Dataset Information

The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

ABSTRACT: Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCR?(-/-)?(-/-), J(H) (-/-), IgA(-/-), pIgR(-/-)). Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using 'L-mice' which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear S. tm(att) from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance (?=?pathogen blockage by an intact microbiota), the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most "classical" immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has implications for curing S. typhimurium diarrhea and for preventing transmission.

SUBMITTER: Endt K

PROVIDER: S-EPMC2936549 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

Endt Kathrin K Stecher Bärbel B Chaffron Samuel S Slack Emma E Tchitchek Nicolas N Benecke Arndt A Van Maele Laurye L Sirard Jean-Claude JC Mueller Andreas J AJ Heikenwalder Mathias M Macpherson Andrew J AJ Strugnell Richard R von Mering Christian C Hardt Wolf-Dietrich WD

PLoS pathogens 20100909 9

Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed ...[more]

PMID: 20844578

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Project description:BackgroundNon-typhoidal Salmonella (NTS) commonly causes diarrhoea, and is usually self-limiting, although sometimes people become ill with sepsis and dehydration. Routine antibiotic use for this infection could result in persistent colonization and the spread of resistant bacterial strains.ObjectivesTo assess the efficacy and safety of giving antibiotics to people with NTS diarrhoea.Search methodsWe searched the Cochrane Infectious Diseases Group trials register (up to August 2012), the Cochrane Controlled Trials Register (CENTRAL) published in The Cochrane Library (up to Issue 8 2012); and MEDLINE, African Index Medicus, CINAHL, EMBASE, LILACS, and the Science Citation Index, all up to 6 August 2012. We also searched the metaRegister of Controlled Trials (mRCT) for both completed and on going trials and reference lists of relevant articles.Selection criteriaRandomized controlled trials (RCTs) comparing any antibiotic treatment for diarrhoea caused by NTS species with placebo or no antibiotic treatment. We selected trials that included people of all ages who were symptomatic for NTS infection. Examples of symptoms included fever, abdominal pain, vomiting and diarrhoea. We excluded trials where the outcomes were not reported separately for the NTS subgroup of patients. Two review authors independently applied eligibility criteria prior to study inclusion.Data collection and analysisTwo review authors independently extracted data on pre-specified outcomes and independently assessed the risk of bias of included studies. The primary outcome was the presence of diarrhoea between two to four days after treatment. The quality of evidence was assessed using the GRADE methods.Main resultsTwelve trials involving 767 participants were included. No differences were detected between the antibiotic and placebo/no treatment arms for people with diarrhoea at two to four days after treatment (risk ratio (RR) 1.75, 95% confidence interval (CI) 0.42 to 7.21; one trial, 46 participants; very low quality evidence). No difference was detected for the presence of diarrhoea at five to seven days after treatment (RR 0.83, 95% CI 0.62 to 1.12; two trials, 192 participants; very low quality evidence), clinical failure (RR 0.88, 95% CI 0.62 to 1.25; seven trials, 440 participants; very low quality evidence). The mean difference for diarrhoea was 0 days (95% CI -0.54 to 0.54; 202 participants, four studies; low quality evidence);for fever was 0.27 days (95% CI -0.11 to 0.65; 107 participants, two studies; very low quality evidence); and for duration of illness was 0 days (95% CI -0.68 to 0.68; 116 participants, two studies; very low quality evidence). Quinolone antibiotic treatment resulted in a significantly higher number of negative stool cultures for NTS during the first week of treatment (microbiological failure: RR 0.33, 95% CI 0.20 to 0.56; 166 participants, four trials).Antibiotic treatment meant passage of the same Salmonella serovar one month after treatment was almost twice as likely (RR 1.96, 95% CI 1.29 to 2.98; 112 participants, three trials), which was statistically significant. Non-severe adverse drug reactions were more common among the patients who received antibiotic treatment.Authors' conclusionsThere is no evidence of benefit for antibiotics in NTS diarrhoea in otherwise healthy people. We are uncertain of the effects in very young people, very old people, and in people with severe and extraintestinal disease. A slightly higher number of adverse events were noted in people who received antibiotic treatment for NTS.

Dataset Information

The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

Publications

The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

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