Journal Article

Microbiota-mediated colonization resistance against intestinal pathogens

Pamer, Eric G., Buffie, Charlie G.

2013

Overview

Key Points Antibiotic treatment disrupts the native intestinal microbiota and favours infection with and the proliferation of antibiotic-resistant intestinal pathogens. Clinically important antibiotic-resistant pathogens include vancomycin-resistant Enterococcus spp., various Enterobacteriaceae and Clostridium difficile . The intestinal microbiota influences the development, the maintenance and the function of the innate and adaptive immune systems. Host immune function is decreased in the intestines following antibiotic therapy, and antibiotic-treated hosts are susceptible to intestinal infection. Microbiota-derived bacterial populations and products that enhance immune defence against intestinal pathogens are being identified. However, the precise bacterial sources of many immunomodulatory molecules remain unclear and, conversely, the molecular mechanisms by which most probiotics restore immunity have yet to be elucidated. In addition to indirectly enhancing colonization resistance by stimulating host immune defences, bacterial populations can directly suppress intestinal pathogens by competitive exclusion and by antimicrobial activities. The commensal populations that are responsible for direct antagonism of pathogens and indirect, immune-mediated colonization resistance may be closely related and difficult to distinguish. Microbiota-derived bacterial populations and products, a subset of which enhance immune defence, can also promote intestinal inflammation, whereas other microbiota components restrain effector responses and promote tolerance. Manipulation of the intestinal microbiota to prevent and to treat some intestinal infections, such as C. difficile , shows promise in human patients and animal models of infection. However, the specific contributions of the individual bacterial populations that constitute the consortia transferred in such studies remain mostly undefined. Colonization resistance — protection from exogenous pathogens by commensal bacteria — can be mediated by direct antagonism and by indirect effects on the host immune response. This Review outlines our current knowledge of immune-mediated colonization resistance against clinically relevant, antibiotic-resistant intestinal pathogens and how insights into commensal bacterial species and their mechanisms might be therapeutically used to restore resistance. Commensal bacteria inhabit mucosal and epidermal surfaces in mice and humans, and have effects on metabolic and immune pathways in their hosts. Recent studies indicate that the commensal microbiota can be manipulated to prevent and even to cure infections that are caused by pathogenic bacteria, particularly pathogens that are broadly resistant to antibiotics, such as vancomycin-resistant Enterococcus faecium , Gram-negative Enterobacteriaceae and Clostridium difficile . In this Review, we discuss how immune- mediated colonization resistance against antibiotic-resistant intestinal pathogens is influenced by the composition of the commensal microbiota. We also review recent advances characterizing the ability of different commensal bacterial families, genera and species to restore colonization resistance to intestinal pathogens in antibiotic-treated hosts.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/2499 / 631/250/255/1318 / 631/250/255/1911 / 631/250/347 / 631/326/41/2533 / Animals / Anti-Bacterial Agents - pharmacology / Antibiotic resistance / Antibiotics / Bacteria / Bacteria - drug effects / Bacteria - genetics / Bacteria - immunology / Bacteria - pathogenicity / Biomedicine / Clostridium difficile / Colonization / Drug resistance / Drug resistance in microorganisms / Drug Resistance, Microbial - genetics / Drug Resistance, Microbial - immunology / Drug therapy / Enterobacteriaceae / Enterococcus faecium / Gastrointestinal diseases / Genetic aspects / Health aspects / Humans / Immunity, Mucosal / Immunology / Infections / Inflammation - immunology / Inflammation - microbiology / Intestines - immunology / Intestines - microbiology / Microbiota / Microbiota (Symbiotic organisms) / Pathogens / review-article / Risk factors / Salmonella