Lung-gut connection: mucosal immune cross-talk leading to disease in distant organs

Respiratory and gastrointestinal diseases are often manifested as overlapping conditions. The respiratory and gastrointestinal tracts have many similarities, which may account for some common pathological features observed in diseases affecting these two systems. Irritable bowel syndrome (IBS) and asthma, two common disorders of the gastrointestinal and respiratory tracts, respectively, are associated with increased mucosal immune activation. A bidirectional association between asthma and IBS has been reported by many authors, suggesting that these conditions may share a similar pathophysiology. However, this association is based on epidemiological data and clinical observations and there is a need for basic research to elucidate the associations and mechanisms involved. Of interest, several studies have shown cross-mucosal immune interaction between the airways and the and gut. Influenza lung infection has been shown to alter the gut microbiota and promote an increase in flu-specific T cells in the small intestine. Moreover, gastrointestinal infections caused by bacteria or viruses protect against counterpart pathogens causing respiratory infections. These data indicate that immune responses generated in the lung may have a profound effect in the gut and vice versa. In the present PhD project, our goal is to evaluate the cross-talk between an increased mucosal immune activation in the lung towards the gut (and from the gut towards the lung), and how this affects neuronal sensitization in distant organs. We hypothesize that immune responses against aeroallergens in the lung prime for similar responses in the intestinal mucosa, leading to visceral hypersensitivity. Similarly, immune responses originated in the gut affect lung mucosa leading to airway hyperresponsiveness. The results obtained during this project will provide novel insights on the biological mechanisms underlying the association between asthma and IBS, and other respiratory and gut disorders.