Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial

Abstract

Background: The gut microbiota is interlinked with obesity, but direct evidence of effects of its modulation on body fat mass is still scarce. We investigated the possible effects of Bifidobacterium animalisssp. lactis 420 (B420) and the dietary fiber Litesse® Ultra polydextrose (LU) on body fat mass and other obesity-related parameters.

Methods: 225 healthy volunteers (healthy, BMI 28-34.9) were randomized into four groups (1:1:1:1), using a computer-generated sequence, for 6months of double-blind, parallel treatment: 1) Placebo, microcrystalline cellulose, 12g/d; 2) LU, 12g/d; 3) B420, 10¹⁰CFU/d in microcrystalline cellulose, 12g/d; 4) LU+B420, 12g+10¹⁰CFU/d. Body composition was monitored with dual-energy X-ray absorptiometry, and the primary outcome was relative change in body fat mass, comparing treatment groups to Placebo. Other outcomes included anthropometric measurements, food intake and blood and fecal biomarkers. The study was registered in Clinicaltrials.gov (NCT01978691).

Findings: There were marked differences in the results of the Intention-To-Treat (ITT; n=209) and Per Protocol (PP; n=134) study populations. The PP analysis included only those participants who completed the intervention with >80% product compliance and no antibiotic use. In addition, three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement. There were no significant differences between groups in body fat mass in the ITT population. However, LU+B420 and B420 seemed to improve weight management in the PP population. For relative change in body fat mass, LU+B420 showed a-4.5% (-1.4kg, P=0.02, N=37) difference to the Placebo group, whereas LU (+0.3%, P=1.00, N=35) and B420 (-3.0%, P=0.28, N=24) alone had no effect (overall ANOVA P=0.095, Placebo N=35). A post-hoc factorial analysis was significant for B420 (-4.0%, P=0.002 vs. Placebo). Changes in fat mass were most pronounced in the abdominal region, and were reflected by similar changes in waist circumference. B420 and LU+B420 also significantly reduced energy intake compared to Placebo. Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU+B420 group and in the overall population. There were no differences between groups in the incidence of adverse events.

Discussion: This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU+B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.

Keywords: Clinical trial; Fiber; Obesity; Prebiotic; Probiotic; Synbiotic.

Fig. 1

Participant flow. Before unblinding the study, participants were divided into an Intention-to-Treat (ITT) population and a Per Protocol (PP) population according to adherence to the study protocol.

Fig. 2

Weight management outcomes. Change in total body fat mass from baseline to end of study (6 months of intervention) in the Intention-to-Treat (a) and Per Protocol (PP) (b) populations. Evolution of body fat mass in the PP population during intervention and at follow-up (c). Changes in trunk fat mass (d), android fat mass (e), lean body mass (f), body weight (g), waist circumference (h) and hip circumference (i) from baseline to end of study in the PP population. Body composition in panels a-f was measured with dual-energy X-ray absorptiometry. Results are expressed as mean ± 95% CI. Results were analyzed with ANCOVA and Dunnett's pairwise comparisons corrected for multiple testing. In the ITT population, the last observation was carried forward for the statistical analysis of participants who withdrew from the study. Solid line shows baseline; dotted line shows the level of the Placebo group. N of participants included in the statistical analysis in the Intention-to-Treat population: Placebo n = 53, LU n = 51, B420 n = 47, LU + B420 n = 48. N for the PP population: Placebo n = 35–36, LU n = 35–36, B420 n = 24–25, LU + B420 n = 37. Overall ANCOVA as follows: a) P = 0.46, b) P = 0.095, d) P = 0.036, e) P = 0.23, f) P = 0.30, g) P = 0.13, h) P = 0.10, i) P = 0.31.

Fig. 3

Correlation between serum zonulin, serum hsCRP and trunk fat mass. Evolution of zonulin (a) and hsCRP (c), and correlations between zonulin (b) and hsCRP (d) with trunk fat mass as changes from baseline to end-of-intervention (6 months) in the Per Protocol population. Panels a) and c) display changes from baseline as mean ± 95% confidence intervals at each time point. Placebo n = 35–36, LU n = 35–36, B420 n = 24–25, LU + B420 n = 36–37.