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Antibiotic induced changes in the GI tract
Int J Microbiol. 2011;2011:312956. doi: 10.1155/2011/312956. Epub 2011 Jan 24.
Assessment of bacterial antibiotic resistance
transfer in the gut.
Schjørring S1, Krogfelt KA.
Author information
Abstract
We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract.
During the last decades, the emergence of antibiotic resistant strains and treatment failures of
bacterial infections have increased the public awareness of antibiotic usage. The use of broad
spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the
emergence of multiresistant bacteria, which results in a vicious circle of treatments and
emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive
reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance
genes. The increased use of fermented food products and probiotics, as food supplements and
health promoting products containing massive amounts of bacteria acting as either donors
and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the
emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic
resistance gene transfer occurring in the gut.
Supplemental Content
Infect Immun. 2012 Jan;80(1):62-73. doi: 10.1128/IAI.05496-11. Epub 2011 Oct 17.
Profound alterations of intestinal
microbiota following a single dose of
clindamycin results in sustained
susceptibility to Clostridium difficileinduced colitis.
Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A, Ubeda C, Xavier J,
Pamer EG.
Source
Infectious Diseases Service, Department of Medicine, Lucille Castori Center for Microbes,
Inflammation and Cancer, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer
Center, New York, New York, USA
Abstract
Antibiotic-induced changes in the intestinal microbiota predispose mammalian hosts to
infection with antibiotic-resistant pathogens. Clostridium difficile is a Gram-positive
intestinal pathogen that causes colitis and diarrhea in patients following antibiotic treatment.
Clindamycin predisposes patients to C. difficile colitis. Here, we have used Roche-454 16S
rRNA gene pyrosequencing to longitudinally characterize the intestinal microbiota of mice
following clindamycin treatment in the presence or absence of C. difficile infection. We show
that a single dose of clindamycin markedly reduces the diversity of the intestinal microbiota
for at least 28 days, with an enduring loss of ca. 90% of normal microbial taxa from the
cecum. Loss of microbial complexity results in dramatic sequential expansion and contraction
of a subset of bacterial taxa that are minor contributors to the microbial consortium prior to
antibiotic treatment. Inoculation of clindamycin-treated mice with C. difficile (VPI 10463)
spores results in rapid development of diarrhea and colitis, with a 4- to 5-day period of
profound weight loss and an associated 40 to 50% mortality rate. Recovering mice resolve
diarrhea and regain weight but remain highly infected with toxin-producing vegetative C.
difficile bacteria and, in comparison to the acute stage of infection, have persistent, albeit
ameliorated cecal and colonic inflammation. The microbiota of "recovered" mice remains
highly restricted, and mice remain susceptible to C. difficile infection at least 10 days
following clindamycin, suggesting that resolution of diarrhea and weight gain may result from
the activation of mucosal immune defenses.
Supplemental Content
J Clin Microbiol. 2004 Mar;42(3):1203-6.
Antibiotic-associated diarrhea accompanied
by large-scale alterations in the
composition of the fecal microbiota.
Young VB, Schmidt TM.
Source
Department of Microbiology and Molecular Genetics, Infectious Diseases Unit, National
Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan
48824, USA. [email protected]
Abstract
Alterations in the diversity of the gut microbiota are believed to underlie the development of
antibiotic-associated diarrhea (AAD). A molecular phylogenetic analysis was performed to
document temporal changes in the diversity of fecal bacteria of a patient who developed
AAD. Antibiotic administration was associated with distinct changes in the diversity of the
gut microbiota, including a marked decrease in the prevalence of butyrate-producing bacteria.
Following the discontinuation of the antibiotic, resolution of diarrhea was accompanied by a
reversal of these changes, providing the first direct evidence linking changes in the
community structure of the gastrointestinal bacteria with the development of AAD.
Comment in
•
Antibiotic-associated diarrhea: it's all about the butyrate. [Rev Gastroenterol Disord.
2004]
Supplemental Content
FEMS Microbiol Lett. 2012 Nov;336(1):11-6. doi: 10.1111/j.1574-6968.2012.02647.x. Epub
2012 Sep 18.
Functional screening of antibiotic resistance
genes from human gut microbiota reveals
a novel gene fusion.
Cheng G, Hu Y, Yin Y, Yang X, Xiang C, Wang B, Chen Y, Yang F, Lei F, Wu N, Lu N, Li
J, Chen Q, Li L, Zhu B.
Source
Microbial Genome Research Center, CAS Key Laboratory of Pathogenic Microbiology and
Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;
Graduate University of Chinese Academy of Sciences, CAS, Beijing, China.
Abstract
The human gut microbiota has a high density of bacteria that are considered a reservoir for
antibiotic resistance genes (ARGs). In this study, one fosmid metagenomic library generated
from the gut microbiota of four healthy humans was used to screen for ARGs against seven
antibiotics. Eight new ARGs were obtained: one against amoxicillin, six against dcycloserine, and one against kanamycin. The new amoxicillin resistance gene encodes a
protein with 53% identity to a class D β-lactamase from Riemerella anatipestifer RA-GD. The
six new d-cycloserine resistance genes encode proteins with 73-81% identity to known dalanine-d-alanine ligases. The new kanamycin resistance gene encodes a protein of 274 amino
acids with an N-terminus (amino acids 1-189) that has 42% identity to the 6'-aminoglycoside
acetyltransferase [AAC(6')] from Enterococcus hirae and a C-terminus (amino acids 190-274)
with 35% identity to a hypothetical protein from Clostridiales sp. SSC/2. A functional study
on the novel kanamycin resistance gene showed that only the N-terminus conferred
kanamycin resistance. Our results showed that functional metagenomics is a useful tool for
the identification of new ARGs.
© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing
Ltd. All rights reserved.
Supplemental Content
MBio. 2012 Jun 26;3(4). pii: e00170-12. doi: 10.1128/mBio.00170-12. Print 2012.
Genomic analysis of the emergence of
vancomycin-resistant Staphylococcus
aureus.
Kobayashi SD, Musser JM, DeLeo FR.
Source
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton,
MT, USA.
Abstract
Staphylococcus aureus is a human commensal bacterium and a prominent cause of infections
globally. The high incidence of S. aureus infections is compounded by the ability of the
microbe to readily acquire resistance to antibiotics. In the United States, methicillin-resistant
S. aureus (MRSA) is a leading cause of morbidity and mortality by a single infectious agent.
Therapeutic options for severe MRSA infections are limited to a few antibiotics to which the
organism is typically susceptible, including vancomycin. Acquisition of high-level
vancomycin resistance by MRSA is a major concern, but to date, there have been only 12
vancomycin-resistant S. aureus (VRSA) isolates reported in the United States and all belong
to a phylogenetic lineage known as clonal complex 5. To gain enhanced understanding of the
genetic characteristics conducive to the acquisition of vancomycin resistance by S. aureus, V.
N. Kos et al. performed whole-genome sequencing of all 12 VRSA isolates and compared the
DNA sequences to the genomes of other S. aureus strains. The findings provide new
information about the evolutionary history of VRSA and identify genetic features that may
bear on the relationship between S. aureus clonal complex 5 strains and the acquisition of
vancomycin resistance genes from enterococci.
Supplemental Content
Infect Immun. 2009 Jul;77(7):2691-702. doi: 10.1128/IAI.01570-08. Epub 2009 May 11.
Perturbation of the small intestine
microbial ecology by streptomycin alters
pathology in a Salmonella enterica
serovar typhimurium murine model of
infection.
Garner CD, Antonopoulos DA, Wagner B, Duhamel GE, Keresztes I, Ross DA, Young VB,
Altier C.
Source
Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY
14853, USA.
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.
Supplemental Content
Trends Microbiol. 2012 Jul;20(7):313-9. doi: 10.1016/j.tim.2012.04.001. Epub 2012 May 15.
Interaction between the intestinal
microbiota and host in Clostridium
difficile colonization resistance.
Britton RA, Young VB.
Source
Department of Microbiology and Molecular Genetics, Michigan State University, East
Lansing, MI 48824, USA.
Abstract
Clostridium difficile infection (CDI) has become one of the most prevalent and costly
nosocomial infections. In spite of the importance of CDI, our knowledge of the pathogenesis
of this infection is still rudimentary. Although previous use of antibiotics is generally
considered to be the sine qua non of CDI, the mechanisms by which antibiotics render the
host susceptible to C. difficile are not well defined. In this review, we will explore what is
known about how the indigenous microbiota acts in concert with the host to prevent
colonization and virulence of C. difficile and how antibiotic administration disturbs hostmicrobiota homeostasis, leading to CDI.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Supplemental Content
Infect Immun. 2009 Jun;77(6):2367-75. doi: 10.1128/IAI.01520-08. Epub 2009 Mar 23.
Reproducible community dynamics of the
gastrointestinal microbiota following
antibiotic perturbation.
Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB.
Source
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan,
Ann Arbor, MI 48109-5623, USA.
Abstract
Shifts in microbial communities are implicated in the pathogenesis of a number of
gastrointestinal diseases, but we have limited understanding of the mechanisms that lead to
altered community structures. One difficulty with studying these mechanisms in human
subjects is the inherent baseline variability of the microbiota in different individuals. In an
effort to overcome this baseline variability, we employed a mouse model to control the host
genotype, diet, and other possible influences on the microbiota. This allowed us to determine
whether the indigenous microbiota in such mice had a stable baseline community structure
and whether this community exhibited a consistent response following antibiotic
administration. We employed a tag-sequencing strategy targeting the V6 hypervariable region
of the bacterial small-subunit (16S) rRNA combined with massively parallel sequencing to
determine the community structure of the gut microbiota. Inbred mice in a controlled
environment harbored a reproducible baseline community that was significantly impacted by
antibiotic administration. The ability of the gut microbial community to recover to baseline
following the cessation of antibiotic administration differed according to the antibiotic
regimen administered. Severe antibiotic pressure resulted in reproducible, long-lasting
alterations in the gut microbial community, including a decrease in overall diversity. The
finding of stereotypic responses of the indigenous microbiota to ecologic stress suggests that a
better understanding of the factors that govern community structure could lead to strategies
for the intentional manipulation of this ecosystem so as to preserve or restore a healthy
microbiota.
Supplemental Content
Infect Immun. 2009 Jul;77(7):2741-53. doi: 10.1128/IAI.00006-09. Epub 2009 Apr 20.
Prolonged impact of antibiotics on intestinal
microbial ecology and susceptibility to
enteric Salmonella infection.
Croswell A, Amir E, Teggatz P, Barman M, Salzman NH.
Source
Department of Pediatrics, Division of Gastroenterology, the Medical College of Wisconsin,
Milwaukee, Wisconsin 53226, USA.
Abstract
The impact of antibiotics on the host's protective microbiota and the resulting increased
susceptibility to mucosal infection are poorly understood. In this study, antibiotic regimens
commonly applied to murine enteritis models are used to examine the impact of antibiotics on
the intestinal microbiota, the time course of recovery of the biota, and the resulting
susceptibility to enteric Salmonella infection. Molecular analysis of the microbiota showed
that antibiotic treatment has an impact on the colonization of the murine gut that is site and
antibiotic dependent. While combinations of antibiotics were able to eliminate culturable
bacteria, none of the antibiotic treatments were effective at sterilizing the intestinal tract.
Recovery of total bacterial numbers occurs within 1 week after antibiotic withdrawal, but
alterations in specific bacterial groups persist for several weeks. Increased Salmonella
translocation associated with antibiotic pretreatment corrects rapidly in association with the
recovery of the most dominant bacterial group, which parallels the recovery of total bacterial
numbers. However, susceptibility to intestinal colonization and mucosal inflammation persists
when mice are infected several weeks after withdrawal of antibiotics, correlating with subtle
alterations in the intestinal microbiome involving alterations of specific bacterial groups.
These results show that the colonizing microbiotas are integral to mucosal host protection,
that specific features of the microbiome impact different aspects of enteric Salmonella
pathogenesis, and that antibiotics can have prolonged deleterious effects on intestinal
colonization resistance.
Supplemental Content
I
PLoS One. 2012;7(7):e41104. doi: 10.1371/journal.pone.0041104. Epub 2012 Jul 26.
Pharyngeal microflora disruption by
antibiotics promotes airway
hyperresponsiveness after respiratory
syncytial virus infection.
Ni K, Li S, Xia Q, Zang N, Deng Y, Xie X, Luo Z, Luo Y, Wang L, Fu Z, Liu E.
Source
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing
International Science and Technology Cooperation Center for Child Development and
Disorders, Chongqing Medical University, Chongqing, China.
Abstract
BACKGROUND:
Regulatory T cells (Treg cells), which are essential for regulation of immune response to
respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal
pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway
responsiveness and relative immune responses after RSV infection have not been clarified.
METHODS:
Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either
oral antibiotics or oral double distilled water (ddH(2)O) from 1 d post infection (pi). Changes
in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi
and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated
in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR),
pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and
TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA)
challenge was used to induce AHR after RSV infection.
RESULTS:
The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment
for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection,
AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary
Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under
OVA challenge.
CONCLUSIONS:
After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as
Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.
Supplemental Content
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G635-44.
Persistent epithelial dysfunction and
bacterial translocation after resolution of
intestinal inflammation.
Asfaha S, MacNaughton WK, Appleyard CB, Chadee K, Wallace JL.
Source
Mucosal Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary,
Alberta T2N 4N1, Canada.
Abstract
Epithelial secretion may play an important role in reducing bacterial colonization and
translocation in intestine. If so, secretory dysfunction could result in increased susceptibility
to infection and inflammation. We investigated whether long-term colonic secretory
dysfunction occurs after a bout of colitis and if this is accompanied by an increase in bacterial
colonization and translocation. Rats were studied 6 wk after induction of colitis with
trinitrobenzene sulfonic acid when inflammation had completely resolved, and epithelial
permeability was normal. Intestinal loops were stimulated with either Clostridium difficile
toxin A or a phosphodiesterase inhibitor. In vitro, colonic tissue from previously sensitized
rats was exposed to antigen (ovalbumin). Secretory responses to all three stimuli were
suppressed in rats that had previously had colitis. These rats exhibited increased (16-fold)
numbers of colonic aerobic bacteria and increased (>3-fold) bacterial translocation, similar to
results in rats studied after resolution of enteritis. Postcolitis bacterial translocation was
prevented by daily treatment with an inhibitor of inducible nitric oxide synthase. This study
demonstrates that intestinal inflammation results in prolonged impairment of colonic
epithelial secretion, which may contribute to increases in bacterial load and bacterial
translocation. Epithelial dysfunction of this type could underlie an increased propensity for
further bouts of inflammation, a hallmark of diseases such as inflammatory bowel disease.
Supplemental Content
Trends Microbiol. 2012 Jul;20(7):313-9. doi: 10.1016/j.tim.2012.04.001. Epub 2012 May 15.
Interaction between the intestinal
microbiota and host in Clostridium
difficile colonization resistance.
Britton RA, Young VB.
Source
Department of Microbiology and Molecular Genetics, Michigan State University, East
Lansing, MI 48824, USA.
Abstract
Clostridium difficile infection (CDI) has become one of the most prevalent and costly
nosocomial infections. In spite of the importance of CDI, our knowledge of the pathogenesis
of this infection is still rudimentary. Although previous use of antibiotics is generally
considered to be the sine qua non of CDI, the mechanisms by which antibiotics render the
host susceptible to C. difficile are not well defined. In this review, we will explore what is
known about how the indigenous microbiota acts in concert with the host to prevent
colonization and virulence of C. difficile and how antibiotic administration disturbs hostmicrobiota homeostasis, leading to CDI.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Supplemental Content
Trends Microbiol
Infect Immun. 1976 Jan;13(1):180-8.
Effect of penicillin on the succession,
attachment, and morphology of
segmented, filamentous microbes in the
murine small bowel.
Davis CP, Savage DC.
Abstract
Indigenous segmented filamentous microbes attach to murine ileal epithelial cells. These
microbes can be seen on the epithelial surface with a scanning electron microscope. They
colonize preferentially the distal ileum in mice. Penicillin, placed in the animal's drinking
water, eliminates the microbes from the mouse ileum, but recolinization of the ileum is
observed 4 to 5 weeks after the penicillin treatment is stopped. Within 3 to 5 h after rats are
given penicillin, the morphology of the microbes is changed. Their external surfaces are
wrinkled or broken. Vacated and partially vacated attachment sites are observed. Almost all of
the organisms disappear from murine ilea after the animals are exposed to penicillin for 10 h.
These observations are discussed in relation to the microbe itself and in its interaction with
ileal epithelial cells.
Supplemental Content
Inflamm Bowel Dis. 2012 Oct;18(10):1923-31. doi: 10.1002/ibd.22908. Epub 2012 Feb 16.
AIEC colonization and pathogenicity:
influence of previous antibiotic treatment
and preexisting inflammation.
Drouet M, Vignal C, Singer E, Djouina M, Dubreuil L, Cortot A, Desreumaux P, Neut C.
Source
University Lille Nord de France, Lille, France.
Abstract
BACKGROUND:
Inflammatory bowel diseases (IBD) patients are abnormally colonized by adherent-invasive
Escherichia coli (AIEC). NOD2 gene mutations impair intracellular bacterial clearance. We
evaluated the impact of antibiotic treatment on AIEC colonization in wildtype (WT) and
NOD2 knockout mice (NOD2KO) and the consequences on intestinal inflammation.
METHODS:
After 3 days of antibiotic treatment, mice were infected for 2 days with 10⁹ CFU AIEC and
sacrificed 1, 5, and 60 days later. In parallel, mice were challenged with AIEC subsequent to a
dextran sodium sulfate (DSS) treatment and sacrificed 9 days later. Ileum, colon, and
mesenteric tissues were sampled for AIEC quantification and evaluation of inflammation.
RESULTS:
Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice.
Compared with nontreated animals, antibiotic treatment led to a significant increase in ileal
and colonic colonization of AIEC in WT and/or NOD2KO mice. Persistent AIEC
colonization was observed until day 5 only in NOD2KO mice, disappearing at day 60.
Mesenteric translocation of AIEC was observed only in NOD2KO mice. No inflammation
was observed in WT and NOD2KO mice treated with antibiotics and infected with AIEC.
During DSS-induced colitis, colonization and persistence of AIEC was observed in the colon.
Moreover, a dramatic increase in clinical, histological, and molecular parameters of colitis
was observed in mice infected with AIEC but not with a commensal E. coli strain.
CONCLUSIONS:
Antibiotic treatment was necessary for AIEC colonization of the gut and mesenteric tissues
and persistence of AIEC was dependent on NOD2. AIEC exacerbated a preexisting DSSinduced colitis in WT mice.
Supplemental Content
J Clin Microbiol. 2004 Mar;42(3):1203-6.
Antibiotic-associated diarrhea accompanied
by large-scale alterations in the
composition of the fecal microbiota.
Young VB, Schmidt TM.
Source
Department of Microbiology and Molecular Genetics, Infectious Diseases Unit, National
Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan
48824, USA. [email protected]
Abstract
Alterations in the diversity of the gut microbiota are believed to underlie the development of
antibiotic-associated diarrhea (AAD). A molecular phylogenetic analysis was performed to
document temporal changes in the diversity of fecal bacteria of a patient who developed
AAD. Antibiotic administration was associated with distinct changes in the diversity of the
gut microbiota, including a marked decrease in the prevalence of butyrate-producing bacteria.
Following the discontinuation of the antibiotic, resolution of diarrhea was accompanied by a
reversal of these changes, providing the first direct evidence linking changes in the
community structure of the gastrointestinal bacteria with the development of AAD.
Comment in
•
Antibiotic-associated diarrhea: it's all about the butyrate. [Rev Gastroenterol Disord.
2004]
PMID:
15004076
[PubMed - indexed for MEDLINE]
Supplemental Content
Chin Med J (Engl). 2007 May 20;120(10):929-31.
Changes in the intestinal microflora of
children with Helicobacter pylori
infection and after Helicobacter pylori
eradication therapy.
Lou JG, Chen J, Huang XL, Zhao ZY.
Source
Department of Gastroenterology, Children's Hospital, Zhejiang University School of
Medicine, Hangzhou 310003, China.
Supplemental Content
Epidemiol Infect. 1989 Oct;103(2):323-32.
Investigation of the immune status of mice
during and following selective
decontamination of the digestive tract.
Speekenbrink AB, Alcock SR, Parrott DM.
Source
Department of Bacteriology and Immunology, Western Infirmary, Glasgow, Scotland, UK.
Abstract
Selective decontamination of the digestive tract (SDD) employs oral antibiotics to eliminate
aerobic Gram-negative bacilli while retaining the anaerobic flora. A combination of SDD and
parenteral cefotaxime has recently been reported to strikingly reduce the incidence of
infection in patients treated in an intensive therapy unit. The present study describes the
effects of SDD and of cefotaxime on the immune response of mice to protein antigens. The in
vivo cellular response to ovalbumin and sheep red blood cells was unchanged. However, SDD
appeared to decrease the in vitro mitogenic response of spleen cells to phytohaemagglutinin,
and cefotaxime similarly affected the response to Concanavalin A. The antibody response to
sheep red blood cells was increased in the period after discontinuation of SDD. The antibody
response was otherwise not affected. These results indicate that SDD is unlikely to have
adverse effects on the immune response to protein antigens.
Supplemental Content
Trends Microbiol. 2012 Jul;20(7):313-9. doi: 10.1016/j.tim.2012.04.001. Epub 2012 May 15.
Interaction between the intestinal
microbiota and host in Clostridium
difficile colonization resistance.
Britton RA, Young VB.
Source
Department of Microbiology and Molecular Genetics, Michigan State University, East
Lansing, MI 48824, USA.
Abstract
Clostridium difficile infection (CDI) has become one of the most prevalent and costly
nosocomial infections. In spite of the importance of CDI, our knowledge of the pathogenesis
of this infection is still rudimentary. Although previous use of antibiotics is generally
considered to be the sine qua non of CDI, the mechanisms by which antibiotics render the
host susceptible to C. difficile are not well defined. In this review, we will explore what is
known about how the indigenous microbiota acts in concert with the host to prevent
colonization and virulence of C. difficile and how antibiotic administration disturbs hostmicrobiota homeostasis, leading to CDI.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Supplemental Content
Infect Immun. 2009 Jun;77(6):2367-75. doi: 10.1128/IAI.01520-08. Epub 2009 Mar 23.
Reproducible community dynamics of the
gastrointestinal microbiota following
antibiotic perturbation.
Antonopoulos DA, Huse SM, Morrison HG, Schmidt TM, Sogin ML, Young VB.
Source
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan,
Ann Arbor, MI 48109-5623, USA.
Abstract
Shifts in microbial communities are implicated in the pathogenesis of a number of
gastrointestinal diseases, but we have limited understanding of the mechanisms that lead to
altered community structures. One difficulty with studying these mechanisms in human
subjects is the inherent baseline variability of the microbiota in different individuals. In an
effort to overcome this baseline variability, we employed a mouse model to control the host
genotype, diet, and other possible influences on the microbiota. This allowed us to determine
whether the indigenous microbiota in such mice had a stable baseline community structure
and whether this community exhibited a consistent response following antibiotic
administration. We employed a tag-sequencing strategy targeting the V6 hypervariable region
of the bacterial small-subunit (16S) rRNA combined with massively parallel sequencing to
determine the community structure of the gut microbiota. Inbred mice in a controlled
environment harbored a reproducible baseline community that was significantly impacted by
antibiotic administration. The ability of the gut microbial community to recover to baseline
following the cessation of antibiotic administration differed according to the antibiotic
regimen administered. Severe antibiotic pressure resulted in reproducible, long-lasting
alterations in the gut microbial community, including a decrease in overall diversity. The
finding of stereotypic responses of the indigenous microbiota to ecologic stress suggests that a
better understanding of the factors that govern community structure could lead to strategies
for the intentional manipulation of this ecosystem so as to preserve or restore a healthy
microbiota.
Supplemental Content
Infect Immun. 2009 Jul;77(7):2741-53. doi: 10.1128/IAI.00006-09. Epub 2009 Apr 20.
Prolonged impact of antibiotics on intestinal
microbial ecology and susceptibility to
enteric Salmonella infection.
Croswell A, Amir E, Teggatz P, Barman M, Salzman NH.
Source
Department of Pediatrics, Division of Gastroenterology, the Medical College of Wisconsin,
Milwaukee, Wisconsin 53226, USA.
Abstract
The impact of antibiotics on the host's protective microbiota and the resulting increased
susceptibility to mucosal infection are poorly understood. In this study, antibiotic regimens
commonly applied to murine enteritis models are used to examine the impact of antibiotics on
the intestinal microbiota, the time course of recovery of the biota, and the resulting
susceptibility to enteric Salmonella infection. Molecular analysis of the microbiota showed
that antibiotic treatment has an impact on the colonization of the murine gut that is site and
antibiotic dependent. While combinations of antibiotics were able to eliminate culturable
bacteria, none of the antibiotic treatments were effective at sterilizing the intestinal tract.
Recovery of total bacterial numbers occurs within 1 week after antibiotic withdrawal, but
alterations in specific bacterial groups persist for several weeks. Increased Salmonella
translocation associated with antibiotic pretreatment corrects rapidly in association with the
recovery of the most dominant bacterial group, which parallels the recovery of total bacterial
numbers. However, susceptibility to intestinal colonization and mucosal inflammation persists
when mice are infected several weeks after withdrawal of antibiotics, correlating with subtle
alterations in the intestinal microbiome involving alterations of specific bacterial groups.
These results show that the colonizing microbiotas are integral to mucosal host protection,
that specific features of the microbiome impact different aspects of enteric Salmonella
pathogenesis, and that antibiotics can have prolonged deleterious effects on intestinal
colonization resistance.
Supplemental Content