Background Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels. Results Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice. Conclusions Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.

Background: Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known as how the airway microbiome affected airway immune development. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Results: Intranasal inoculation of S. epidermidis AIT01 accompanied the active recruitment of neutrophils and monocytes into mouse lungs on the murine model. The recruitment of the immune cells resulted in the complete protection of the murine host against Pseudomonas aeruginosa respiratory infection. Interestingly, an AIT01-secreted protein identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified protein conferred significant resistance against other additional airway infections of Gram-negative pathogens or influenza A virus. Moreover, single cell RNA-seq analysis using mouse lung cells revealed that transcription of genes involved in cytokine production, phagocytosis, chemotaxis, and immune cell migration was considerably upregulated in neutrophils and monocytes in response to the treatment with the protein. Conclusions: Our results illustrate how an indigenous nasal microbe and its secretory protein can extensively instigate an innate immune defense. We also suggest a promising prophylactic option for airway infections in the era of global pandemics. Keywords: Staphylococcus epidermidis, human nasal microbiome, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), innate immune defense