A microbiome-targeting fibre-enriched nutritional formula is well tolerated and improves quality of life and haemoglobin A1c in type 2 diabetes: A double-blind, randomized, placebo-controlled trial.

AIMS: To investigate a prebiotic fibre-enriched nutritional formula on health-related quality of life and metabolic control in type 2 diabetes. MATERIALS AND METHODS: This was a 12-week, double-blind, placebo-controlled study with an unblinded dietary advice only comparator arm. Participants were randomized 2:1:1 to a prebiotic fibre-enriched nutritional formula (Active), a placebo fibre-absent nutritional formula (Placebo), or non-blinded dietary advice alone (Diet). Primary endpoint was change in core Type 2 Diabetes Distress Assessment System (cT2-DDAS) at week 12. Glycated haemoglobin (HbA1c) change was a key secondary endpoint. RESULTS: In total, 192 participants were randomized. Mean age was 54.3 years, HbA1c 7.8%, and body mass index 35.9 kg/m2 . At week 12, cT2-DDAS reduced significantly in Active versus Placebo (-0.4, p = .03), and HbA1c was reduced significantly in Active vs Placebo (-0.64%, p = .01). Gut microbiome sequencing revealed that the relative abundance of two species of butyrate-producing bacteria (Roseburia faecis and Anaerostipes hadrus) increased significantly in Active vs. Placebo. CONCLUSIONS: A microbiome-targeting nutritional formula significantly improved cT2-DDAS and HbA1c, suggesting the potential for prebiotic fibre as a complement to lifestyle and/or pharmaceutical interventions for managing type 2 diabetes.

The impact of loss of myrosinase on the bioactivity of broccoli products in F344 rats.

In vitro, animal, and epidemiological studies all show that broccoli products containing sulforaphane, the bioactive hydrolysis product of glucoraphanin (GRP), lower risk for cancer. As a result, GRP-rich extracts are appearing on the market as dietary supplements. However, these products typically have no hydrolyzing enzyme for sulforaphane (SF) formation. We evaluated safety and compared efficacy to other broccoli preparations. Four daily doses of 0.5 mmol GRP/kg BW, given by gavage to adult male F344 rats, caused temporary cecal inflammation that was essentially resolved four days later. A similar dose dispersed in the diet caused no inflammation. To compare efficacy, we fed rats 20% freeze-dried broccoli (heated or unheated), 3.5% broccoli seed meal, or 4.3% semipurified GRP, each balanced within an AIN93G semipurified diet, for 4 days. Diets lacking myrosinase (semipurified GRP and heated broccoli florets) caused upregulation of NAD(P)H-quinone oxidoreductase 1 (NQO1) in colon but not liver. Surprisingly, broccoli seed, rich in myrosinase and GRP, also caused NQO1 upregulation in colon but not liver. In contrast, unheated broccoli florets caused upregulation in both colon and liver. These data suggest that GRP supplements may not exert systemic effects. We hypothesize that within whole broccoli additional components enhanced sulforaphane-dependent upregulation of NQO1 in liver.

Glucoraphanin hydrolysis by microbiota in the rat cecum results in sulforaphane absorption.

In the absence of the plant enzyme myrosinase, such as in cooked broccoli, glucoraphanin is considered to be hydrolyzed by bacteria in the lower gut to produce the bioactive isothiocyanate sulforaphane. Simulated digestion using US Pharmacopeia methods caused no loss of glucoraphanin, confirming that glucoraphanin is not destroyed by digestive enzymes during passage through the digestive tract and is able to reach the rat cecum intact. Introduction of glucoraphanin (150 µmol/kg BW) directly into the cecum resulted in appearance of isothiocyanates in the mesenteric plasma by 120 min. In contrast, introduction of sulforaphane (150 µmol/kg BW) directly into the cecum resulted in the appearance of isothiocyanates in the mesenteric plasma within 15 min. Plasma levels remained constant for over an hour. Anaerobic incubation ex vivo of cecal microbiota from male F344 rats with glucoraphanin resulted in very low levels of the hydrolytic metabolite erucin nitrile, showing that hydrolysis of glucosinolates is carried out by cecal microbiota, but metabolism ex vivo by microbiota did not reflect not reflect metabolism in situ. These data are the first to report direct evidence of hydrolysis of glucoraphanin to sulforaphane in the cecum of rats and to show that sulforaphane is able to cross the cecal enterocyte for systemic absorption.