages and pitfalls.

Bile acids in immunity: Bidirectional mediators between the host and the microbiota.

Host-microbiota interactions are bidirectional. On one hand, ecological pressures exerted by the host shape the composition and function of the microbiota. On the other, resident microbes trigger multiple pathways that influence the immunity of the host. Bile acids participate in both parts of this interplay. As host-derived compounds, they display bacteriostatic properties and affect the survival and growth of the members of the microbial community. As microbiota-modified metabolites, they further influence the microbiota composition and, in parallel, modulate the immunity of the host. Here, we provide a comprehensive overview of the mechanisms behind this unique dialogue and discuss how we can harness bile acids to treat intestinal inflammation.