Influence of a non-probiotic bacteria on the pharmacokinetics of amiodarone (A) and N-desethylamiodarone (B).

<p>Legend Fig. 3A: Pharmacokinetics of amiodarone with or without (control group) non-probiotic <i>E. coli</i> ATCC 25922 pre-treatment. Each point is presented as means ± S.D.; N = 3. Legend Fig. 3B: Pharmacokinetics of N-desethylamiodarone (metabolite of amiodarone) with or without (control group) non-probiotic <i>E. coli</i> ATCC 25922 pre-treatment. Each point is presented as means ± S.D.; N = 3.</p

Administration of a Probiotic Can Change Drug Pharmacokinetics: Effect of <i>E. coli</i> Nissle 1917 on Amidarone Absorption in Rats

<div><p>The growing interest in the composition and effects of microbiota raised the question how drug pharmacokinetics could be influenced by concomitant application of probiotics. The aim of this study was to find whether probiotic <i>E. coli</i> strain Nissle 1917 (EcN) influences the pharmacokinetics of concomitantly taken antiarrhythmic drug amiodarone (AMI). Live bacterial suspension of probiotic EcN (or non-probiotic <i>E. coli</i> strain ATCC 25922) was applied orally to male Wistar rats for seven days, while a control group of rats was treated with a saline solution. On the eighth day, the amiodarone hydrochloride was administered as one single oral dose (50 mg/kg) to all rats (N = 60). After 0, 1, 2, 3, 4, 5.5, 7, 9, 14, 22, and 30 hours, blood samples were taken from the rat abdominal aorta. The plasma level of AMI and its metabolite N-desethylamiodarone (DEA) was determined using the HPLC with UV detection. Administration of EcN led to a 43% increase of AMI AUC_0-30 in comparison with control samples. However, this effect was not observed if EcN was replaced by a reference non-probiotic <i>E. coli</i> strain. Thus, EcN administration was most probably responsible for better drug absorption from the gastrointestinal tract. Plasma levels of DEA were also increased in plasma samples from animals treated with EcN. This change was again not found in the experiment with the reference non-probiotic strain. Higher DEA levels in samples from EcN-treated rats may be explained either by better absorption of AMI and/or by an increased activity of CYP2C forms, known to participate in metabolism of this drug, after EcN administration. In this paper, it is documented that concomitantly taken probiotic EcN may modulate pharmacokinetics of a drug; in this case, it led to an increased bioavailability of AMI.</p></div

Chromatographic profile of three compounds in biological sample: trifluoperazine (an internal), amiodarone, N-desethylamiodarone.

<p>Legend <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087150#pone-0087150-g001" target="_blank">Fig. 1</a>: i.s.: an internal standard trifluoperazine (8.32 min); amiodarone (9.31 min); N-desethylamiodarone (10.11 min). The HPLC chromatogram was obtained from the rat blood plasma sample taken 3 hours after amiodarone application.</p

Differentially produced proteins by PBMCs from all infertile patients as compared to fertile women, after their 3- or 5-day incubation with whole sperm cells.

<p>Fold change less than 1 indicates lower and more than 1 indicates higher abundance in patients with ASA as compared to fertile women. Sample size: infertile patients (n = 26); fertile women (n = 11).</p

Heat map of cytokine levels.

<p>PBMCs from patients with and without ASA produce distinct cytokine patterns after their 3- (A) and 5- (B) day cultivation with whole sperm antigen. The samples were clustered based on the similarity of their cytokine profiles into 8 clusters, using eight-way unsupervised clustering algorithm with a top down repeated bisection approach using the correlation coefficient to calculate the similarity between the protein productions. F = fertile, V = teenage virgins, P = patients without ASA, pA = patients with ASA.</p

Differentially produced proteins by PBMCs from patients with ASA as compared to patients without ASA, after their 3- or 5-day incubation with whole sperm cells.

<p>Fold change less than 1 indicates lower abundance and more than 1 indicates higher abundance in patients with ASA as compared to patients without ASA. Only significant (q<0.05) proteins are shown. FDR, false discovery rate. Sample size: patients with ASA (n = 22) and patients without ASA (n = 4).</p

The changes in cytokine production elicited by whole sperm cells or by their lysate.

<p>PBMCs from each infertile patient without serum ASA (n = 4) was incubated either with whole sperm cells or by sperm cell lysate, for either 3 or 5 days. The differences are significant as calculated by pair-matched ANOVA with Bonferroni multiple comparison test (*p<0.05, ** p<0.01, *** p<0.001). Only those cytokines, significantly different in at least one time-point are included.</p

Differentially produced proteins by PBMCs from patients with ASA as compared to fertile women, after their 3- or 5-day incubation with whole sperm cells.

<p>Fold change less than 1 indicates lower and more than 1 indicates higher abundance in patients with ASA as compared to fertile women. FDR, false discovery rate. Sample size: patients with ASA (n = 22); fertile women (n = 11).</p

MOESM1 of Development of gut inflammation in mice colonized with mucosa-associated bacteria from patients with ulcerative colitis

Additional file 1. The sequences of excised DGGE bands

A germ-free postnatal period affects long-term immune-regulatory homeostasis.

<p>Percentages of regulatory T cells (CD4⁺FoxP3⁺) and tolerogenic dendritic cells (CD103⁺CD11c⁺) in cells isolated from spleen (SPL) and mesenteric lymph node (MLN) were determined by flow cytometry. Specific Pathogen Free mice (SPF), germ-free mice (GF) and ex-GF mice inoculated with a caecal microbiota suspension or co-housed with SPF mice at one (1W) or three weeks (3W) of age are illustrated. Error bars represent the SEM. * represents <i>p</i><0.05, ** <0.01, *** <0.001 compared with SPF mice.</p