DefiningEscherichia colias a health-promoting microbe against intestinalPseudomonas aeruginosa

Abstract

AbstractGut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Koch’s postulates approach in reverse to define health-promoting microbes we find thatEscherichia colinaturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization byPseudomonas aeruginosaand concomitant mortality. Reintroduction of fecal bacteria andE. coliestablishes a high titer ofE. coliin the host intestine and increases defence againstP. aeruginosacolonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favoursE. colifermentation to lactic acid andP. aeruginosagrowth inhibition. To the contrary, low sugars allowP. aeruginosato produce the oxidative agent pyocyanin that inhibitsE. coligrowth. Our results provide an explanation as to whyP. aeruginosadoesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections.Author SummaryHere we interrogate the conundrum as to whyPseudomonas aeruginosais not a clinical problem in the intestine as opposed to other tissues.P. aeruginosainteracts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induceP. aeruginosavirulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence ofP. aeriginosa. We reasoned thatP. aeruginosamight be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such asEscherichia coli. Therefore, we dissected the antagonism betweenE. coliandP. aeruginosaand the effect of a conventional, a fat-, a carbohydrate-and a protein-based diet in intestinal dysbiosis. Our findings support the notion that an unbalanced diet or antibiotics induces gut dysbiosis by the elimination of commensalE. coli, in addition to lactic acid bacteria, imposing a gut environment conducive toP. aeruginosainfection. Moreover, commensalE. coliprovides an explanation as to whyP. aeruginosadoesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections.