Fructose, glucose and fat interrelationships with metabolic pathway regulation and effects on the gut microbiota

The purpose of this 30-day feeding study was to elucidate the changes, correlations, and mechanisms caused by the replacement of the starch content of the AIN-93G diet (St) with glucose (G), fructose (F) or lard (L) in body and organ weights, metabolic changes and caecal microbiota composition in rats (Wistar, SPF). The body weight gain of rats on the F diet was 12% less (P = 0.12) than in the St group. Rats on the L diet consumed 18.6% less feed, 31% more energy and gained 58.4% more than the animals on the St diet, indicating that, in addition to higher energy intake, better feed utilisation is a key factor in the obesogenic effect of diets of high nutrient and energy density. The G, F and L diets significantly increased the lipid content of the liver (St: 7.01 ± 1.48; G: 14.53 ± 8.77; F: 16.73 ± 8.77; L: 19.86 ± 4.92% of DM), suggesting that lipid accumulation in the liver is not a fructose-specific process. Relative to the St control, specific glucose effects were the decreasing serum glucagon (–41%) concentrations and glucagon/leptin ratio and the increasing serum leptin concentrations (+26%); specific fructose effects were the increased weights of the kidney, spleen, epididymal fat and the decreased weight of retroperitoneal fat and the lower immune response, as well as the increased insulin (+26%), glucagon (+26%) and decreased leptin (–25%) levels. This suggests a mild insulin resistance and catabolic metabolism in F rats. Specific lard effects were the decreased insulin (–9.14%) and increased glucagon (+40.44%) and leptin (+44.92%) levels. Relative to St, all diets increased the operational taxonomic units of the phylum Bacteroidetes. G and L decreased, while F increased the proportion of Firmicutes. F and L diets decreased the proportions of Actinobacteria, Proteobacteria and Verrucomicrobia. Correlation and centrality analyses were conducted to ascertain the positive and negative correlations and relative weights of the 32 parameters studied in the metabolic network. These correlations and the underlying potential mechanisms are discussed.

Methylglyoxal Decoration of Glutenin during Heat Processing Could Alleviate the Resulting Allergic Reaction in Mice

Background: It is widely believed that Maillard reactions could affect the sensitization of allergens. However, the mechanism of action of methylglyoxal (MGO) production in Maillard reactions in the sensitization variation of glutenin (a predominant allergen in wheat) during heat processing is still unclear. Methods: This research evaluated the effect of MGO on the immune response against glutenin in a mouse model. The resulting variations in conformation and corresponding digestibility of glutenin were determined. The immune response and gut microflora variation in mice were analyzed following administering of glutenin and MGO-glutenin. Results: The results of the study showed that MGO-glutenin induced a lower immune response than native glutenin. Cytokine analysis showed that MGO-glutenin regulated mouse immune response by inducing Treg differentiation. MGO decoration changed the structure and digestibility of glutenin. In addition, MGO-glutenin contributes to the maintenance of the beneficial gut microflora. Conclusion: MGO decoration of glutenin during heat processing could alleviate the resulting allergic reaction in mice. Decoration with MGO appears to contribute to the aggregation of glutenin, potentially masking surface epitopes and abating sensitization. Furthermore, Bacteroides induced regulatory T-cell (Treg) differentiation, which may contribute to inhibition of the Th2 immune response and stimulation of immune tolerance.

Carrier-Induced Hyporesponsiveness to Pneumococcal Conjugate Vaccines: Unraveling the Influence of Serotypes, Timing, and Previous Vaccine Dose

Background Pneumococcal conjugate vaccines (PCVs) elicit lower immune response against serotypes carried before or at the time of vaccination (hyporesponsiveness) in infants. The limited studies conducted to date did not permit comprehensive insights regarding this phenomenon. This study, the largest ever conducted with both carriage and serologic endpoints, attempted to add insight on serotype-specific hyporesponsiveness in relation to the number of PCV doses administered before carriage acquisition. Methods In a double-blind randomized clinical trial (n = 1754 infants), 7-valent or 13-valent PCV was administered at ages 2, 4, 6, and 12 months. New acquisition was defined based on nasopharyngeal swabs at ages 2, 4, 6, 7, and 12 months. Serotype-specific immunoglobulin G levels were obtained 1 month after the infant series and 1 month after the toddler dose. Results A lower immune response after the infant series and the toddler dose was consistently observed for carriers of serotypes 6A, 6B, 18C, and 19F at predefined time points, with a similar trend observed in carriers of serotype 23F. In contrast, carriage of serotypes 9V, 14, and 19A did not generally affect immune responses. For some but not all serotypes, hyporesponsiveness was decreased with an increased number of vaccine doses received before acquisition. A complex interrelationship between carriage and immune response was observed between cross-reacting serotypes. Conclusions Carrier-induced hyporesponsiveness to PCVs is common, differs among serotypes, and depends on timing of carriage acquisition and prior number of administered PCV doses. Clinical Trials Registration NCT00508742.

2709. Immune Response After Diphtheria and Tetanus Toxoid Booster in Patients with Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibody

Background Immunization were the key of prevention in tetanus and diphtherial disease. Nevertheless, in previous observational study, low seroprotection rate of both diphtheria and tetanus were observed in Thai healthy population. Reduced-dose diphtheria and tetanus toxoid vaccine (dT) was recommended to all adult patients regardless of immunologic status. However, data on vaccine efficacy in interferon gamma (IFN-γ) autoantibody were limited. We therefore conducted clinical study to evaluate efficacy and safety of one dose of dT in IFN-γ autoantibody patient compared with healthy individuals at 4 weeks after vaccination. Methods Study was conducted from February to April 2019. Total 18 patients with confirmed IFN-γ autoantibody were enrolled. Baseline tetanus and diphtheria serologic study and 4 weeks after vaccination were examined. Antibody levels were measured with a solid-phase IgG-specific ELISAs (EUROIMMUN, Germany). Geometric mean titers (GMTs) were calculated using the log transformation of serological titers and from taking the antilog mean of the transformed values. Results Seroprevalence of tetanus was 94.5% in healthy population compared with 60.1% in IFN-γ autoantibody patients. While, seroprevalence of diphtheria was 27.8% and 77.8%, respectively. After vaccination, all healthy adults had reached seroprotection level in both diphtheria and tetanus. For patients with IFN-γ autoantibody, 88.9% and 94.4% had anti-tetanus toxin IgG and anti-diphtheria toxin IgG level above 0.1 IU/mL, respectively. These results indicated seroconversion rate of 71% for tetanus and 75% for diphtheria after dT vaccination. (Table 2). In the subgroup analysis, unboosted IFN-γ autoantibody patient had lower tetanus seroconversion rate compared with previously boosted patient (50% vs 100%). Active infection was also associated with lower immune response after tetanus vaccination. There was no severe adverse event in both group. Conclusion This is the first study on immune response after dT vaccination in IFN-γ autoantibody patient. Seroconversion rate of dT vaccine in IFN-γ autoantibody patient were slightly lower than healthy adults. Active infection and previously unboosted patient provided lower immune response of tetanus. Disclosures All authors: No reported disclosures.

An investigation of the efficacy on hepatitis B vaccination in hemodialysis patients in Ardabil, Iran

Introduction: Hemodialysis patients usually demonstrate lower immune response to hepatitis B vaccine compared to non-uremic population. Objectives: The present study aimed to determine the level of response to hepatitis B vaccination in patients under hemodialysis. Patients and Methods: This study was conducted on 172 live patients receiving hemodialysis in the dialysis department of Buali hospital in Ardabil, Iran (2015). To analyze their response to the vaccine, their vaccination titers were investigated. Before vaccination, the serological markers of hepatitis B and C were checked in all of the patients. Those for whom HBsAg and HBsAb results were negative and had not received the vaccinein the past entered the study. The patients received a double dose of hepatitis B vaccine at 0, 1, and 6 months after the beginning of dialysis. The response to the vaccine was investigated by measuring the level of patients’ hepatitis B antibody one month after receiving the last dose of the vaccine. Results: Seventy patients (40% of the total) displayed a proper immune response to the vaccine, 34 patients (19.8%) were without, and 68 patients (39.5%) were identified to have poor response. The results of Pearson’s correlation test indicated that there is a negative correlation between the patients’ age and their response to the vaccine. Conclusion: The results of this study indicated that higher age is one of the factors that reduce the effectiveness of hepatitis B vaccine in hemodialysis patients.