The effect of prebiotic supplementation with inulin on cardiometabolic health: Rationale, design, and methods of a controlled feeding efficacy trial in adults at risk of type 2 diabetes

Abstract

Prediabetes is associated with low-grade chronic inflammation that increases the risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). An elevated lipopolysaccharide concentration, associated with dysbiosis of the intestinal microbiota, has been implicated in the development of both T2D and CVD. Selective modulation of the intestinal microbiota with prebiotics reduces intestinal permeability and endotoxin concentrations, inflammation, and metabolic dysfunction in rodents. The effect of prebiotic supplementation on cardio-metabolic function in those at risk for T2D is not known. The primary aim of this trial is to determine the influence of prebiotic supplementation with inulin on insulin sensitivity and skeletal muscle metabolic flexibility in adults at risk for T2D. We hypothesize that prebiotic supplementation with inulin will improve insulin sensitivity and skeletal muscle metabolic flexibility. We will randomize 48 adults (40–75 yrs) with prediabetes or a score ≥5 on the American Diabetes Association (ADA) risk screener to 6 weeks of prebiotic supplementation with inulin (10 g/day) or placebo. Subjects will be provided with all food for the duration of the study, to avoid potential confounding through differences in dietary intake between individuals. Intestinal permeability, serum endotoxin concentrations, insulin sensitivity, skeletal muscle metabolic flexibility, endothelial function, arterial stiffness, and fecal bacterial composition will be measured at baseline and following treatment. The identification of prebiotic supplementation with inulin as an efficacious strategy for reducing cardio-metabolic risk in individuals at risk of T2M could impact clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.

Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans

“…Four sugar probes were employed to assess gut permeability [22] as described previously [23,24], assessing permeability in all regions of the gut (see Table 1). Urine was collected in two pooled samples: a 0-5 h sample representative of gastric and small intestinal permeability (collected during the visit), and a 6-24 h sample representative of colonic permeability (collected after the visit) [25,26].…”

“…Urine was collected in 24 h collection containers with 5 mL 10% thymol in methanol (w/v) to inhibit bacterial growth. Excretion (quantified by UPLC-MS/MS) was calculated as a percentage of total sugar dose recovered as described previously [23]. Data acquisition, processing, and quantification of the sugar probe data was performed using Waters MassLynx v4.1 software.…”

Therapeutic Potential of Probiotics and Prebiotics

“…The prebiotic supplementation along with inulin could be used as preventive strategy for limiting the risk of cardiovascular diseases in the patients at risk of type 2 diabetes. This strategy can affect the clinical practices by setting and accepting dietary recommendation of prebiotics by medical and scientific community [126].…”

Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

“…In clinic, prebiotics have also been trialed for their benefits in various diseases [127][128][129][130][131]. Oligofructose (OFS), an inulin-type fructans, were added to diet for patients with NASH in a pilot randomized double-blind study [118].…”