Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

Abstract

Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.

Unraveling the gut-Lung axis: Exploring complex mechanisms in disease interplay

“…Based on multiple signals derived from the microbiota, gut and lung may have bidirectional interactions. However, the outcomes are still incompletely understood [ 69 ]. Exploring these possibilities is an exciting and vital task for future research.…”

Gut‐lung axis and asthma: A historical review on mechanism and future perspective

“…Accordingly, research on helminth therapy provides another clue to the benefits of gut microbiota balance on the respiratory system, and it is also expected to become another clue for the prevention and treatment of asthma. Researchers have discovered that helminths affect the composition of gut microbiota and indirectly affect the lung immune response and prevent asthma attacks 142 . Studies have shown that mice infected with Heligmosomoides polygyrus bakeri will change the composition of gut microbiota by increasing SCFAs and ultimately resulting in reduced inflammation in dust mites‐induced asthma models 143 …”

“…Researchers have discovered that helminths affect the composition of gut microbiota and indirectly affect the lung immune response and prevent asthma attacks. 142 Studies have shown that mice infected with Heligmosomoides polygyrus bakeri will change the composition of gut microbiota by increasing SCFAs and ultimately resulting in reduced inflammation in dust mites‐induced asthma models. 143 …”

Mechanism of Action of Melatonin as a Potential Adjuvant Therapy in Inflammatory Bowel Disease and Colorectal Cancer

“…Several harmful bacteria were found to be responsible for IBD pathogenesis, such as Firmicutes (abundant in bare sand), Proteobacteria , and Roseburia spp., including Roseburia faecis and Roseburia intestinalis [ 19 ]. The relative increase of these species in the gut, leads to their attachment to colonic mucosa, thus affecting and increasing its permeability [ 20 ]. As for CRC, the exact pathogenesis is unclear and needs further investigation [ 21 ].…”