Feasibility Study Examining the Association between Gut Microbiota and Immune Response to Seasonal Influenza Vaccination in Healthy Adults

Gut Microbiota ◽

Study Protocol ◽

Controlled Trial ◽

Host Immune Response ◽

Blood Samples ◽

Community Types ◽

Stool Samples ◽

<p>Research into the effect of the gut microbiota on host immune response is continuing to shed new light on the underappreciated role of the microbiota in human health. Recent research using mice has shown that the microbiota is critical to the host immune response to influenza infection. Whilst there is great variation in the human gut microbiota, classifications called stool community types can be used to classify individuals based on the abundance of major bacterial taxa. The primary objective of this study was to investigate the feasibility of using the study protocol for a large randomised controlled trial. Healthy adult participants (n=125) aged 18 to 64 were recruited from the general population and vaccinated with the seasonal trivalent influenza vaccine. Participants were followed up over a period of six months, during which time, both stool and blood samples were collected. Blood samples were collected at Day Zero, Three, Seven, 28 and 180 to measure immune response. The immune response to vaccination was measured by HAI antibody titres at Day Zero and Day 28. Stool samples were collected at Day Zero and Day 28 to assign participants to one of the four stool community types and assess stability over time. Stool samples were assigned to stool community types using the proportions of major taxa present. The association between stool community type and either post vaccination HAI titre, seroconversion rates or seroprotection rates was also assessed. The results obtained in this study supported the feasibility of a large randomised controlled trial using the study protocol. The study demonstrated a high participant retention rate (97.6%; 95% CI = 93.1% to 99.5%), as well as high participant adherence to the study protocol and good success obtaining the required blood and stool samples.</p>

Modulation of bone/joint biomarkers, gut microbiota and inflammation status by synbiotic (pre- and probiotics) and weight-bearing exercise; human study protocol for a randomised controlled trial COPES (COmbination of Physical Exercise and Synbiotics) 4 Bones (Preprint)

JMIR Research Protocols ◽

10.2196/30131 ◽

2021 ◽

Author(s):

Bolaji Lilian Ilesanmi-Oyelere ◽

Nicole C. Roy ◽

Marlena C. Kruger

Keyword(s):

Physical Exercise ◽

Gut Microbiota ◽

Study Protocol ◽

Controlled Trial ◽

Weight Bearing ◽

Human Study ◽

Design and evaluation of a theory-based intervention of knowledge and perceptions to improve self-care amongst relatives of esophageal cancer patients: A randomised controlled trial study protocol

International Journal of Surgery Protocols ◽

10.1016/j.isjp.2020.09.001 ◽

2020 ◽

Vol 24 ◽

pp. 12-16

Author(s):

Sakineh Gerayllo ◽

Mohammad Ali Morowatisharifabad ◽

Leila Jouybari ◽

Zohreh Karimiankakolaki ◽

Reza Sadeghi

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Study Protocol ◽

Controlled Trial ◽

Self Care ◽

Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial

Diabetologia ◽

10.1007/s00125-020-05376-1 ◽

2021 ◽

Author(s):

Robin Assfalg ◽

Jan Knoop ◽

Kristi L. Hoffman ◽

Markus Pfirrmann ◽

Jose Maria Zapardiel-Gonzalo ◽

...

Keyword(s):

Immune Response ◽

Type 1 Diabetes ◽

Primary Outcome ◽

Controlled Trial ◽

Antibody Responses ◽

Oral Insulin ◽

Cell Responses ◽

Abstract Aims/hypothesis Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome. Methods A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory. Results Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes. Conclusions/interpretation The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells. Trial registration Clinicaltrials.gov NCT02547519 Funding The main funding source was the German Center for Diabetes Research (DZD e.V.) Graphical abstract