Perturbation of the Small Intestine Microbial Ecology by Streptomycin Alters Pathology in a Salmonella enterica Serovar Typhimurium Murine Model of Infection

Abstract

The small intestine is an important site of infection for many enteric bacterial pathogens, and murine models, including the streptomycin-treated mouse model of infection, are frequently used to study these infections. The environment of the mouse small intestine and the microbiota with which enteric pathogens are likely to interact, however, have not been well described. Therefore, we compared the microbiota and the concentrations of short-chain fatty acids (SCFAs) present in the ileum and cecum of streptomycin-treated mice and untreated controls. We found that the microbiota in the ileum of untreated mice differed greatly from that of the cecum of the same mice, primarily among families of the phylum Firmicutes. Upon treatment with streptomycin, substantial changes in the microbial composition occurred, with a marked loss of population complexity. Characterization of the metabolic products of the microbiota, the SCFAs, showed that formate was present in the ileum but low or not detectable in the cecum while butyrate was present in the cecum but not the ileum. Treatment with streptomycin altered the SCFAs in the cecum, significantly decreasing the concentration of acetate, propionate, and butyrate. In this work, we also characterized the pathology of Salmonella infection in the ileum. Infection of streptomycin-treated mice with Salmonella was characterized by a significant increase in the relative and absolute levels of the pathogen and was associated with more severe ileal inflammation and pathology. Together these results provide a better understanding of the ileal environment in the mouse and the changes that occur upon streptomycin treatment.

Which species are in your feces?

“…These changes in the flora allowed normally resistant mice to become susceptible to VRE infection. Thus, the composition of the bacterial flora was critical in restraining the outgrowth of potentially pathogenic species, a pattern that has also been observed in animals with S. typhimurium infection (19)(20)(21).…”

“…The regulatory role of commensal bacteria may be to activate the intestinal immune response to control potentially pathogenic bacteria, as it has been shown that colonization of germ-free mice with a defined flora leads to the expression of several antimicrobial peptides, including the secreted C-type lectin regenerating islet-derived IIIγ (REGIIIγ), which is directly toxic to Gram-positive commensal and pathogenic bacteria (15,16), and the goblet cell-specific protein resistin-like molecule-β (RELMβ) (17). In addition, antibiotic treatment of mice leads to a reduction in total numbers of bacteria, loss of REGIIIγ and RELMβ expression (11,18), and increased susceptibility to outgrowth of, or infection with, intestinal bacterial pathogens such as Salmonella typhimurium (19)(20)(21) and VRE (11). Thus, the commensal flora are a critical component in maintaining the steady state as well as in preventing the outgrowth of potentially pathogenic species.…”

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

“…Enhanced susceptibility to infection has frequently been associated with the negative impacts of broadspectrum antimicrobials on the gut microbiota (21,27,31). With respect to CDAD and antibiotic treatment, the strategies that have been used to address this issue include supplementation of the diet with probiotics (26,32) and fecal transplantation (33).…”

From Structure to Function: the Ecology of Host-Associated Microbial Communities

“…Additionally, they impact fat and glucose utilization as well as the lymphocyte response to intestinal injury (152,220,331). Host-associated microbes also contribute to host susceptibility to inflammatory bowel disease and infection-mediated diseases (103,288). Furthermore, these bacteria may contribute to host susceptibility to type 1 diabetes, allergies, and cancer (304,354,368).…”