Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial

Abstract

Context: The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals.

Objective: We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population.

Methods: Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB a mean 5 years prior; a 2-month course of 20 g/day SCF or maltodextrin placebo was taken orally. The main outcome measure was between-group difference in absolute change in FCA (primary outcome) and was measured with a gold standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing.

Results: Mean FCA ± SD at baseline was low at 5.5 ± 5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7, +13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r2 = 0.72, P = 0.05). SCF adherence was high, and gastrointestinal symptoms were similar between groups.

Conclusion: No between-group differences were observed in changes in FCA or calciotropic hormones, but wide CIs suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well tolerated. Larger and longer-term studies are warranted.

Trial registration: ClinicalTrials.gov NCT03272542.

Keywords: bariatric surgery; calcium absorption; gastric bypass; obesity; prebiotic.

Figure 1.

Study flow diagram.

Figure 2.

Fractional calcium absorption before and at end of intervention by treatment group. (A) FCA over 24 hours (%) after dual-isotope administration. (B) FCA over 48 hours (%) after dual-isotope administration.

Figure 3.

Exploratory gut microbiome outcomes. (A) α-Diversity (within sample microbial diversity) between treatment groups at end of intervention with Shannon diversity index, phylogenetic diversity, richness, and evenness measures. (B) β-Diversity (between-sample compositional dissimilarity) with weighted UniFrac, unweighted UniFrac, Bray–Curtis, and Canberra. (C) Shift in microbial community composition pre–post intervention between treatment groups with Bray–Curtis dissimilarity measure (ordination axes 1 and 2 shown here). The P values were derived from Wilcoxon signed-rank test, indicating whether each β-diversity ordination axis differed from baseline to follow-up within each randomization group. Linear mixed-effects interaction analysis of variance P values were derived from a linear mixed-effects model and two-way analysis of variance test, indicating whether the shift in β-diversity across baseline and follow-up differed between the prebiotic and placebo groups (ie, β-diversity ordination axis as a function of randomization group and timepoints). (D) Significantly different taxa relative abundance pre–post intervention in prebiotic group, pre–post intervention in placebo group, and between treatment groups (prebiotic vs placebo) at end of intervention.