Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair Respiratory tract infections are the most common infectious diseases, leading to global morbidity and mortality. Recent research has highlighted the role of lung microbiota in pulmonary diseases, although the mechanisms by which it affects the intestinal environment remain unclear. Gut microbial dysbiosis is associated with lung disease etiology or progression. This review discusses lung microbiome changes during respiratory infections, including reduced diversity and increased microbial burden, and their downstream effects on host-pathogen interactions, inflammation, and cytokine production. It focuses on the gut-lung bidirectional communication in shaping inflammation and immunity, reviewing both animal and human studies. The review also discusses novel microbial-based therapies, such as probiotics and bacteriophages, aimed at restoring microbial balance. Finally, it outlines key questions for future research with potential translational relevance for respiratory infection prevention and control. The lung microbiome is a transient bacterial community continuously inhaled and eliminated. It plays a critical role in lung homeostasis by inducing protective immune responses and inhibiting pathogens. Dysbiosis in the lung is associated with adverse biological events and respiratory disease progression. The lung microbiome is influenced by ecological factors, host interactions, and inflammatory responses. During disease, microbial communities in the lower airways resemble the oral microbiota. Studies show that respiratory infections are associated with increased microbial burden and reduced diversity, along with increased inflammation and tissue injury. Respiratory infections, such as pneumonia and viral infections, are influenced by the lung microbiome. The microbiome of the upper and lower respiratory tracts differs, with the lower tract having a lower microbial load. The lung microbiome is dynamic and distinct from high-biomass mucosae. During infections, the microbiome changes, affecting immune responses and disease outcomes. The gut-lung axis is crucial in shaping immune responses, with microbial exchange, metabolites, and immune cell trafficking playing a role in disease progression. The gut microbiota influences respiratory infections through immune modulation and microbial interactions. Dysbiosis in the gut is associated with increased susceptibility to respiratory infections. In COVID-19 patients, gut dysbiosis is linked to disease severity and post-COVID-19 syndrome. The gut microbiome can also influence the expression of ACE2, a receptor for SARS-CoV-2, contributing to disease susceptibility. The gut microbiota plays a critical role in respiratory infection outcomes, with dysbiosis linked to increased susceptibility. Antibiotic use can disrupt the gut microbiome, increasing microbial dissemination and disease severity. The gut microbiota shapes systemic immunity, with immune cells and cytokines triggered by gut microbes influencing disease progression. The gut-lung axis is a key factor in respiratory infections, with microbial interactions and immune responses playing a crucial role in disease outcomes. Future research is needed to fully understand the mechanisms and potential therapeutic applications of the gut-lung axis in respiratory infections.Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair Respiratory tract infections are the most common infectious diseases, leading to global morbidity and mortality. Recent research has highlighted the role of lung microbiota in pulmonary diseases, although the mechanisms by which it affects the intestinal environment remain unclear. Gut microbial dysbiosis is associated with lung disease etiology or progression. This review discusses lung microbiome changes during respiratory infections, including reduced diversity and increased microbial burden, and their downstream effects on host-pathogen interactions, inflammation, and cytokine production. It focuses on the gut-lung bidirectional communication in shaping inflammation and immunity, reviewing both animal and human studies. The review also discusses novel microbial-based therapies, such as probiotics and bacteriophages, aimed at restoring microbial balance. Finally, it outlines key questions for future research with potential translational relevance for respiratory infection prevention and control. The lung microbiome is a transient bacterial community continuously inhaled and eliminated. It plays a critical role in lung homeostasis by inducing protective immune responses and inhibiting pathogens. Dysbiosis in the lung is associated with adverse biological events and respiratory disease progression. The lung microbiome is influenced by ecological factors, host interactions, and inflammatory responses. During disease, microbial communities in the lower airways resemble the oral microbiota. Studies show that respiratory infections are associated with increased microbial burden and reduced diversity, along with increased inflammation and tissue injury. Respiratory infections, such as pneumonia and viral infections, are influenced by the lung microbiome. The microbiome of the upper and lower respiratory tracts differs, with the lower tract having a lower microbial load. The lung microbiome is dynamic and distinct from high-biomass mucosae. During infections, the microbiome changes, affecting immune responses and disease outcomes. The gut-lung axis is crucial in shaping immune responses, with microbial exchange, metabolites, and immune cell trafficking playing a role in disease progression. The gut microbiota influences respiratory infections through immune modulation and microbial interactions. Dysbiosis in the gut is associated with increased susceptibility to respiratory infections. In COVID-19 patients, gut dysbiosis is linked to disease severity and post-COVID-19 syndrome. The gut microbiome can also influence the expression of ACE2, a receptor for SARS-CoV-2, contributing to disease susceptibility. The gut microbiota plays a critical role in respiratory infection outcomes, with dysbiosis linked to increased susceptibility. Antibiotic use can disrupt the gut microbiome, increasing microbial dissemination and disease severity. The gut microbiota shapes systemic immunity, with immune cells and cytokines triggered by gut microbes influencing disease progression. The gut-lung axis is a key factor in respiratory infections, with microbial interactions and immune responses playing a crucial role in disease outcomes. Future research is needed to fully understand the mechanisms and potential therapeutic applications of the gut-lung axis in respiratory infections.