Shifting the balance: antibiotic effects on host–microbiota mutualism

• Published in: Nature reviews. Microbiology Vol. 9; no. 4; pp. 233 - 243
• Main Authors: Finlay, B. Brett, Willing, Benjamin P, Russell, Shannon L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2011; Nature Publishing Group
• Subjects: 22; 41; 631/250/347; 631/326/22/1290; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Autism; Bacteria; Bacteria - drug effects; Bacteria - metabolism; Bacterial diseases; Bacterial infections; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Biomass; Biomedical and Life Sciences; Diabetes; Disease; Disease Susceptibility; Enterocolitis, Pseudomembranous - etiology; Epidemiology; Fatty Acids, Volatile - metabolism; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - immunology; Gastrointestinal Tract - microbiology; Health aspects; Homeostasis; Homeostasis - drug effects; Host-Pathogen Interactions - drug effects; Humans; Immunity, Mucosal; Infectious Diseases; Inflammatory bowel disease; Life Sciences; Medical Microbiology; Metagenome - drug effects; Microbial Interactions - drug effects; Microbiology; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Mutualism; Parasitology; Pathogens; review-article; Salmonella; Virology; Canada
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro2536

Key Points
Antibiotics have substantial direct and indirect effects on the intestinal microbiota; although some of the changes disappear soon after cessation of the antibiotic treatment, other changes remain indefinitely. Owing to their substantial effects on the microbiota, antibiotics have been used experimentally to identify groups of bacteria that correlate with changes in immunity and disease susceptibility.
Throughout the course of evolution, the host has become dependent on its microbiota for many functions, including the maintenance of intestinal immune homeostasis. Changes in the microbiota that are induced by antibiotic treatment and are important to immunity include the loss of bacterial ligands that are recognized by the host, changes in the metabolites that are produced by the microbiota and the loss of specific bacterial signals.
Studies using antibiotics have revealed that the microbiota not only contributes to development, but also is required for the maintenance of immune function. Many changes in immunity have been observed in response to antibiotics, including reduced secretion of antimicrobial peptides and changes in T helper cell populations. Changes in immunity that result from antibiotic treatment result in increased susceptibility to infection.
Antibiotics have been used to implicate the gastrointestinal microbiota in a number of systemic biological processes, including elements of systemic immunity and extra-intestinal disease susceptibility. Antibiotics have linked the intestinal microbiota to models of allergies, autism, metabolic syndrome and multiple sclerosis.
There are several challenges that need to be considered when using antibiotics to study host–microbial interactions. Direct effects on the immune system, reproducibility with respect to the duration and number of antibiotic exposures, antibiotic resistance and individualized responses to the same treatment all influence the outcome of antibiotic studies. Currently, most antibiotic studies remain correlative owing to the lack of targeted approaches available.
There is a need to develop strategies to mitigate the effects of antibiotics on the immune system. Promising approaches include bacteriotherapy and exogenous immune activation with bacterial ligands.
The use of antibiotics is making lasting alterations to the long-term relationship between a host and its microbiota. Willing, Russell and Finlay describe how these changes can result in the disruption of immune homeostasis and in increased susceptibility to disease.
Antibiotics have been used effectively as a means to treat bacterial infections in humans and animals for over half a century. However, through their use, lasting alterations are being made to a mutualistic relationship that has taken millennia to evolve: the relationship between the host and its microbiota. Host–microbiota interactions are dynamic; therefore, changes in the microbiota as a consequence of antibiotic treatment can result in the dysregulation of host immune homeostasis and an increased susceptibility to disease. A better understanding of both the changes in the microbiota as a result of antibiotic treatment and the consequential changes in host immune homeostasis is imperative, so that these effects can be mitigated.