Bacterial Swarmers exhibit a Protective Response to Intestinal Stress

Abstract

Bacterial swarming is a conserved and distinct form of bacterial motility that allows for 29 rapid migration over a surface. Swarming motility is often oppositely regulated and 30 antagonistic to biofilm formation 1 . To-date, while bacterial biofilms have been associated 31 with pathogenesis and pathobiology of human diseases (e.g., infections, inflammation and 32 cancer) 2-4 , there are very few examples of swarming behaviors that uniquely define or align 33 with human pathophysiology (e.g., antibiotic resistance) 5,6,7 . Here we report that bacterial 34 swarming is highly predictive of the presence of intestinal stress in mice, pigs and humans. 35 Using a modified agar plate assay, we isolated from murine feces a novel Enterobacter 36 hyperswarming strain, SM3 that demonstrated significant protection from intestinal 37 inflammation and promoted restitution in a mouse model of colitis. As opposed to bacterial 38 biofilms 8 , we report that the swarming phenotype protects against intestinal inflammation 39 in mice. Mechanistically, commensal swarming strains rapidly consume oxygen in vitro and 40 in vivo, leading to a favorable anaerobic environment conducive to the growth of beneficial 41 anaerobes. The swarming property of bacteria rather than the individual strains 42 themselves, independently lends the ability to protect and heal from intestinal 43 inflammation. This work identifies a new paradigm in which intestinal stress, specifically 44 inflammation, allows for emergence of swarming bacteria, which in turn act to suppress 45 inflammation via mechanisms that are associated in part with oxygen depletion and bloom 46 of beneficial anaerobes. 47

Western-style diet impedes colonization and clearance of gut bacterial pathogens

“…While adaptive immunity is required to clear epithelial-adherent C. rodentium, elimination of this pathogen from the outer mucus and lumen is thought to result from C. rodentium being outcompeted by commensal microbiota [9]. Hence, we hypothesized that inability of WSD-fed mice to eliminate C. rodentium, might reflect low microbiota density, altered species composition, and/or lack of inflammation-induced changes in microbiota, which may help clear oxygen-using pathogens [25]. To test this hypothesis, we measured C. rodentium-induced changes in microbiota infection via qPCR and 16s rRNA sequencing ( Figure 5 and Figure S5).…”