Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients

Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone ‘curative resection’ and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 × 1010 colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 × 1010 colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-α and interferon-γ (IFN-γ) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-β1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0·05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-γ at T3 (P < 0·05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.

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Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-γ and breast milk transforming growth factor-β and immunoglobin A detection

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.2008.03061.x ◽

2008 ◽

Vol 38 (10) ◽

pp. 1606-1614 ◽

Cited By ~ 143

Author(s):

S. L. Prescott ◽

K. Wickens ◽

L. Westcott ◽

W. Jung ◽

H. Currie ◽

...

Keyword(s):

Growth Factor ◽

Breast Milk ◽

Cord Blood ◽

Transforming Growth Factor ◽

Lactobacillus Rhamnosus ◽

Transforming Growth Factor Β ◽

Interferon Γ ◽

Bifidobacterium Lactis ◽

In Pregnancy

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Gnotobiotic Mouse Immune Response Induced by Bifidobacterium sp. Strains Isolated from Infants

Applied and Environmental Microbiology ◽

10.1128/aem.01261-07 ◽

2007 ◽

Vol 74 (3) ◽

pp. 660-666 ◽

Cited By ~ 71

Author(s):

Odile Ménard ◽

Marie-José Butel ◽

Valérie Gaboriau-Routhiau ◽

Anne-Judith Waligora-Dupriet

Keyword(s):

Immune System ◽

Transforming Growth Factor ◽

Bifidobacterium Longum ◽

Interleukin 4 ◽

Fecal Flora ◽

Gene Expressions ◽

Tnf Α ◽

Intestinal Immune System ◽

Ifn Γ ◽

The Impact

ABSTRACT Bifidobacterium, which is a dominant genus in infants’ fecal flora and can be used as a probiotic, has shown beneficial effects in various pathologies, including allergic diseases, but its role in immunity has so far been little known. Numerous studies have shown the crucial role of the initial intestinal colonization in the development of the intestinal immune system, and bifidobacteria could play a major role in this process. For a better understanding of the effect of Bifidobacterium on the immune system, we aimed at determining the impact of Bifidobacterium on the T-helper 1 (TH1)/TH2 balance by using gnotobiotic mice. Germfree mice were inoculated with Bifidobacterium longum NCC2705, whose genome is sequenced, and with nine Bifidobacterium strains isolated from infants’ fecal flora. Five days after inoculation, mice were killed. Transforming growth factor β1 (TGF-β1), interleukin-4 (IL-4), IL-10, and gamma interferon (IFN-γ) gene expressions in the ileum and IFN-γ, tumor necrosis factor alpha (TNF-α), IL-10, IL-4, and IL-5 secretions by splenocytes cultivated for 48 h with concanavalin A were quantified. Two Bifidobacterium species had no effect (B. adolescentis) or little effect (B. breve) on the immune system. Bifidobacterium bifidum, Bifidobacterium dentium, and one B. longum strain induced TH1 and TH2 cytokines at the systemic and intestinal levels. One B. longum strain induced a TH2 orientation with high levels of IL-4 and IL-10, both secreted by splenocytes, and of TGF-β gene expression in the ileum. The other two strains induced TH1 orientations with high levels of IFN-γ and TNF-α splenocyte secretions. Bifidobacterium's capacity to stimulate immunity is species specific, but its influence on the orientation of the immune system is strain specific.

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Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial

Rheumatology ◽

10.1093/rheumatology/kez160 ◽

2019 ◽

Vol 58 (11) ◽

pp. 1985-1990 ◽

Cited By ~ 5

Author(s):

Thais Fernandes Marighela ◽

Maria Izabel Arismendi ◽

Valdecir Marvulle ◽

Milena Karina Coló Brunialti ◽

Reinaldo Salomão ◽

...

Keyword(s):

Los Angeles ◽

Controlled Trial ◽

Gastrointestinal Symptoms ◽

Lactobacillus Rhamnosus ◽

Bifidobacterium Lactis ◽

Immune Parameters ◽

Colony Forming Units ◽

Gi Symptoms ◽

The University ◽

To Receive

AbstractObjectivesChanges in the intestinal microbiota have been associated with the pathogenesis of SSc. Probiotics act by modulating the microbiome and the immune response. This study aimed to evaluate the efficacy of probiotics on gastrointestinal (GI) symptoms and immune responses in SSc patients.MethodsPatients with SSc with a moderate–severe total score on the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA GIT 2.0) instrument were randomly assigned to receive a daily dose of probiotics (Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophillus and Bifidobacterium lactis, 109 colony-forming units per capsule) or placebo for 8 weeks. The primary endpoint was improvement in the UCLA GIT 2.0 total score after 8 weeks. Secondary outcomes included changes in Th1, Th2, Th17 and regulatory T cell circulating levels and in the HAQ Disability Index (HAQ-DI) score. Parameters were assessed at baseline and after 4 and 8 weeks of treatment.ResultsA total of 73 patients were randomized to receive probiotics (n = 37) or placebo (n = 36). After 8 weeks, there was no difference in the UCLA GIT 2.0 score between the two groups. At week 8, the probiotic group showed a significant decrease in the proportion of Th17 cells compared with placebo (P = 0.003). There was no difference in the proportion of Th1, Th2 and regulatory T cells or in the HAQ-DI score between the groups.ConclusionProbiotics did not improve GI symptoms in SSc patients. The reduction in Th17 cell levels suggests an immunomodulatory effect of probiotics on SSc.Trial registrationClinicalTrials.gov (http://clinicaltrials.gov), NCT 02302352.

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Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension

Mediators of Inflammation ◽

10.1155/2015/349215 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Kohei Kotani ◽

Joji Kawabe ◽

Hiroyasu Morikawa ◽

Tomohiko Akahoshi ◽

Makoto Hashizume ◽

...

Keyword(s):

Arachidonic Acid ◽

Portal Hypertension ◽

Immune System ◽

Nucleic Acid ◽

System Analysis ◽

Acid Metabolism ◽

Transforming Growth Factor ◽

Idiopathic Portal Hypertension ◽

Nucleic Acid Metabolism ◽

Prostaglandin E

The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-β, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

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Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis

British Journal Of Nutrition ◽

10.1079/bjn20041289 ◽

2004 ◽

Vol 92 (6) ◽

pp. 931-938 ◽

Cited By ~ 78

Author(s):

Monika Roller ◽

Angelo Pietro Femia ◽

Giovanna Caderni ◽

Gerhard Rechkemmer ◽

Bernhard Watzl

Keyword(s):

Colon Cancer ◽

Nk Cell ◽

Human Subjects ◽

Lactobacillus Rhamnosus ◽

Colon Carcinogenesis ◽

Interferon Γ ◽

Experimental Models ◽

Immune Functions ◽

Intestinal Immunity ◽

Bifidobacterium Lactis

Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0·01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0·01) and in MLN of rats not treated with AOM (P<0·05). Interferon-γ production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0·05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0·01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.

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Assessment of Benefits and Risks of Probiotics in Processed Cerealbased Baby Foods Bifidobacterium Lactis Bb12

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2021/v13i430406 ◽

2021 ◽

pp. 58-60

Author(s):

Ragnhild Halvorsen ◽

Judith Narvhus ◽

Jørgen Lassen ◽

Tore Midtvedt ◽

Jarle Rugtveit ◽

...

Keyword(s):

Small Intestine ◽

Immune System ◽

Food Safety ◽

Health Effects ◽

Age Groups ◽

Daily Intake ◽

Positive Health ◽

Bifidobacterium Lactis ◽

Small Children ◽

Baby Foods

The Norwegian Scientific Committee for Food Safety (VKM) has appointed an ad hoc-group of experts to answer a request from the Norwegian Food Safety Authority regarding benefit and risk assessment of B. lactis Bb12 in baby foods focusing on the age groups 4-6 months, 612 months and 1-3 years. This assessment is based on the literature provided by the notifier as well as that found by a MEDLINE search. An notification for use of processed cereal-based baby foods (from now on called cereals) intended for infants and small children supplemented with the microorganism Bifidobacterium lactis (B. lactis) Bb12 in Norway initiated this work. Studies of potential hazards and positive health effects from cereals containing B. lactis Bb12 intended for infants and young children have not been reported in the available literature. However, reports on safety of and positive health effects from infant and follow on formula supplemented with B. lactis Bb12 are available and have been assessed by VKM. In most of these clinical studies B. lactis Bb12 was administered in combination with other probiotic strains. Clinical studies report no serious adverse events of infant formula supplemented with B. lactis Bb12. The effect of long term daily consumption of such supplemented formula by the actual age groups is not known. A few studies have demonstrated some effect of supplementing baby food with probiotics, including B. lactis Bb12, on diarrhoea and atopic eczema while other studies do not show such effects. Thus, the scientific evidence for a favourable effect of supplementing formula or solid food with B. lactis Bb12, is weak and in some cases lacking. There are no studies demonstrating a positive effect of cereals supplemented with B. lactis Bb12 intended for infants and small children. Several health claims related to probiotics have been assessed by EFSA, including claims on reduction of gastro-intestinal discomfort, normal functioning of the alimentary tract, building of the natural intestinal barrier, improvement of the general immunity, mental and cognitive developments of children and immune system of children during growth. In the opinions so far, EFSA has concluded that a cause and effect relationship has not been established between the consumption of the probiotic containing products and the claimed effect. None of the products assessed so far contained B. lactis Bb12 (1 November 2009). Commercially produced cereals are frequent given to infants and small children in Norway from an early age and this is particularly important for the establishment of the intestinal bacterial flora and the development of the intestinal mucosal immune system. According to the notifier, one portion (25gram) of the cereal powder contains 1 x 109 B. lactis Bb12 in monoculture. Taking into consideration that the daily intake is often greater than one portion of cereals, even in infants below 6 months of age, this would represent a daily intake of 1-2 x 109 cfu B. lactis Bb12 for an infant 4-6 months and even more in infants above 6 months. If a considerable amount of the B. lactis Bb12 survives the transport to the small intestine, it would represent a dominating and monocultural supply, often several times a day, to the small intestine. The immaturity and vulnerability of the intestinal microbiota and the immune system makes the two lowest age groups, 4 – 6 and 6 – 12 months, at the highest risk of unwanted health effects due to the daily intake of probiotics.

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Mucin 16 and kallikrein 13 as potential prognostic factors in colon cancer: Results of an oncological 92-multiplex immunoassay

Tumor Biology ◽

10.1177/1010428319860728 ◽

2019 ◽

Vol 41 (7) ◽

pp. 101042831986072

Author(s):

Kajsa Björkman ◽

Harri Mustonen ◽

Tuomas Kaprio ◽

Caj Haglund ◽

Camilla Böckelman

Keyword(s):

Colon Cancer ◽

Confidence Interval ◽

Cancer Patients ◽

Poor Prognosis ◽

Transforming Growth Factor ◽

Prognostic Markers ◽

Hazard Ratio ◽

Rank Test ◽

Preoperative Serum ◽

Low Levels

Colon cancer represents one of the most common cancers in the world. Despite improved treatment, mortality remains high. In order to improve the assessment of prognosis for colon cancer patients, identifying new prognostic markers remains necessary. We analyzed preoperative serum samples from 148 colon cancer patients surgically treated at Helsinki University Hospital from 1998 through 2002 using a multiplex proximity extension assay (Oncology II panel, Olink Bioscience, Uppsala, Sweden), a panel constituting 92 immunological and oncological markers. We performed univariate and multivariate analyses on these patients and calculated the disease-specific survival among patients using the log-rank test for Kaplan–Meier estimates. In the univariate survival analysis of 92 biomarkers, 26 resulted in p < 0.1. Among these, eight biomarkers emerged as statistically significant (p < 0.05). Patients with low levels of kallikrein 13 had a poor prognosis. Moreover, patients with high levels of amphiregulin, carcinoembryonic antigen-related adhesion molecule 5, interleukin 6, mucin 16, syndecan 1, transforming growth factor alpha, and vimentin also had a poor prognosis. In the multivariate analysis, kallikrein 13 and mucin 16 emerged as independent prognostic markers. The role of kallikrein 13, a member of the serine protease kallikrein biomarker family, in tumorigenesis remains unclear. Mucin 16 is also known as carbohydrate antigen 125, a well-known ovarian cancer biomarker. Patients with low levels of kallikrein 13 (hazard ratio: 0.36; 95% confidence interval: 0.14–0.92; p = 0.033) and high levels of mucin 16 (hazard ratio: 3.15; 95% confidence interval: 1.68–5.93; p < 0.005) had a poor prognosis. Mucin 16 and kallikrein 13 represent independent prognostic markers for colon cancer. Furthermore, the clinical utility of mucin 16 and kallikrein 13 serum tests warrants additional investigation.

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IFN-γ Enhances the Therapeutic Effect of Mscs on Experimental Renal Fibrosis

10.21203/rs.3.rs-27575/v1 ◽

2020 ◽

Author(s):

Ryo Kanai ◽

Ayumu Nakashima ◽

Shigehiro Doi ◽

Tomoe Kimura ◽

Ken Yoshida ◽

...

Keyword(s):

Growth Factor ◽

Prostaglandin E2 ◽

Therapeutic Effect ◽

Renal Fibrosis ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Prostaglandin E ◽

Therapeutic Effects ◽

Ifn Γ ◽

Anti Inflammatory

Abstract Background:Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes may require a substantial period of time, leading to a delayed onset of MSCs therapeutic effects. Here, we investigatedwhetherpretreatment with IFN-γ potentiates the anti-fibrotic and anti-inflammatory activities of MSCs in an injured kidney. Methods:MSCs with or without IFN-γ treatment were injected into rats after ischemia-reperfusion injury (IRI) or unilateral ureter obstruction (UUO) to evaluate the therapeutic effect of IFN-γ-treated MSCs. In addition, we used conditioned medium obtained from IFN-γ-treated MSCs to investigate fibrotic change in cultured cells induced by transforming growth factor-β1 and phenotypic change of macrophages using THP-1 monocytes.Results:Administration of MSCs treated with IFN-γ strongly ameliorated renal fibrosis and inflammation in rat IRI and UUO models compared with that of untreated MSCs. In vitro experiments demonstrated that IFN-γ treatment enhanced the anti-fibrotic effects of MSCs by inhibiting the transforming growth factor-β1/Smad signaling pathway. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 induced polarization of immunosuppressive CD163-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ.Conclusions:Administration of MSCs treated with IFN-γ may represent a promising therapy to prevent the progression of renal fibrosis.

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