FK-23 Preparation Research Articles

A double-blind, placebo-controlled evaluation of orally administered heat-killed Enterococcus faecalis FK-23 preparation in atopic dogs.

Gastrointestinal microbiome modulation is reported to be an effective therapy to reduce the clinical signs of canine atopic dermatitis (cAD). The killed strain of Enterococcus faecalis FK-23 has been shown to reduce allergic responses in mice and people. The aim of this multicentre, double-blinded, placebo-controlled study was to evaluate the safety and efficacy of an orally administered heat-killed E.faecalis FK-23 preparation (FK-23p) for the control of cAD. Thirty-nine client-owned dogs with clinical signs of nonseasonal cAD were enrolled by 10 veterinarians at 15 hospitals. Dogs were randomized to either FK-23p at a dose of ≥100mg/kg/day or placebo. Owner-assessed pruritus Visual Analog Scale (pVAS), clinician-assessed Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-4) and daily medication scoring (DMS) were evaluated on days 0, 28, 56 and 84. Owners and clinicians were interviewed about the overall response to treatment (RTT), after the study. The CADESI-4 significantly decreased in the FK-23p group compared to the placebo group, by Day 84 (P=0.035; Wilcoxon-Mann-Whitney U-test). There was no significant difference in pVAS and DMS between the groups. Owners and clinicians reported significantly better RTT in the FK-23p group than the placebo group (P=0.043 and 0.002, respectively; Wilcoxon-Mann-Whitney U-test). There were no adverse events associated with FK-23p. Oral administration of FK-23p provided a small, but measurable benefit when used as an adjunct treatment, in reducing clinical signs of atopic dogs.

Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C virus infection.

A clinical trial was conducted on 39 adult HCV-positive subjects to determine the safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the selection criteria and gave voluntary consent were recruited from attendees of the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar). Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples were taken at enrollment and every 3 months and tested for alanine aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total protein, hemoglobin and platelet count were determined every 6 months. Among the subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT levels were observed at 3 months (34. 9 ± 15.1 IU/l) as compared with the initial level (64.8 ± 17.5 IU/l) and persisted up to 36 months (43.7 ± 25.2 IU/l). Decrease of AST was detected after 9 months (46.2 ± 21.7 IU/l) of probiotic therapy as compared with the initial level (64.3 ± 28.7 IU/l). FK-23 was safe based on the stable levels of biochemical and hematological parameters and the absence of untoward side effects. The FK-23 preparation was well tolerated and accepted by the subjects.

Application of Enterococcus Faecalis FK-23 in Fattening of the Japanese Black Cattle

Objective: By investigating the effects of feeding Enterococcus faecalis FK-23 preparation to Japanese Black cattle inthe late fattening period, this paper discusses the increased value of beef and the feasibility. Method: 10 beef cattle weregrouped into the Test Group and the Control Group, 5 beef cattle in the Test Group were fed E. faecalis FK-23preparation at 8.0 g per day per head. The experiment included weight measure, blood test for White Blood Cell (WBC),Vitamin A (VA), Vitamin E (VE), Total Cholesterol (TC), glutamic oxaloacetic transaminase (GOT), blood ureanitrogen (BUN) and blood glucose (GLU), and HPLC test for fatty acid composition in neutral fat. Results: Comparingto the Control Group, the Test Group had excessive appetite, appreciable increase of daily gain (DG) (p

Evaluation of Risk and Benefit of Oral Immunomodulation using Heat-killed Enterococcus Faecalis FK-23 Preparation in Healthy Dogs

The risk and benefit of oral immunomodulation using heat-killed Enterococcus faecalis FK-23 preparation (FK-23) were evaluated in healthy dogs. Dogs were administered perorally 100 mg/kg of FK23 daily for 3 months. FK-23 did not affect the findings of complete blood count, leukocyte differential count, blood chemistry, serum electrolyte, radiography, or physical conditions of the dogs tested. Increase in myeloid/erythroid ratio and granulocytic lineage was found in bone marrow of the FK-23 treated dogs. Neutrophil function assessed by zymosan-dependent chemiluminescence was activated by treatment of the drug. FK-23 also stimulated in vitro lymphocyte blast transformation of PHA, Con A, and LPS. FK-23 thus appears to be a useful immunomodulating drug to stimulate non-specific host immune responses without adverse side effects.

Single administration of enterococcal preparation (FK-23) augments non-specific immune responses in healthy dogs

Influence of a single administration of heat-killed Enterococcus faecalis FK-23 preparation (FK-23) on non-specific immune responses was evaluated in healthy dogs. The dogs received a single administration of FK-23 at a dose of 100 mg/kg perorally and thereafter a complete blood count (CBC) , leukocyte differential count, phagocytic activity of peripheral blood neutrophils and a lymphocyte blast transformation (LBT) test were assessed. Although FK-23 had no effect on the CBC or leukocyte differential count, treatment of the drug caused a 1.4-fold increase in neutrophil phagocytosis compared to FK-23 non-treated healthy dogs. LBT activities of phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were also activated to twice the control levels and that of concanavalin A (Con A) was increased to one and a half times by the FK-23 treatment. Thus, a single administration of FK-23 appears to augment host resistance through stimulation of the non-specific immune responses in vivo.

Prophylactic effect of Enterococcus faecalis FK-23 preparation on experimental candidiasis in mice.

The prophylactic effects of heat-killed cells of Enterococcus faecalis FK-23 (FK-23 preparation) on experimental candidiasis were investigated in normal and leukopenic mice. In cyclophosphamide-induced leukopenic mice, oral or intraperitoneal administration of the FK-23 preparation at a daily dose of 1.25 or 5 mg/mouse for 3 consecutive days prior to Candida albicans infection significantly prolonged survival periods of the infected mice, and decreased viable counts of C. albicans recovered from their kidneys. In normal mice, the FK-23 preparation administered at dosages ranging from 0.63 to 10 mg/mouse/day for 3 consecutive days was ineffective, while in leukopenic mice, the FK-23 administered orally caused a facilitated recovery in the number of white blood cells including neutrophils. Furthermore, intraperitoneal administration of the FK-23 preparation into mice augmented the anti-Candida activity of immunocompromised peritoneal exudate cells obtained from the animals. These results suggested the potential usefulness of the FK-23 preparation as a prophylactic agent for the management of patients with opportunistic fungal infections.

Effect of orally administered heat-killed Enterococcus faecalis FK-23 preparation on neutropenia in dogs treated with cyclophosphamide

Dogs injected intravenously for 3 days with cyclophosphamide (CY) at a dose of 10 mg/kg were given 100 mg/kg of Enterococcus faecalis FK-23 preparation (FK-23) perorally for 14 days to confirm the beneficial effects of the latter drug in neutropenic dogs when orally administered. Although FK-23 treatment did not inhibit CY-induced neutropenia, it augmented neutrophil-reconstituting capacity in these dogs. Increases in the myeloid/ erythroid ratio and neutrophilic lineages were found in the bone marrow of FK-23 administered dogs. The oral administration significantly restored the reduced activity of neutrophil phagocytosis and chemiluminescence in dogs treated with CY. These findings indicate that FK-23 administered perorally not only augments neutrophil reconstitution through the activation of bone marrow but also functions in dogs treated with CY. It may thus be a useful supportive agent to reduce the adverse side-effects associated with the administration of chemotherapeutic agents such as CY.

Augmented ability of spleen cells to produce interferons and prevention from lethal infection of herpes simplex virus in mice orally treated with Enterococcus faecalis preparation, FK-23

Effects of the oral or intraperitoneal administration of an Enterococcus preparation, FK-23, to mice on the interferon (IFN) production by their spleen cells and on the host defense against the infection with herpes simplex virus (HSV)-1 were examined. Spleen cells were obtained from the mice intraperitoneally treated with cyclophosphamide (CY) and subsequently orally administered FK-23 preparation, and then cultured with phytohemagglutinin-P or bacterial lipopolysaccharide in vitro. They produced higher titers IFN than those obtained from control mice which were not treated with the FK-23 preparation. The IFN activity was neutralized mainly by antiIFN-beta antibody. Correspondingly, oral (5 mg/mouse) or intraperitoneal (1 mg/mouse) administration of the FK-23 preparation protected some of the CY-pretreated mice from death by HSV-1 infection.

Optimal doses of Enterococcal preparation (FK-23) Supplemented Perorall for Stimulation of Leukocyte Reconstitution in Dogs Treated with Cyclophospamide.

Optimal doses of orally supplemented heat-killed Enterococcus faecalis FK-23 preparation (FK-23) were evaluated in dogs treated with cyclophosphamide (CY). Leukocyte reconstitution was stimulated by the supplement of 100 mg/kg of FK-23 through an induction of neutrophilia, and the treatment of 10 mg/kg of FK-23 induced mild neutrophilia in dogs tested. However, the reconstitution was not stimulated by the treatment of 200 or 400 mg/kg of the drug. Although the effects of FK-23 appeared to be milder than those of recombinant human granulocyte colony stimulating factor (rhG-CSF), there was no significant difference in the leukocyte reconstitution between the two substances. An appropriate dose of FK-23 is 100 mg/kg for augmentation of leukocyte reconstituting capacity in dogs treated with CY.

Enterococcus faecalis FK-23株加熱死菌体標品を経口摂取した無菌マウスにおける腫瘍壊死因子産生能の増強

The effects of a preparation of heat-killed cells of Enterococcus faecalis FK-23 taken orally on the production of tumor necrosis factor (TNF) were examined in germ-free, and SPF ICR mice. These mice had TNF in their sera 1h after an intravenous injection of the FK-23 preparation or bacterial lipopolysaccharide. The mean TNF level in germ-free mice after the injection was significantly higher at day 0 after the mice ate feed containing the FK-23 preparation on days-7 to -3, with the usual feed given afterward until day 0. In the SPF ICR mice, TNF production was not changed when feed containing the FK-23 preparation was given. These results indicate that the oral intake of the FK-23 preparation had immunomodulating effects.

Effect of orally administered heat-killed Enterococcus faecalis FK-23 preparation on leukopenia in mice treated with cyclophosphamide.

Cyclophosphamide (CY) treated mice were orally administered heat-killed Enterococcus faecalis FK-23 preparation (FK-23) to define the effect of FK-23 on leukopenia associated with chemotherapy. FK-23 had no inhibiting effect on CY induced leukopenia, whereas it augmented leukocyte reconstitution in CY-treated mice. The percentage of neutrophils increased in the mice orally given FK-23. Furthermore, an increase in a myeloid/erythroid ratio and neutrophilic lineages was found in bone marrow of FK-23 treated mice. These findings suggest that FK-23 may have a potent effect on the augmentation of leukocyte reconstituting capacity in patients receiving chemotherapy.

Antitumor activity of Enterococcus faecalis FK-23 preparation against murine syngeneic tumors

The antitumor activity of a preparation of heat-killed cells of Enterococcus faecalis, FK-23. Intraperitoneal injection of the preparation prolonged the lifespan of C3H/He N mice which were intraperitoneally inoculated with MM46 mammary carcinoma. Not only intraperitoneal but also oral administration of the FK-23 preparation inhibited the growth of these carcinomas inoculated intradermally. The tumor-bearing mice produced tumor necrosis factor (TNF) in their sera 2 h after intravenous injection of OK432. This TNF level increased after the mice were fed with food supplemented with the FK-23 preparation. Additionally, the FK-23 preparation inhibited the growth of Meth A fibrosarcoma in cyclophosphamide-treated BALB/c mice.

Activity of Enterococcus faecalis (FK-23) preparation as a biological response modifier

The biological activity of a preparation of heat killed cells of Enterococcus faecalis, FK-23 which was isolated from the feces of a healthy human, was investigated in C3H/He mice. Intraperitoneal injection of the preparation caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice 6 h later. As a parameter of the activation of macrophages, the effect of the FK-23 preparation on the production of tumor necrosis factor (TNF) was examined. The mice were given two consecutive intravenous injections of the preparation at a dose of 10 micrograms/mouse and, 3 h later, of 300 micrograms/mouse. The TNF level in the sera reached 99 U/ml in mice 2 h after the second injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro and increased the capacity of neutrophils to adhere to plastic plates and to release active oxygens, but did not induce blastogenic transformation of lymphocytes. These results suggest that the FK-23 preparation is a biological response modifier (BRM) with various activities on phagocytes similar to a streptococcal antitumor agent, OK432.