Changes in the Intestinal Microbiota and Systemic Immune Responses by Dietary 1-Kestose Supplementation in Healthy Dogs

2020 ◽  
Vol 16 (1) ◽  
pp. 7-15
Author(s):  
T. Tochio ◽  
Y. Kadota ◽  
Y. Asami ◽  
R. Azuma ◽  
R. Oishi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Serum Antibody ◽  
Flow Cytometric Analysis ◽  
Allergic Diseases ◽  
Food Material ◽  
Quantification Analysis ◽  
Antibody Titers ◽  
Healthy Dogs ◽  
System 1

1-Kestose is a trisaccharide prebiotic that modifies immune responses in humans and rodents with allergic diseases by altering the intestinal microbiota. In the present study, we examined the effects of 1-kestose supplementation on the intestinal microbiota, peripheral lymphocyte subsets, and antibody production in healthy dogs. Fecal IgA levels and serum antibody titers against the rabies vaccine were not significantly affected by 1-kestose supplementation. In a flow cytometric analysis, the percentage of T cells among total lymphocytes decreased, whereas that of B cells increased in supplemented dogs. A metagenomic analysis of the intestinal microbiota showed that the proportion of Bifidobacterium increased, while that of Lactobacillus did not decrease in supplemented dogs. Furthermore, a quantification analysis using real-time polymerase chain reaction showed that the proportion of Bifidobacterium increased in supplemented dogs. These results suggest that 1-kestose supplementation induced modifications in the intestinal microbiota of dogs, which presumably enhanced the immune system. 1-Kestose may be a useful food material as a prebiotic for dogs.

scholarly journals Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults

2021 ◽  
Vol 2 ◽  
Author(s):  
Chris P. Verschoor ◽  
Laura Haynes ◽  
Graham Pawelec ◽  
Mark Loeb ◽  
Melissa K. Andrew ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Standard Dose ◽  
Serum Antibody ◽  
High Dose ◽  
Post Vaccination ◽  
Antibody Titers ◽  
Virus Influenza

Background: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that granzyme B (GrB) activity in influenza A/H3N2 challenged peripheral blood mononuclear cells (PBMC) correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection.Methods: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n = 582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20–40 years, n = 79) received SD-SVV. At 0, 4, 10, and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, and in older adults, we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose.Results: Prior to vaccination, younger compared to older adults produced significantly higher IFNγ, IL-10, and iGrB levels. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups; all three groups showed a significant iGrB response to vaccination. In a regression analysis, frailty was associated with lower IFNγ levels, whereas female sex and HD-SVV with higher IL-10 levels. Age and SD-SVV were associated with lower iGrB levels. The effect of prior season influenza vaccination was decreased iGrB levels, and increased IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers.Conclusion: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.Clinical Trial Registration: ClinicalTrials.gov (NCT02297542).

THE ROLE OF PHAGE THERAPY IN THE FORMATION OF THE INTESTINAL MICROECOSYSTEM

2020 ◽  
pp. 183-191
Author(s):  
Gladkov S.F. ◽  
Perevoshchikova N.K. ◽  
Chernykh N.S. ◽  
Pichugina Yu.S. ◽  
Surkova M.A.
Keyword(s):  
Intestinal Microbiota ◽  
Allergic Diseases ◽  
Evidence Base ◽  
Immunological Tolerance ◽  
Convincing Evidence ◽  
Selective Decontamination ◽  
Genetic Characteristics ◽  
Treatment And Prevention ◽  
Intestinal Infections ◽  
The Individual

The current adverse situation associated with the presence of a pandemic of allergic diseases is due to the lack of a scientifically based concept of treatment and prevention. The increased interest of researchers from different countries in the formation of immunological tolerance by modeling the intestinal microbiota is of high importance. Methods of influence on the microbial communities of the child's intestine should be as delicate as possible, taking into account the individual genetic characteristics of the microecosystem and the possibility of anaphylaxis. Until now, probiotic drugs have been widely used to correct dysbiosis, but data is gradually accumulating that there is no convincing evidence base for their use for the treatment and prevention of atopy. The use of bacteriophages is very relevant and one of the promising, actively studied areas of correction of intestinal biocenosis today, which are an alternative to antibiotic and probiotic medications. Selective decontamination of representatives of opportunistic flora, as the main factor in the implementation of the atopic phenotype, makes it possible to preserve and accelerate the formation of a unique and individual composition of the intestinal microbiota of the child, which can form an immunoregulatory balance. More than a century of experience in the use of bacteriophages indicates the safety of their use. Today, bacteriophages are actively used in various fields of practical medicine − obstetrics-gynecology, perinatology, urology, pediatric otorhinolaryngology, in the treatment of purulent-septic and intestinal infections. In some cases, bacteriophages are very effective against antibiotic-resistant pathogens. The active personalized use of bacteriophages in real clinical practice will make it possible to solve a number of serious, long-standing health problems in the Russian Federation and to win a world priority in this direction.

scholarly journals Differential response of digesta- and mucosa-associated intestinal microbiota to dietary insect meal during the seawater phase of Atlantic salmon

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Yanxian Li ◽  
Leonardo Bruni ◽  
Alexander Jaramillo-Torres ◽  
Karina Gajardo ◽  
Trond M. Kortner ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Immune Responses ◽  
Intestinal Microbiota ◽  
Barrier Function ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Association Analyses ◽  
Distal Intestine ◽  
Expression Of Genes ◽  
Rrna Gene Sequencing

Abstract Background Intestinal digesta is commonly used for studying responses of microbiota to dietary shifts, yet evidence is accumulating that it represents an incomplete view of the intestinal microbiota. The present work aims to investigate the differences between digesta- and mucosa-associated intestinal microbiota in Atlantic salmon (Salmo salar) and how they may respond differently to dietary perturbations. In a 16-week seawater feeding trial, Atlantic salmon were fed either a commercially-relevant reference diet or an insect meal diet containing ~ 15% black soldier fly (Hermetia illucens) larvae meal. The digesta- and mucosa-associated distal intestinal microbiota were profiled by 16S rRNA gene sequencing. Results Regardless of diet, we observed substantial differences between digesta- and mucosa-associated intestinal microbiota. Microbial richness and diversity were much higher in the digesta than the mucosa. The insect meal diet altered the distal intestinal microbiota resulting in higher microbial richness and diversity. The diet effect, however, depended on the sample origin. Digesta-associated intestinal microbiota showed more pronounced changes than the mucosa-associated microbiota. Multivariate association analyses identified two mucosa-enriched taxa, Brevinema andersonii and Spirochaetaceae, associated with the expression of genes related to immune responses and barrier function in the distal intestine, respectively. Conclusions Our data show that salmon intestinal digesta and mucosa harbor microbial communities with clear differences. While feeding insects increased microbial richness and diversity in both digesta- and mucosa-associated intestinal microbiota, mucosa-associated intestinal microbiota seems more resilient to variations in the diet composition. To fully unveil the response of intestinal microbiota to dietary changes, concurrent profiling of digesta- and mucosa-associated intestinal microbiota is recommended whenever feasible. Specific taxa enriched in the intestinal mucosa are associated to gene expression related to immune responses and barrier function. Detailed studies are needed on the ecological and functional significance of taxa associated to intestinal microbiota dwelling on the mucosa.

scholarly journals Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jiaying Wu ◽  
Yuyu Zhang ◽  
Hongyu Yang ◽  
Yuefeng Rao ◽  
Jing Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Neurological Disorders ◽  
Digestive System ◽  
Hygiene Hypothesis ◽  
Host Susceptibility ◽  
Immune Disorders ◽  
The Central Nervous System ◽  
Symbiotic Microbiota

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people’s attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).

scholarly journals Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic Cells

2000 ◽  
Vol 192 (7) ◽  
pp. 931-942 ◽  
Author(s):  
Lynn G. Hannum ◽  
Ann M. Haberman ◽  
Shannon M. Anderson ◽  
Mark J. Shlomchik
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
B Cell ◽  
Immune Complexes ◽  
Germinal Center ◽  
Serum Antibody ◽  
Cell Formation ◽  
Immunoglobulin M ◽  
Follicular Dendritic Cells ◽  
Follicular Dendritic

Serum antibody (Ab) can play several roles during B cell immune responses. Among these is to promote the deposition of immune complexes (ICs) on follicular dendritic cells (FDCs). ICs on FDCs are generally thought to be critical for normal germinal center (GC) formation and the development and selection of memory B cells. However, it has been very difficult to test these ideas. To determine directly whether FDC-bound complexes do indeed function in these roles, we have developed a transgenic (Tg) mouse in which all B lymphocytes produce only the membrane-bound form of immunoglobulin M. Immune Tg mice have 10,000-fold less specific Ab than wild-type mice and lack detectable ICs on FDCs. Nonetheless, primary immune responses and the GC reaction in these mice are robust, suggesting that ICs on FDCs do not play critical roles in immune response initiation and GC formation. Moreover, as indicated by the presence and pattern of somatic mutations, memory cell formation and selection appear normal in these IC-deficient GCs.

scholarly journals Dairy Heifers Naturally Exposed toFasciola hepaticaDevelop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
John Graham-Brown ◽  
Catherine Hartley ◽  
Helen Clough ◽  
Aras Kadioglu ◽  
Matthew Baylis ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Serum Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mixed Effect ◽  
Content Type ◽  
Grazing Season ◽  
Type 2 Immune Response

ABSTRACTFasciola hepaticais a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response toF. hepaticafollowing natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed toF. hepaticainfection. Cohorts of replacement dairy heifer calves (n= 42) with no prior exposure toF. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through anF. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge withF. hepatica. This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

scholarly journals Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 500
Author(s):  
Yoshikazu Honda-Okubo ◽  
Jeremy Baldwin ◽  
Nikolai Petrovsky
Keyword(s):  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Oral Polio Vaccine ◽  
Antigen Dose ◽  
Polio Vaccine ◽  
Antibody Titers ◽  
Dose Sparing ◽  
Sparing Effect ◽  
Eradicate Polio

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Live oral polio vaccine (OPV) played a role in the reduction in polio case numbers; however, the risk of OPV developing into circulating vaccine-derived poliovirus makes it unsuitable for eradication programs. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; however, TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. This study examined whether the incorporation of the novel polysaccharide adjuvant, Advax-CpG, could boost the immunogenicity of two TIPV vaccines, (i) a commercially available polio vaccine (IPOL®, Sanofi Pasteur) and (ii) a new TIPV formulation developed by Statens Serum Institut (SSI). Mice were immunized intramuscularly based on recommended vaccine dosage schedules and serum antibody titers were followed for 12 months post-immunization. Advax-CpG significantly enhanced the long-term immunogenicity of both TIPV vaccines and had at least a 10-fold antigen dose-sparing effect. An exception was the poor ability of the SSI TIPV to induce serotype type 1 neutralizing antibodies. Immunization with monovalent IPVs suggested that the low type 1 response to TIPV may be due to antigen competition when the type 1 antigen was co-formulated with the type 2 and 3 antigens. This study provides valuable insights into the complexity of the formulation of multivalent polio vaccines and supports the further development of adjuvanted antigen-sparing TIPV vaccines in the fight to eradicate polio.

scholarly journals Miquelianin Inhibits Allergic Responses in Mice by Suppressing CD4+ T Cell Proliferation

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1120
Author(s):  
Dae Woon Choi ◽  
Sun Young Jung ◽  
Gun-Dong Kim ◽  
So-Young Lee ◽  
Hee Soon Shin
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Mouse Model ◽  
Immune Responses ◽  
Reactive Oxygen Species Generation ◽  
Allergic Diseases ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
T Cell Proliferation ◽  
Heme Oxygenase 1

Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.

scholarly journals Formation of Autoimmune Lesions Is Independent of Antibiotic Treatment in NOD Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 3239
Author(s):  
 Mami Sato ◽  
Rieko Arakaki ◽  
Hiroaki Tawara ◽  
Takaaki Tsunematsu ◽  
Naozumi Ishimaru
Keyword(s):  
Intestinal Microbiota ◽  
Flow Cytometric Analysis ◽  
Nod Mice ◽  
Antibiotic Administration ◽  
T And B Cells ◽  
Spleen Cells ◽  
Flow Cytometric ◽  
Enteral Microbiota ◽  
The Relationship

The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function.

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