scholarly journals Impact of Kefir DerivedLactobacillus kefirion the Mucosal Immune Response and Gut Microbiota

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
P. Carasi ◽  
S. M. Racedo ◽  
C. Jacquot ◽  
D. E. Romanin ◽  
M. A. Serradell ◽  
...  
Keyword(s):  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Pcr Analysis ◽  
Mesenteric Lymph Nodes ◽  
Reporter System ◽  
Gm Csf ◽  
Proinflammatory Mediators ◽  
Probiotic Treatment ◽  
The Impact

The evaluation of the impact of probiotics on host health could help to understand how they can be used in the prevention of diseases. On the basis of our previous studies andin vitroassays on PBMC and Caco-2 ccl20:luc reporter system presented in this work, the strainLactobacillus kefiriCIDCA 8348 was selected and administrated to healthy Swiss mice daily for 21 days. The probiotic treatment increased IgA in feces and reduced expression of proinflammatory mediators in Peyer Patches and mesenteric lymph nodes, where it also increased IL-10. In ileum IL-10, CXCL-1 and mucin 6 genes were upregulated; meanwhile in colon mucin 4 was induced whereas IFN-γ, GM-CSF, and IL-1βgenes were downregulated. Moreover, ileum and colon explants showed the anti-inflammatory effect ofL. kefirisince the LPS-induced increment of IL-6 and GM-CSF levels in control mice was significantly attenuated inL. kefiritreated mice. Regarding fecal microbiota, DGGE profiles allowed differentiation of experimental groups in two separated clusters. Quantitative PCR analysis of different bacterial groups revealed only significant changes inLactobacilluspopulation. In conclusion,L. kefiriis a good candidate to be used in gut inflammatory disorders.

scholarly journals Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Sukumaran ◽  
S. Pladwig ◽  
J. Geddes-McAlister
Keyword(s):  
Klebsiella Pneumoniae ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Cellular Protein ◽  
Pcr Analysis ◽  
Phenotypic Analysis ◽  
Metal Ion Homeostasis ◽  
Capsule Production ◽  
The Impact

Abstract Background Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host. Results Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain. Conclusions This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.

Phase II Window Study of the Farnesyltransferase Inhibitor R115777 (Zarnestra®) in Untreated Juvenile Myelomonocytic Leukemia (JMML): A Children’s Oncology Group Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2587-2587 ◽  
Author(s):  
Robert P. Castleberry ◽  
Mignon L. Loh ◽  
Nalini Jayaprakash ◽  
April Peterson ◽  
Vicky Casey ◽  
...  
Keyword(s):  
Phase Ii ◽  
Initial Dosage ◽  
Colony Growth ◽  
Juvenile Myelomonocytic Leukemia ◽  
Cell Transplant ◽  
Monocyte Count ◽  
Similar Frequency ◽  
Gm Csf ◽  
The Impact

Abstract JMML is a rare and often fatal leukemia of young children exhibiting unique clinical, hematopoietic and genetic features including GM-CSF hypersensitivity, and mutations of NF1, RAS, and PTPN11. Ras proteins control a number of cell signaling events becoming activated in part by the addition of a farnesyl moiety via farnesyl protein transferase (FTPase). Given that hyperactive Ras is central to JMML pathogenesis, it is intuitive that an FTPase is an appropriate therapeutic target in JMML. One FTPase inhibitor, L739,749, has previously been shown to abrogate spontaneous in vitro colony growth in 9 JMML samples (Blood 95:639, 2000). R115777 is a potent in vitro and in vivo inhibitor of FTPase, abrogating the growth of H-ras, K-ras and N-ras transformed tumors. In humans, it is well tolerated with the dose-limiting toxicities being myelosuppression and diarrhea. To assess the efficacy and toxicity of R115777 in JMML, a phase II window study was conducted as a part of COG study AAML0122 in newly diagnosed patients who were given the option of receiving this agent prior to cytosine arabinoside, fludarabine and 13-cis retinoic acid followed by stem cell transplant. R115777 was administered PO BID for 21 days with a 7 day rest for two courses in the absence of disease progression or excessive toxicity. The starting dosage in the first 11 patients was 200mg/m2 with escalation in subsequent patients to 300mg/m2 if the initial dosage was tolerated. Overall response was based upon changes in WBC and organomegaly. The impact of R115777 upon in vitro spontaneous colony growth, GM-CSF hypersensitivity and farnesylation was monitored. A total of 47 patients were accrued: M:F=30:17, median (med) age 15 mos. (1–76); med WBC 30X109/L (4–151); med monocyte count 18X109/L (1–55); med platelet count 58X109/L (2–587); elevated fetal hemoglobin 30 (65%). RAS and PTPN11 mutations were tested in 42 cases and inhibition of prenylation in 33. R115777 was well tolerated at both dosages with the most common grade 3/4 toxicities being thrombocytopenia (40%), anemia (40%), neutropenia (15%), and diarrhea (6%). There were no deaths during the trial. The table details the responses in patients receiving one course (N=47) and 2 courses (N=38) of R115777. The 9 patients not receiving two courses were removed from study due to lack of response or progressive disease. WBC ONLY 0VERALL (WBC & organomegaly) COURSE #1 CR CR PR MR SD PD Total     200mg/m2 6 0 4 4 2 1 11     300mg/m2 18 1 17 9 4 5 36 COURSE #2     200mg/m2 6 0 6 1 2 1 10     300mg/m2 17 2 14 7 2 3 28 FTPase activity was inhibited in 13/15 cases (med 71%; range 38–91%) with similar frequency and degree of inhibition at both dosages of R115777. There was no relationship between FTPase inhibition or response and the presence of RAS/PTPN11 mutations or inhibition of prenylation in an HJ2 assay. In conclusion, R115777 provides an overall CR/PR rate of 58% with no significant differences between the two dosages (p=0.7). This agent should be considered in the future management of JMML.

scholarly journals An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Ponce-Alonso ◽  
Carlota García-Hoz ◽  
Ana Halperin ◽  
Javier Nuño ◽  
Pilar Nicolás ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Clinical Success ◽  
Immunological Response ◽  
Organ Donor ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Donor Selection ◽  
Selection For

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

scholarly journals Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Ming Xu ◽  
Hong-Li Huang ◽  
Jing Xu ◽  
Jie He ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Butyric Acid ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
16S Sequencing ◽  
Α Diversity ◽  
The Impact

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

scholarly journals Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Julyanne Brassard ◽  
Joanny Roy ◽  
Anne-Marie Lemay ◽  
Marie-Josée Beaulieu ◽  
Emilie Bernatchez ◽  
...  
Keyword(s):  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Intracellular Localization ◽  
Receptor Internalization ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gm Csf ◽  
Dendritic Cell Population ◽  
The Impact

Lung dendritic cells (DCs) are divided into two major populations, which include CD103+XCR1+ cDC1s and CD11b+Sirpα+ cDC2s. The maintenance of their relative proportions is dynamic and lung inflammation, such as caused by exposure to lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, can have a significant impact on the local cDC signature. Alterations in the lung cDC signature could modify the capacity of the immune system to respond to various pathogens. We consequently aimed to assess the impact of the Gram-negative bacteria Pseudomonas aeruginosa on lung cDC1 and cDC2 populations, and to identify the mechanisms leading to alterations in cDC populations. We observed that exposure to P. aeruginosa decreased the proportions of CD103+XCR1+ cDC1s, while increasing that of CD11b+ DCs. We identified two potential mechanisms involved in this modulation of lung cDC populations. First, we observed an increase in bone marrow pre-DC IRF4 expression suggesting a higher propensity of pre-DCs to differentiate towards the cDC2 lineage. This observation was combined with a reduced capacity of lung XCR1+ DC1s to express CD103. In vitro, we demonstrated that GM-CSF-induced CD103 expression on cDCs depends on GM-CSF receptor internalization and RUNX1 activity. Furthermore, we observed that cDCs stimulation with LPS or P. aeruginosa reduced the proportions of intracellular GM-CSF receptor and decreased RUNX1 mRNA expression. Altogether, these results suggest that alterations in GM-CSF receptor intracellular localization and RUNX1 signaling could be involved in the reduced CD103 expression on cDC1 in response to P. aeruginosa. To verify whether the capacity of cDCs to express CD103 following P. aeruginosa exposure impacts the immune response, WT and Cd103-/- mice were exposed to P. aeruginosa. Lack of CD103 expression led to an increase in the number of neutrophils in the airways, suggesting that lack of CD103 expression on cDC1s could favor the innate immune response to this bacterium.

Trastuzumab versus MYL-1401O (a proposed trastuzumab biosimilar) in a phase I bioequivalence study: In vivo and in vitro immunomodulation.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 10-10
Author(s):  
Régine Audran ◽  
Haithem Chtioui ◽  
Anne-Christine Thierry ◽  
Carole Mayor ◽  
Laure Vallotton ◽  
...  
Keyword(s):  
Phase I ◽  
Mononuclear Cell ◽  
Ex Vivo ◽  
Reference Drug ◽  
Gm Csf ◽  
Significant Difference ◽  
Ifn Γ ◽  
The Impact

10 Background: Trastuzumab is a humanized monoclonal antibody targeting breast cancer cells overexpressing the HER2-oncoprotein. During a Phase-I single centre, single dose, randomized, double-blind, cross-over study assessing the bioequivalence of a proposed trastuzumab biosimilar (MYL-1401O) versus the initially marketed drug (Herceptin), we investigated in addition a large panel of pharmacodynamics parameters comparing the immunomodulatory activity of both drugs. Methods: 22 healthy males were included, 19 subjects receiving randomly a single intravenous infusion of MYL-1401O and 22 of Herceptin, separated by 16 to 22 week wash-out. Blood samples drawn pre- and post- infusion were assessed for in vivo serum cytokines induction (IL-1β, IL-2, IL-6, IL-10, IL-12, TNF-α, GM-CSF and IFN-γ) whereas the impact of treatment on mononuclear cell subsets and their level of activation was tested ex vivo. Volunteers’ PBMC (peripheral blood monocnuclear cells) were stimulated in vitro with recall antigens and mitogen for cytokine production. At baseline, we performed in addition a cytokine release assay on PBMC upon stimulation with trastuzumab as a preclinical safety test. Results: Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6h, and a modulation of mononuclear cell subset profile and level of activation. Notably CD16+ cells frequency decreased at 3h and peaked at 48h. Except for CD8+ T cells, there were no significant differences between Herceptin and its proposed biosimilar ex vivo. PBMC stimulated in vitro with trastuzumab secreted IL-6, TNF-a, IL-1β, GM-CSF, IFN-γ, and IL-10, but no IL-2. There was no significant difference between the two mAbs. Conclusions: Based on these in vivo, ex vivo and in vitro experiments, there is a strong assumption that MYL-1401O is biosimilar to the reference drug Herceptin for its immunomodulation properties as already proven for its bioequivalence. Clinical trial information: 2011-001406-94.

scholarly journals Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1α–initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine–Chemokine Axis

1999 ◽  
Vol 189 (12) ◽  
pp. 1923-1930 ◽  
Author(s):  
Mohamed Hachicha ◽  
Marc Pouliot ◽  
Nicos A. Petasis ◽  
Charles N. Serhan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gm Csf ◽  
Tnf Α ◽  
Human Polymorphonuclear Leukocytes ◽  
The Impact ◽  
Receptor Antibodies ◽  
Necrosis Factor

The impact of  lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-α–initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1–10 nM, the LXA4 and ATL analogues each inhibited TNF-α–stimulated superoxide anion generation and IL-1β release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-α, as these responses were not altered with either GM-CSF– or zymosan-stimulated cells. TNF-α–induced IL-1β gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-α–stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1β, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-α–directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

The Susceptibility to X4 and R5 Human Immunodeficiency Virus-1 Strains of Dendritic Cells Derived In Vitro From CD34+ Hematopoietic Progenitor Cells Is Primarily Determined by Their Maturation Stage

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3866-3875 ◽  
Author(s):  
Bruno Canque ◽  
Youssef Bakri ◽  
Sandrine Camus ◽  
Micael Yagello ◽  
Abdelaziz Benjouad ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Virus Production ◽  
Cd40 Ligand ◽  
Interleukin 4 ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Gm Csf ◽  
Immunodeficiency Virus

Dendritic cells (DC) were sorted on day 8 from cultures of CD34+ cells with stem cell factor/Flt-3 ligand/ granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor- (TNF-)/interleukin-4 (IL-4). Exposing immature CCR5+CXCR4lo/− DC to CCR5-dependent human immunodeficiency virus (HIV)-1Ba-L led to productive and cytopathic infection, whereas only low virus production occurred in CXCR4-dependent HIV-1LAI–exposed DC. PCR analysis of the DC 48 hours postinfection showed efficient entry of HIV-1Ba-L but not of HIV-1LAI. CD40 ligand- or monocyte-conditioned medium-induced maturation of HIV-1Ba-L–infected DC reduced virus production by about 1 Log, while cells became CCR5−. However, HIV-1Ba-L–exposed mature DC harbored 15-fold more viral DNA than their immature counterparts, ruling out inhibition of virus entry. Simultaneously, CXCR4 upregulation by mature DC coincided with highly efficient entry of HIV-1LAI which, nonetheless, replicated at the same low level in mature as in immature DC. In line with these findings, coculture of HIV-1Ba-L–infected immature DC with CD3 monoclonal antibody–activated autologous CD4+ T lymphocytes in the presence of AZT decreased virus production by the DC. Finally, whether they originated from CD1a+CD14− or CD1a−CD14+ precursors, DC did not differ as regards permissivity to HIV, although CD1a+CD14− precursor-derived immature DC could produce higher HIV-1Ba-L amounts than their CD1a−CD14+ counterparts. Thus, both DC permissivity to, and capacity to support replication of, HIV is primarily determined by their maturation stage.

The Susceptibility to X4 and R5 Human Immunodeficiency Virus-1 Strains of Dendritic Cells Derived In Vitro From CD34+ Hematopoietic Progenitor Cells Is Primarily Determined by Their Maturation Stage

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3866-3875 ◽  
Author(s):  
Bruno Canque ◽  
Youssef Bakri ◽  
Sandrine Camus ◽  
Micael Yagello ◽  
Abdelaziz Benjouad ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Virus Production ◽  
Cd40 Ligand ◽  
Interleukin 4 ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Gm Csf ◽  
Immunodeficiency Virus

Abstract Dendritic cells (DC) were sorted on day 8 from cultures of CD34+ cells with stem cell factor/Flt-3 ligand/ granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor- (TNF-)/interleukin-4 (IL-4). Exposing immature CCR5+CXCR4lo/− DC to CCR5-dependent human immunodeficiency virus (HIV)-1Ba-L led to productive and cytopathic infection, whereas only low virus production occurred in CXCR4-dependent HIV-1LAI–exposed DC. PCR analysis of the DC 48 hours postinfection showed efficient entry of HIV-1Ba-L but not of HIV-1LAI. CD40 ligand- or monocyte-conditioned medium-induced maturation of HIV-1Ba-L–infected DC reduced virus production by about 1 Log, while cells became CCR5−. However, HIV-1Ba-L–exposed mature DC harbored 15-fold more viral DNA than their immature counterparts, ruling out inhibition of virus entry. Simultaneously, CXCR4 upregulation by mature DC coincided with highly efficient entry of HIV-1LAI which, nonetheless, replicated at the same low level in mature as in immature DC. In line with these findings, coculture of HIV-1Ba-L–infected immature DC with CD3 monoclonal antibody–activated autologous CD4+ T lymphocytes in the presence of AZT decreased virus production by the DC. Finally, whether they originated from CD1a+CD14− or CD1a−CD14+ precursors, DC did not differ as regards permissivity to HIV, although CD1a+CD14− precursor-derived immature DC could produce higher HIV-1Ba-L amounts than their CD1a−CD14+ counterparts. Thus, both DC permissivity to, and capacity to support replication of, HIV is primarily determined by their maturation stage.

scholarly journals Escherichia coli Probiotic Strain ED1a in Pigs Has a Limited Impact on the Gut Carriage of Extended-Spectrum-β-Lactamase-Producing E. coli

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
G. Mourand ◽  
F. Paboeuf ◽  
M. A. Fleury ◽  
E. Jouy ◽  
S. Bougeard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Probiotic Strain ◽  
Fecal Excretion ◽  
Experimental Conditions ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum ◽  
Probiotic Treatment ◽  
The Impact

ABSTRACT Four trials were conducted to evaluate the impact of Escherichia coli probiotic strain ED1a administration to pigs on the gut carriage or survival in manure of extended-spectrum-β-lactamase-producing E. coli. Groups of pigs were orally inoculated with strain E. coli M63 carrying the bla CTX-M-1 gene (n = 84) or used as a control (n = 26). In the first two trials, 24 of 40 E. coli M63-inoculated pigs were given E. coli ED1a orally for 6 days starting 8 days after oral inoculation. In the third trial, 10 E. coli M63-inoculated pigs were given either E. coli ED1a or probiotic E. coli Nissle 1917 for 5 days. In the fourth trial, E. coli ED1a was given to a sow and its 12 piglets, and these 12 piglets plus 12 piglets that had not received E. coli ED1a were then inoculated with E. coli M63. Fecal shedding of cefotaxime-resistant Enterobacteriaceae (CTX-RE) was studied by culture, and bla CTX-M-1 genes were quantified by PCR. The persistence of CTX-RE in manure samples from inoculated pigs or manure samples inoculated in vitro with E. coli M63 with or without probiotics was studied. The results showed that E. coli M63 and ED1a were good gut colonizers. The reduction in the level of fecal excretion of CTX-RE in E. coli ED1a-treated pigs compared to that in nontreated pigs was usually less than 1 log10 CFU and was mainly observed during the probiotic administration period. The results obtained with E. coli Nissle 1917 did not differ significantly from those obtained with E. coli ED1a. CTX-RE survival did not differ significantly in manure samples with or without probiotic treatment. In conclusion, under our experimental conditions, E. coli ED1a and E. coli Nissle 1917 could not durably prevent CTX-RE colonization of the pig gut.

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