Dataset Information

A prospective, randomized, blinded, placebo-controlled pilot study on the effect of Enterococcus faecium on clinical activity and intestinal gene expression in canine food-responsive chronic enteropathy.

ABSTRACT:

Background

Canine chronic enteropathies (CE) are believed to be caused by an aberrant immune response towards the intestinal microbiome. Administration of probiotics can alleviate colitis in people. In vitro effects of the probiotic Enterococcus faecium NCIMB 10415 E1707 (EF) previously have been evaluated using canine cells (e.g., whole blood, intestinal biopsies), but data on in vivo efficacy are lacking.

Hypothesis/objectives

Administration of EF to dogs with food-responsive CE will improve clinical outcome and decrease the intestinal inflammatory profile.

Animals

Dogs diagnosed with CE were prospectively recruited to receive a hydrolyzed elimination diet plus either a synbiotic product containing EF or placebo for 6 weeks. Both veterinary staff and owners were blinded to the treatment.

Methods

Clinical severity index (CCECAI), clinicopathological data and gene expression using intestinal biopsies (TLR2/4/5/9, IL-17A, IL-22, IL-23p19, RORC, IL-2, IL-12p35, TNF?, IL-4, IFNy, IL-10, TGF?, IL-1?, IL-18, NLRP3, casp-1, TFF1, TFF3 and PPARy) before and after 6 weeks of treatment were analyzed using linear mixed modeling.

Results

Of the 45 cases recruited, 12 finished the clinical trial. Seven received the synbiotic and 5 the placebo product. There was no difference between groups or treatments regarding clinical efficacy, histology scores or expression of any of the investigated genes.

Conclusions and clinical importance

Standard dietary treatment induced rapid clinical response in all cases. Because the study was underpowered, it was not possible to determine whether or not EF had an additional effect within the time period of 6 weeks.

SUBMITTER: Schmitz S

PROVIDER: S-EPMC4895498 | biostudies-literature | 2015 Mar-Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A prospective, randomized, blinded, placebo-controlled pilot study on the effect of Enterococcus faecium on clinical activity and intestinal gene expression in canine food-responsive chronic enteropathy.

Schmitz S S Glanemann B B Garden O A OA Brooks H H Chang Y M YM Werling D D Allenspach K K

Journal of veterinary internal medicine 20150316 2

<h4>Background</h4>Canine chronic enteropathies (CE) are believed to be caused by an aberrant immune response towards the intestinal microbiome. Administration of probiotics can alleviate colitis in people. In vitro effects of the probiotic Enterococcus faecium NCIMB 10415 E1707 (EF) previously have been evaluated using canine cells (e.g., whole blood, intestinal biopsies), but data on in vivo efficacy are lacking.<h4>Hypothesis/objectives</h4>Administration of EF to dogs with food-responsive CE ...[more]

PMID: 25776251

Similar Datasets

Project description:Background: Canine chronic enteropathies (CE) are a group of intestinal diseases that can be categorized based on treatment response into diet- or food- responsive enteropathy (FRD), antibiotic-responsive enteropathy, steroid-responsive enteropathy, and non-responsive enteropathy. CE can often be associated with intestinal dysbiosis and thus administration of probiotic or synbiotic products may provide a useful tool for the management of some of these patients. Enterococcus faecium (EF) is a probiotic strain included in a commercially available synbiotic for small animals, however its impact on the microbial communities in dogs with FRD has not yet been evaluated. Hypothesis/Objectives: The administration of a synbiotic will lead to a significant difference of the fecal microbial composition and/or diversity in dogs with FRD, and these changes are not attributable to diet change alone. Animals/Samples: Twelve dogs with FRD fed a hydrolyzed protein diet received either a synbiotic (EF, fructooligosaccharides, gum Arabic) or placebo. Fecal samples were taken before and 6 weeks into treatment. Fecal samples were also acquired from 8 healthy dogs before and 6 weeks after being switched to the same hydrolyzed protein diet as their sole food. Methods: Bacterial DNA was extracted from fecal samples and next generation sequencing based on the 16S rRNA genes was performed. Microbial composition and diversity between groups were compared using QIIME. Results: There was a small increase in species diversity in the feces of dogs with FRD treated with synbiotics. However, there were no significant differences in microbial community composition before and after 6 weeks in either the synbiotic or placebo treated dogs with FRD or the healthy dogs. In all groups, large individual variations were observed. Conclusions: No changes in microbial composition were observed in diseased or healthy dogs with diet change alone. However, administration of a synbiotic increased bacterial richness in both groups.

Project description:Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.

Project description:Enterococci are among the leading causes of hospital-acquired infections in the United States and Europe, with Enterococcus faecalis and Enterococcus faecium being the two most common species isolated from enterococcal infections. In the last decade, the proportion of enterococcal infections caused by E. faecium has steadily increased compared to other Enterococcus species. Although the underlying mechanism for the gradual replacement of E. faecalis by E. faecium in the hospital environment is not yet understood, many studies using genotyping and phylogenetic analysis have shown the emergence of a globally dispersed polyclonal subcluster of E. faecium strains in clinical environments. Systematic study of the molecular epidemiology and pathogenesis of E. faecium has been hindered by the lack of closed, complete E. faecium genomes that can be used as references.In this study, we report the complete genome sequence of the E. faecium strain TX16, also known as DO, which belongs to multilocus sequence type (ST) 18, and was the first E. faecium strain ever sequenced. Whole genome comparison of the TX16 genome with 21 E. faecium draft genomes confirmed that most clinical, outbreak, and hospital-associated (HA) strains (including STs 16, 17, 18, and 78), in addition to strains of non-hospital origin, group in the same clade (referred to as the HA clade) and are evolutionally considerably more closely related to each other by phylogenetic and gene content similarity analyses than to isolates in the community-associated (CA) clade with approximately a 3-4% average nucleotide sequence difference between the two clades at the core genome level. Our study also revealed that many genomic loci in the TX16 genome are unique to the HA clade. 380 ORFs in TX16 are HA-clade specific and antibiotic resistance genes are enriched in HA-clade strains. Mobile elements such as IS16 and transposons were also found almost exclusively in HA strains, as previously reported.Our findings along with other studies show that HA clonal lineages harbor specific genetic elements as well as sequence differences in the core genome which may confer selection advantages over the more heterogeneous CA E. faecium isolates. Which of these differences are important for the success of specific E. faecium lineages in the hospital environment remain(s) to be determined.

Project description:Enterococcus faecium has become a major opportunistic pathogen with the emergence of multidrug-resistant clones that are well-adapted to the hospital environment. As part of the vast diversity of gut microbiota, they are faced with different environmental stress, including antimicrobial pressure. By contrast, little is known about the effect of non-antibiotic molecules on bacterial physiology while numerous drugs are used in inpatients, especially those hospitalized in intensive care units (ICUs). The aim of this study was to investigate the impact of the most prescribed xenobiotics in ICUs on fitness, pathogenicity and antimicrobial resistance of E. faecium. Several phenotypic analysis was carried out and we rapidly brought to light that caspofungin, an antifungal agent belonging to the echinocandin family, seemed to have an important impact on E. faecium growth. Since the fungal target of caspofungin [beta-(1,3)-glucan synthase] is absent in enterococci, the mechanism of caspofungin action was investigated by several approaches. First, we decided to confirm this result by electronic microscopy and a peptidoglycan analysis by Ultra Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS/MS). Again, we highlighted that caspofungin even at subinhibitory concentrations (SICs) seemed to have an impact on cell wall organization especially in muropeptide precursors abundance. Then, a transcriptomic analysis was performed by RNA-seq (HiSeq 2500, Illumina) using the vanB-positive reference strain E. faecium Aus0004 in the presence or absence of caspofungin SIC (8 mg/L i.e., ¼ of the MIC). Transcriptomic analysis showed that the expression of 568 genes (19.9% of the genome) was significantly altered in the presence of caspofungin SIC, with 323 genes induced (fold change >2, p-value <0.1) and 245 genes repressed (fold change <-2, p-value <0.1). Regarding the repressed genes, the pdhABCD operon is largely downregulated (fold changes -4.3, -9.7, -6.9 and -6.4, respectively). This operon encoded components of the pyruvate deshydrogenase multienzyme complex involved in bacterial energetic pathway by the citrate cycle (i.e., TCA cycle). Moreover, it seemed that the glycerol metabolism pathway and in particular the glpOKF operon is downregulated too. The dramatic alteration of TCA seemed to have an drastic impact on bacterial cells viability indeed decrease of glycerol metabolism could explain the conformational modifications of peptidoglycan.

Dataset Information

A prospective, randomized, blinded, placebo-controlled pilot study on the effect of Enterococcus faecium on clinical activity and intestinal gene expression in canine food-responsive chronic enteropathy.

Background

Hypothesis/objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

A prospective, randomized, blinded, placebo-controlled pilot study on the effect of Enterococcus faecium on clinical activity and intestinal gene expression in canine food-responsive chronic enteropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets