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

Chakraborty, Rajrupa; Lam, Vy; Kommineni, Sushma; Stromich, Jeremiah; Hayward, Michael A.; Kristich, Christopher J.; Salzman, Nita H.

doi:10.1128/iai.00674-18

Cited by 37 publications

(26 citation statements)

References 87 publications

(82 reference statements)

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“…Finally, the majority of studies have focused on susceptibility to infection with specific pathogens such as Clostridium difficile, enterococci spp., salmonella spp., EPE, etc. and not the overall impact on the microbiota [9,11,12,14,15].…”

Section: Discussionmentioning

confidence: 98%

Effects of Antibiotics on the Intestinal Microbiota of Mice

Hertz

Budding²,

Lugt-Degen³

et al. 2020

Antibiotics

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Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community and there are examples of how antibiotic usage lead to colonization with resistant bacteria [e.g., dicloxacillin usage selecting for ESBL-producing E. coli carriage], as shown by Hertz et al. Here, we investigated the impact of five antibiotics [cefotaxime, cefuroxime, dicloxacillin, clindamycin, and ciprofloxacin] on the intestinal microbiota in mice. Five different antibiotics were each given to groups of five mice. The intestinal microbiotas were profiled by use of the IS-pro analysis; a 16S–23S rDNA interspace [IS]-region-based profiling method. For the mice receiving dicloxacillin and clindamycin, we observed dramatic shifts in dominating phyla from day 1 to day 5. Of note, diversity increased, but overall bacterial load decreased. For ciprofloxacin, cefotaxime, and cefuroxime there were few overall changes. We speculate that antibiotics with efficacy against the abundant anaerobes in the gut, particularly Bacteroidetes, can in fact be selected for resistant bacteria, disregarding the spectrum of activity.

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Section: Discussionmentioning

confidence: 98%

Effects of Antibiotics on the Intestinal Microbiota of Mice

Hertz

Budding²,

Lugt-Degen³

et al. 2020

Antibiotics

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“…In keeping with this conclusion, Chakraborty et al . recently reported that intestinal proliferation is required for translocation of enterococci upon ceftriaxone treatment 25 . Epidemiological studies have also reported an association between VRE intestinal domination and bloodstream infection 4–6 .…”

Section: Discussionmentioning

confidence: 99%

Intestinal translocation of enterococci requires a threshold level of enterococcal overgrowth in the lumen

Archambaud

Derré-Bobillot

Lapaque

et al. 2019

Sci Rep

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Enterococci are subdominant members of the human gastrointestinal microbiota. Enterococcus faecalis is generally harmless for healthy individuals, but it can cause a diverse range of infections in immunodeficient or elderly patients with severe underlying diseases. In this study, we analysed the levels of intestinal translocation of indigenous enterococci in C57BL/6, CF-1 and CX3CR1 −/− mice upon clindamycin antibiotic-induced dysbiosis. We found that C57BL/6 was the most permissive model for enterococcal translocation and that initiation of E . faecalis translocation coincided with a threshold of enterococcal colonisation in the gut lumen, which once reached, triggered E . faecalis dissemination to deeper organs. We showed that the extent to which E . faecalis clinical strain VE14821 competed with indigenous enterococci differed between the C57BL/6 and CX3CR1 −/− models. Finally, using a simplified gnotobiotic model, we observed E . faecalis crossing an intact intestinal tract using intestinal epithelial cells as one route to reach the lamina propria. Our study opens new perspectives for assessing the effect of various immunodeficiencies and for investigating mechanisms underlying enterococcal translocation.

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“…Of note, exposure to ceftriaxone did not affect TJ protein expression, fecal albumin, or permeability to FITC-dextran. 46 Oral antibiotics were shown to induce colonic goblet cell-associated antigen passages that enabled translocation of live bacteria to MLN, which continued for~5 days after antibiotic withdrawal. 47 Thus, antibiotics may disrupt colonization resistance and physiological homeostatic processes, allowing for transient dissemination of bacteria even without overt intestinal pathology.…”

Section: Induced Gut Barrier Disruption and Translocationmentioning

confidence: 99%

“…39 Overall, enterococci and lactobacilli appear to be predominant genera translocating under pathologic conditions. 46…”

Section: Spontaneous Gut Commensal Disseminationmentioning

confidence: 99%

Mechanisms and consequences of gut commensal translocation in chronic diseases

et al. 2019

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Humans and other mammalian hosts have evolved mechanisms to control the bacteria colonizing their mucosal barriers to prevent invasion. While the breach of barriers by bacteria typically leads to overt infection, increasing evidence supports a role for translocation of commensal bacteria across an impaired gut barrier to extraintestinal sites in the pathogenesis of autoimmune and other chronic, non-infectious diseases. Whether gut commensal translocation is a cause or consequence of the disease is incompletely defined. Here we discuss factors that lead to translocation of live bacteria across the gut barrier. We expand upon our recently published demonstration that translocation of the gut pathobiont Enterococcus gallinarum can induce autoimmunity in susceptible hosts and postulate on the role of Enterococcus species as instigators of chronic, noninfectious diseases.

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

Cited by 37 publications

References 87 publications

Effects of Antibiotics on the Intestinal Microbiota of Mice

Effects of Antibiotics on the Intestinal Microbiota of Mice

Intestinal translocation of enterococci requires a threshold level of enterococcal overgrowth in the lumen

Mechanisms and consequences of gut commensal translocation in chronic diseases

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