With the increasing and extensive research on gut microbes in recent years, it has been confirmed that gut microbes are not only an important component of the local immune barrier in the gastrointestinal mucosa, but also play an unexpected role in the regulation of the systemic immune system. However, the role of intestinal microbes in bacterial pneumonia is still unclear. To this end, it was confirmed that the intestinal flora of mice plays an important role in maintaining normal immune function of the body against Streptococcus pneumoniae pneumonia, and the study was published online in the October 2015 issue of Gut. The researchers first used antimicrobials to disrupt the intestinal flora of C57BL/6 mice as a test group and then infected them intranasally with Streptococcus pneumoniae. They observed the bacterial counts in the lungs and blood, cytokine levels, and survival rate of mice after infection, and further investigated the organ-protective effects of intestinal flora in Streptococcus pneumoniae sepsis, the effects and mechanisms of action on macrophage phagocytosis in the lungs, and the protective effects of fecal bacteria transplantation (FMT) on infected mice. It was found that the number of bacteria in the lungs after 6h of infection and the number of bacteria in the blood after 48h of infection were significantly higher in the test group of mice compared with the control group. The levels of IL-1β, IL-6 and CXCL-1 in the lungs were increased and the levels of TNF-α and IL-10 were decreased after 6h of infection, and the mortality rate was significantly higher than that of the control group. After FMT treatment in the test group of mice, all of these indexes were significantly improved and approached the level of the control group, confirming the protective effect of normal intestinal flora on the host in severe Streptococcus pneumoniae infection. In addition, by conducting histological semi-quantitative studies on the organs of lung, liver and spleen of mice at different time periods after infection, the researchers found that the degree of inflammatory damage in each organ was significantly higher in the test group than in the control group, further confirming the organ-protective effect of intestinal normal microorganisms. Accordingly, the investigators hypothesized that there may be an intestinal-pulmonary axis linking intestinal microorganisms to lung macrophages that serves as a key to initiate the pulmonary immune response after pathogen invasion. The phagocytic activity of lung macrophages in the test group of mice in this study was significantly lower than that of the control group, associated with their decreased response to lipophosphate (LTA) and lipopolysaccharide (LPS). Genome-wide mapping studies of macrophages showed that the expression of some metabolic pathways was upregulated in lung macrophages of mice with disrupted normal intestinal flora. This alteration was associated with a decreased macrophage response to LTA and LPS, which in turn led to diminished phagocytosis of Streptococcus pneumoniae. Although it is prudent to directly extrapolate findings from animal studies to humans, the results of this study suggest that the gut microbiota is beneficial not only in defending against localized intestinal infections but also in modulating the systemic immune response and initiating alveolar macrophage defense against Streptococcus pneumoniae pneumoniae via the enteropulmonary axis. In conclusion, the investigators concluded that the clinical use of broad-spectrum antimicrobials may disrupt the intestinal microecological balance and weaken the intrinsic infection defense of the organism. Furthermore, the use of microecological agents or FMT to re-establish intestinal microecology in the treatment of severe infections offers a new avenue to improve patient prognosis.