scholarly journals Probiotic supplementation reduces systemic inflammation in dialysis patients: the effect on circulating regulatory T-cells and pro-inflammatory monocytes

Author(s):  
Eunho Choi ◽  
Jihyun Yang ◽  
Geun-Eog Ji ◽  
Myeong Soo Park ◽  
Yeongje Seong ◽  
...  

Abstract BackgroundEmerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients.MethodsTwenty-two patients with maintenance HD were enrolled (Institutional Review Board No. 2018AN0346). These patients were treated twice a day with 2.0 × 1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ pro-inflammatory monocytes, and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation.ResultsFecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and IL-6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ pro-inflammatory monocytes (310 vs. 194/mm2, p < 0.05).ConclusionProbiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in pro-inflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.Trial registrationThe study was retrospectively registered in Clinical Research Information Service (CRIS) (KCT0005417) (09/09/2020).

2019 ◽  
Vol 10 (1) ◽  
pp. 55-67 ◽  
Author(s):  
W.-G. Kim ◽  
G.-D. Kang ◽  
H.I. Kim ◽  
M.J. Han ◽  
D.-H. Kim

This study aimed to examine whether probiotics, which suppressed the differentiation of splenic T cells into type 2 helper T (Th2) cells and induced into regulatory T cells in vitro, alleviate allergic rhinitis (AR) and gut microbiota disturbance. We isolated Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 from human faecal microbiota and kimchi, respectively, and examined their effects on ovalbumin (OVA)-induced AR and gut microbiota disturbance in mice. Treatment with IM55, IM76, or their probiotic mixture (PM) significantly reduced OVA-induced allergic nasal symptoms and blood immunoglobulin E (IgE) levels in mice. These also reduced OVA-induced interleukin (IL)-4 and IL-5 levels in nasal tissues and bronchoalveolar lavage fluid (BALF) but increased OVA-suppressed IL-10 levels. Treatment with IM55, IM76, or PM reduced OVA-induced increase in the populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of regulatory T cells in the BALF. Treatment with IM55, IM76, or PM also inhibited OVA-induced expression of IL-5 in lung and colon tissues and restored OVA-disturbed composition of gut microbiota Proteobacteria, Bacteroidetes, and Actinobacteria. These results suggest that IM55 and IM67 can alleviate AR by restoring Th2/Treg imbalance and gut microbiota disturbance.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 229-229
Author(s):  
Dennis Leveson-Gower ◽  
Janelle Olson ◽  
Emanuela I Sega ◽  
Jeanette Baker ◽  
Robert Zeiser ◽  
...  

Abstract Abstract 229 NKT cells, a subset of which are CD1d reactive, play an important immunoregulatory role in suppressing dysfunctional immune reactions, including graft-versus-host disease (GVHD). To explore the biological activity and mechanism of donor-type NKT in suppression of GVHD, we utilized highly purified (>95%) populations of donor (C57Bl6; H-2b) NKT (DX5+TCR+CD4+) cells adoptively transferred into lethally irradiated recipient (Balb/c; H-2d) animals with T cell depleted bone marrow (TCD-BM). Highly purified (>95%) NKT cells (5.5×105) from luciferase positive (luc+) C57BL/6 mice were infused into lethally irradiated Balb/c recipients with TCD-BM(5×106) from wild-type (WT) C57BL/6 mice, and the animals were monitored by bioluminescence imaging (BLI). By day 4 after transfer, an NKT derived signal was observed in spleen and lymph node (LN) sites, and between days 7 and 10, NKT had also migrated to the skin. Total photons emitted peaked near day 25 after transplantation, followed by a steady decline. To assess the impact of donor-type NKT cells on GVHD induction by conventional CD4+ and CD8+ T cells (Tcon), we co-transferred various doses of highly purified WT NKT at day 0 with TCD-BM, followed by 5×105 luc+Tcon/animal on day 2. As few as 2.5×104 NKT cells significantly improved survival of mice receiving 5×105 Tcon. Animal survival with Tcon only was 20% and for Tcon with NKT cells was 74%(p=0.0023). In contrast to what is observed with CD4+CD25+FoxP3+ regulatory T cells (Treg), the NKT cells did not suppress Tcon proliferation assayed by both in vivo BLI and in a mixed-leukocyte reaction. Analysis of serum cytokines with or without 2.5×104 NKT, following HCT with TCD-BM and Tcon, indicated the addition of NKT cells resulted in elevated levels of INF-γ, IL-5, and IL-6 in serum; significant differences were not observed in serum levels of IL-2, IL-4, IL-10, IL-17, or TNF-α. Intracellular levels of cytokines in Tcon were analyzed from the same groups. At 8 days after HCT, mice receiving NKT had fewer TNFα-positive cells in LNs (CD4: 45% to 27%; CD8 36% to 24%); by day 11, however, TNFαa levels between groups were equivalent. IFN-γ levels, which were high in both NKT treated and untreated groups at day 8 (85%-95%), decreased significantly in NKT treated mice by day 11 (CD4: 40%; CD8: 43%), but were abundant in Tcon only mice (CD4: 78%; CD8: 80%) (p=.0001). No significant changes were found in the intracellular levels of IL-2, IL-4, IL-5, IL-10, or IL-17 of Tcon in the presence or absence of NKT cells. NKT from both IL-4 -/- and IFN-γ -/- mice were less effective at suppressing GVHD than WT NKT, implicating these cytokines in the suppressive mechanism. Finally, we found that NKT do not have a major impact on the graft-versus-tumor effect of Tcon against a luc+ BCL-1 tumor. These studies indicate that NKT persist in vivo upon adoptive transfer and suppress GVHD, even at extremely low cell numbers, which is important given the relative paucity of this cell population. The mechanisms of GVHD suppression appear to be distinct to those of Treg and involve the production of IL-4 and IFN-γ by NKT resulting in a decrease in Tcon, which produce pro-inflamatory cytokines. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 133 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Satoru Watanabe ◽  
Norifumi Ide ◽  
Hatsue Ogawara ◽  
Akihiko Yokohama ◽  
Takeki Mitsui ◽  
...  

Introduction: In some previous studies, vitamin B12 treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (Tregs), were examined before and after vitamin B12 treatment in PA patients. Patients and Methods: The percentages of CD4, CD8, Th1, Th2 and Tregs were examined in 23 PA patients before vitamin B12 treatment, in 23 other PA patients after vitamin B12 treatment and in 28 healthy controls. Results: The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of Tregs in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05). Conclusions: The percentage of Tregs was significantly higher in PA patients than in normal subjects, and this high Treg percentage was not different before and after vitamin B12 treatment. Other immunological alterations also did not recover after vitamin B12 treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B12 deficiency.


2009 ◽  
Vol 36 (9) ◽  
pp. 1930-1936 ◽  
Author(s):  
AGOTA HAJAS ◽  
PETER SZODORAY ◽  
SANDOR BARATH ◽  
SANDOR SIPKA ◽  
SZILARD REZES ◽  
...  

Objective.To investigate the frequency of sensorineural hearing loss (SNHL) in patients with mixed connective tissue disease (MCTD).Methods.The study population consisted of 71 patients with MCTD (69 female; 2 male), with a mean age of 57.1 ± 7.9 years and a mean disease duration of 14.5 ± 8.0 years. All patients underwent audiological evaluation that included pure tone and speech audiometry. In addition, the systemic manifestations of the disease and drug therapy were recorded. All patients were tested for presence of autoantibodies. Fifty-one age-matched healthy subjects served as controls.Results.SNHL was found in 33 (46.4%) of the 71 patients with MCTD. There was no correlation between SNHL and age and disease duration. An association was found between Raynaud’s phenomenon (p < 0.03), secondary antiphospholipid syndrome (APS) (p < 0.05), and SNHL. MCTD patients with SNHL had higher serum levels of anti-U1RNP (p < 0.05), antiendothelial cell antibodies (p < 0.001), and IgG type anticardiolipin antibodies (p < 0.0001) than patients without SNHL. Serum levels of interferon-γ and tumor necrosis factor-α were increased in MCTD patients with SNHL compared to patients without SNHL. The absolute number of natural (CD4+CD25highFoxP+) regulatory T cells (Treg) was lower compared to patients without SNHL.Conclusion.In MCTD, SNHL is a specific organ manifestation and appears frequently. We have found that pathogenic autoantibodies, decreased levels of regulatory T cells, and overexpression of proinflammatory cytokines may play a role in the pathogenesis of immune mediated inner ear disorders in MCTD.


Author(s):  
Eunho Choi ◽  
Jihyun Yang ◽  
Geun-Eog Ji ◽  
Myeong Soo Park ◽  
Yeongje Seong ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14684-e14684
Author(s):  
Teruo Sasatomi ◽  
Takafumi Oochi ◽  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Kazuo Shirouzu

e14684 Background: Many multiple anti cancer drugs regimens have been established for metastaticcolorectal cancer recently. We investigated cellular immunoreaction of these patients to their cancer. Methods: 32 metastatic colorectal cancer patients have been started chemotherapies. Their PBMCs were harvested and investigated their character by Fac scan with fluorescent labeled antibodies (CD3,CD8, CD4, CD25, Foxp3) at before and after chemotherapy. Results: After chemotherapy, both CTLs(CD3, CD8 positive) and regulatory T cells (CD4, CD25, Foxp3 positive) were decreased in number among all patients. On the other hand, CTL/T reg ratio were significantly increased among tumor marker decreased patients and significantly decreased among tumor marker increased or stable patients. CEA levels among 85.7% of increased CTL/T reg ratio patients became to decrease less thanhalf. CEA levels among 66.7% of decreased CTL/T reg ratio patients became to increase or to be stable, if their regimens have not been changed. The Reactive Rate of chemotherapy of CTL/T reg ratio increased patients was significantly higher than that of ratio decreased or stable patients. (P=0.021) The Disease Control Rate of chemotherapy of CTL/T reg ratio increased patients was higher than that of ratio decreased patients. Both resectability rate of liver metastatic lesion and early tumor shrinkage rate were higher at the CTL/T reg ratio increased patients group than at the other patients group. Conclusions: We found that the CTL/T reg ratios of PBMC in metastatic colorectal cancer patients were useful for prediction of the effect of chemotherapy.


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