Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.

BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters. CONCLUSIONS: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566).

Feasibility of a bihormonal closed-loop system to control postexercise and postprandial glucose excursions.

BACKGROUND: The aim of this pilot study was to test the feasibility of a bihormonal (glucagon and insulin) closed-loop (CL) system by challenging the system with two meals and 30 min exercise. METHODS: Ten patients with type 1 diabetes treated with continuous subcutaneous insulin infusion underwent a standardized protocol on three different occasions: 40 g carbohydrate breakfast followed 2 h later by 30 min of moderate-intensity exercise, followed 1.5 h later by a standardized 60 g carbohydrate lunch. An open-loop (OL) day served as control, the first CL day as tuning experiment, and the second CL day to compare with OL. RESULTS: The overall mean venous glucose was similar: 9 (5.4-13.5) mmol/liter in OL versus 8.7 (6.4-11.0) mmol/liter in CL, p = .74. The postbreakfast glucose concentrations tended to be lower in OL than in CL [9.5 (4.3-13.3) versus 11.4 (7-16.2) mmol/liter; p = .07] and higher in OL than in CL postlunch [9.4 (6.0-14.9) versus 7.7 (5.5-9.0) mmol/liter,p = .15]. The postexercise glucose concentrations were similar in OL and CL: 7.5 (4.6-13) versus 8.2 (5.5-13.1) mmol/liter; p = .45. In those patients coming in with baseline glucose above 7 mmol/liter, there was initial overinsulinization in CL. During OL, two hypoglycemic episodes occurred compared with four hypoglycemic episodes in three participants during CL. Glucagon seemed mostly effective in preventing hypoglycemia. CONCLUSIONS: Overall, CL glucose control was comparable to OL control, but there was overinsulinization in those patients with baseline glucose above 7 mmol/liter.