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Ceftriaxone Administration Disrupts Intestinal Homeostasis, Mediating Noninflammatory Proliferation and Dissemination of Commensal Enterococci.

ABSTRACT: Enterococci are Gram-positive commensals of the mammalian intestinal tract and harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of colonization resistance in humans by antibiotics allows enterococci to proliferate in the gut and cause disseminated infections. In this study, we used Enterococcus faecalis (EF)-colonized mice to study the dynamics of enterococci, commensal microbiota, and the host in response to systemic ceftriaxone administration. We found that the mouse model recapitulates intestinal proliferation and dissemination of enterococci seen in humans. Employing a ceftriaxone-sensitive strain of enterococci (E. faecalis JL308), we showed that increased intestinal abundance is critical for the systemic dissemination of enterococci. Investigation of the impact of ceftriaxone on the mucosal barrier defenses and integrity suggested that translocation of enterococci across the intestinal mucosa was not associated with intestinal pathology or increased permeability. Ceftriaxone-induced alteration of intestinal microbial composition was associated with transient increase in the abundance of multiple bacterial operational taxonomic units (OTUs) in addition to enterococci, for example, lactobacilli, which also disseminated to the extraintestinal organs. Collectively, these results emphasize that ceftriaxone-induced disruption of colonization resistance and alteration of mucosal homeostasis facilitate increased intestinal abundance of a limited number of commensals along with enterococci, allowing their translocation and systemic dissemination in a healthy host.

SUBMITTER: Chakraborty R

PROVIDER: S-EPMC6246901 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adult Drosophila melanogaster raised in the absence of symbiotic bacteria have fewer intestinal stem cell divisions and a longer life span than their conventionally reared counterparts. However, we do not know if increased stem cell divisions are essential for symbiont-dependent regulation of longevity. To determine if individual symbionts cause aging-dependent death in Drosophila, we examined the impacts of common symbionts on host longevity. We found that monoassociation of adult Drosophila with Lactobacillus plantarum, a widely reported fly symbiont and member of the probiotic Lactobacillus genus, curtails adult longevity relative to germfree counterparts. The effects of Lactobacillus plantarum on life span were independent of intestinal aging. Instead, we found that association with Lactobacillus plantarum causes an extensive intestinal pathology within the host, characterized by loss of stem cells, impaired epithelial renewal, and a gradual erosion of epithelial ultrastructure. Our study uncovers an unknown aspect of Lactobacillus plantarum-Drosophila interactions and establishes a simple model to characterize symbiont-dependent disruption of intestinal homeostasis.IMPORTANCE Under homeostatic conditions, gut bacteria provide molecular signals that support the organization and function of the host intestine. Sudden shifts in the composition or distribution of gut bacterial communities impact host receipt of bacterial cues and disrupt tightly regulated homeostatic networks. We used the Drosophila melanogaster model to determine the effects of prominent fly symbionts on host longevity and intestinal homeostasis. We found that monoassociation with Lactobacillus plantarum leads to a loss of intestinal progenitor cells, impaired epithelial renewal, and disruption of gut architecture as flies age. These observations uncover a novel phenotype caused by monoassociation of a germfree host with a common symbiont and establish a simple model to characterize symbiont-dependent loss of intestinal homeostasis.

Dataset Information

Ceftriaxone Administration Disrupts Intestinal Homeostasis, Mediating Noninflammatory Proliferation and Dissemination of Commensal Enterococci.

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