The goal is to establish the effect of oral probiotic Desulfovibrio piger (D. piger) supplementation on immunological and metabolic parameters in individuals with longstanding type 1 diabetes with residual beta cell function. The investigators will perform a double-blind, randomized, placebo-controlled trial in 2x10 participants to measure effects of D. piger on parameters of systemic and intestinal inflammation and residual beta cell function.
Males or females, age >18 years
A diagnosis of type 1 diabetes, with duration of more than 5 years, with minimally one of antiGAD65, IA2, ZnT8 autoantibodies present assessed at diagnosis or routine visits at Diabeter Centrum.
Evidence of remaining residual beta cell function with detectable UCPCR (more than 0.01 nmol/mmol C-peptide/creatinine ratio) and or fasting plasma C-peptide more than 0.2 mmol/L.
BMI 18-30 kg/m2
Use of antibiotics or proton-pump inhibitors within the last three months before screening or during study period
Use of other probiotic supplementation within the last month before screening or during study period
A history of cholecystectomy
Overt untreated gastrointestinal disease, inflammatory bowel disease or abnormal bowel habits
Parallel
Probiotic dietary supplement
Dietary supplementProbiotic bacteria D. piger (10\^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
Placebo
Dietary supplementPlacebo (10ml PBS containing 10% glycerol and 10% maltodextrin)
Parameters of systemic and intestinal inflammation
systemic inflammation determined by measuring plasma CRP, and proinflammatory cytokines (IFNgamma, IFN alpha, TNFalpha) intestinal inflammation assessed by LB, iFABP, zonulin in plasma
Residual beta cell function
Assessed by C peptide AUC during mixed meal tolerance test and/or post meal urine C-peptide/creatinine ratio levels.
Glucose variability
percentage time in euglycemic range, time above range, time below range and glucose variability measured by continuous glucose monitoring (CGM)
Immune cell phenotypes and frequency
Immunophenotyping by flow cytometry of PBMC (peripheral blood mononuclear cells) to determine frequency of T cell subsets with activation/exhaustion marker expression
Fecal microbiome composition and strain engraftment
using 16s rRNA sequencing, primer-specific quantitative PCR for D. piger detection in feces and plasma metabolites
Gastrointestinal Symptom Rating Scale (GSRS)
Questionnaire. The minimum and maximum score are 15 and 105 points respectively, and a higher score in the scale reflects more gastro-intestinal complaints.
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