Commensal acidification of specific gut regions produces a protective priority effect against enteropathogenic bacterial infection.

Abstract

The commensal microbiome has been shown to protect against newly introduced enteric pathogens in multiple host species, a phenomenon known as a priority effect. Multiple mechanisms can contribute to this protective priority effect, including antimicrobial compounds, nutrient competition, and pH changes. In Drosophila melanogaster, Lactiplantibacillus plantarum has been shown to protect against enteric pathogens. However, the strains of L. plantarum studied were derived from laboratory flies or non-fly environments and have been found to be unstable colonizers of the fly gut that mainly reside on the food. To study the priority effect using a naturally occurring microbial relationship, we isolated a wild fly-derived strain of L. plantarum that stably colonizes the fly gut in conjunction with a common enteric pathogen, Serratia marcescens. Flies stably associated with the L. plantarum strain were more resilient to oral Serratia marcescens infection as seen by longer life span and lower S. marcescens load in the gut. Through in vitro experiments, we found that L. plantarum inhibits S. marcescens growth due to acidification. We used gut imaging with pH indicator dyes to show that L. plantarum reduces the gut pH to levels that restrict S. marcescens growth in vivo. In flies colonized with L. plantarum prior to S. marcescens infection, L. plantarum and S. marcescens are spatially segregated in the gut, and S. marcescens is less abundant where L. plantarum heavily colonizes, indicating that acidification of specific gut regions is a mechanism of a protective priority effect.IMPORTANCEThe gut microbiomes of animals harbor an incredible diversity of bacteria, some of which can protect their hosts from invasion by enteric pathogens. Understanding the mechanisms behind this protection is essential for developing precision probiotics to support human and animal health. This study used Drosophila melanogaster as a model system due to its low cost, experimentally tractable gut microbiome, and overlap with bacterial species found in mammals. While resident microbes can protect hosts through various means, including toxin production and immune stimulation, we found that acidification was sufficient to limit a pathogen that normally reduces life span. Remarkably, specific gut regions are acidified either by host mechanisms or by the resident bacterium, Lactiplantibacillus plantarum, highlighting joint microbial and host control of gut chemistry. These findings are broadly relevant to microbiology and gut health, providing insight into how hosts may manage pathogens through their symbiotic microbiota.