Antibiotic-Induced Perturbations of the Intestinal Microbiota Alter Host Susceptibility to Enteric Infection

Abstract

Intestinal microbiota comprises microbial communities that reside in the gastrointestinal tract and are critical to normal host physiology. Understanding the microbiota's role in host response to invading pathogens will further advance our knowledge of host-microbe interactions. Salmonella enterica serovar Typhimurium was used as a model enteric pathogen to investigate the effect of intestinal microbiota perturbation on host susceptibility to infection. Antibiotics were used to perturb the intestinal microbiota. C57BL/6 mice were treated with clinically relevant doses of streptomycin and vancomycin in drinking water for 2 days, followed by oral infection with Salmonella enterica serovar Typhimurium. Alterations in microbiota composition and numbers were evaluated by fluorescent in situ hybridization, differential plating, and Sybr green staining. Antibiotics had a dose-dependent effect on intestinal microbiota composition. The chosen antibiotic regimen did not significantly alter the total numbers of intestinal bacteria but altered the microbiota composition. Greater preinfection perturbations in the microbiota resulted in increased mouse susceptibility to Salmonella serovar Typhimurium intestinal colonization, greater postinfection alterations in the microbiota, and more severe intestinal pathology. These results suggest that antibiotic treatment alters the balance of the microbial community, which predisposes the host to Salmonella serovar Typhimurium infection, demonstrating the importance of a healthy microbiota in host response to enteric pathogens.

Antimicrobials, Gut Microbiota and Immunity in Chickens

“…In addition, the evidence is increasing that gut microbiota plays an important role in health, immunity and disease prevention (Dibner et al, 2008;Sekirov et al, 2008). The published data (Turnbaugh et al, 2006;Caesar et al, 2010;Wlodarska and Finlay, 2010) supported the view that altered microbiota is linked to obesity, inflammatory bowel disease (IBD), atherosclerosis and cancer.…”

Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice

“…26 Most importantly, the commensal flora is able to keep opportunistic pathogens at bay. 7,37 This defensive capacity is most prevalent following a course of antibiotics taken by the host. Although protection from infection can be attributed to a single commensal bacterial species in some cases, it is now well accepted that the overall diversity of the microbial flora is the best indicator of protective capacity.…”

“…Correlations between altered microbiome and disease state has been suggested in several conditions such as obesity, inflammatory bowel disease (IBD), allergy, antibiotic associated diarrhea, or opportunistic pathogen infection. [7][8][9][10] In particular the antibiotic induced alterations of the gut microbiome can pose a major health problem due to the significant and long lasting changes to the microbial community following treatment. Taking antibiotics can promote the reservoir of antibiotic resistance genes and the emergence of highly resistant strains of bacteria.…”

The Gut Microbiota: Ecology and Function

“…This function is not simply a matter of total bacterial abundance. The type of bacteria present is important because disruption of the composition of the microbiota without a reduction in total levels led to increased susceptibility to enteric infection by Salmonella and other enteric pathogens (Sekirov et al, 2008). The mechanistic explanation for this is yet to be defined; however, it is expected that it is either the result of competitive exclusion by commensal bacteria or the result of immune regulation by other bacteria.…”

“…A normal mouse microbiota confers resistance to Salmonella-induced gastroenteritis and shifting of the normal microbiota creates increased susceptibility to Salmonella (Sekirov et al, 2008). This function is not simply a matter of total bacterial abundance.…”