Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Although lactobacilli and bifidobacteria produce beneficial lactic and short-chain fatty acids in the mammalian gut, the significance of intestinal Escherichia coli producing these acids is debatable. Taking a Koch’s postulates approach in reverse, we define Escherichia coli as health-promoting for naturally colonizing the gut of healthy mice and protecting them against intestinal colonization and concomitant mortality by Pseudomonas aeruginosa. Reintroduction of faecal bacteria and E. coli in antibiotic-treated mice establishes a high titre of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Strikingly, high sugar concentration favours E. coli fermentation to lactic and acetic acid and inhibits P. aeruginosa growth and virulence in aerobic cultures and in a model of aerobic metabolism in flies, while dietary vegetable fats - not carbohydrates or proteins - favour E. coli fermentation and protect the host in the anaerobic mouse gut. Thus E. coli metabolic output is an important indicator of resistance to infection. Our work may also suggest that the lack of antimicrobial bacterial metabolites in mammalian lungs and wounds allows P. aeruginosa to be a formidable microbe at these sites.

Gut 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 that Escherichia coli naturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization by Pseudomonas aeruginosa and concomitant mortality. Reintroduction of fecal bacteria and E. coli establishes a high titer of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favours E. coli fermentation to lactic acid and P. aeruginosa growth inhibition. To the contrary, low sugars allow P. aeruginosa to produce the oxidative agent pyocyanin that inhibits E. coli growth. Our results provide an explanation as to why P. aeruginosa doesn't commonly infect the human gut, despite being a formidable microbe in lung and wound infections. Author SummaryHere we interrogate the conundrum as to why Pseudomonas aeruginosa is not a clinical problem in the intestine as opposed to other tissues. P. aeruginosa interacts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induce P. aeruginosa virulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence of P. aeriginosa. We reasoned that P. aeruginosa might be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such as Escherichia coli. Therefore, we dissected the antagonism between E. coli and P. aeruginosa and 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 commensal E. coli, in addition to lactic acid bacteria, imposing a gut environment conducive to P. aeruginosa infection. Moreover, commensal E. coli provides an explanation as to why P. aeruginosa doesn't commonly infect the human gut, despite being a formidable microbe in lung and wound infections.Antibiotics can also greatly affect microbiota diversity and promote dysbiosis. Early in life, antibiotic treatment can modulate the development of gut microbiota in children (Tanaka et al. 2009). In children and adults, opportunistic pathogens can take advantage of the antibiotic effect on commensal bacteria to infect the gut (Chang et al. 2008). One such pathogen is the gram-negative human opportunistic bacterium Pseudomonas aeruginosa, one of the most frequent species in hospital-acquired infections (Markou and Apidianakis 2013). While not a common clinical problem in the gut, P. aeruginosa colonizes the gastrointestinal tract of many hospitalized patients and to a lesser extent of healthy individuals (Ohara and Itoh 2003, Sh...