Abstract LB-250: The alteration of the colonic microbial community and metabolomic profile in humans: Results from a 90-day double-blinded, randomized interventional trial

Abstract

Introduction: The bacteria making up the microbial community of the gastrointestinal tract, by virtue of their ability to produce pro-carcinogenic bile acids and anti-carcinogenic short chain fatty acids (SCFA), are thought to influence the colonic health. Methods: Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day double-blinded, randomized interventional trial in which Aquamin, a calcium- and magnesium-rich, multi-mineral product was compared to calcium alone and placebo for effects on the colonic microbial community and metabolomic profile. Aquamin and calcium (carbonate) alone groups provided 800 mg of calcium per day from the respective sources. Colonic tissue and stool samples were obtained endoscopically from unpreped sigmoid colon with a flexible sigmoidoscope before and after the intervention and were subjected to microbial and metabolomic analysis. Illumina® MiSeq sequencing of the V4 region of 16S rRNA genes was used to assess the bacterial populations represented in both colon mucosal biopsies and fecal material and qPCR was used to obtain an estimate of total bacterial DNA in each tissue and stool specimen. In parallel, a 2-step extraction procedure followed by liquid chromatography-mass spectrometry was used to assess bile acids and SCFA. Results: As far as safety and tolerability is concerned, there were no serious adverse events to report during the trial with Aquamin or calcium. Compared to pretreatment values from both colonic biopsies and stool specimens, intervention with Aquamin led to a reduction in total bacterial load (based on qPCR). Treatment with calcium alone produced intermediary changes in total bacterial DNA while no reduction was observed with placebo. Based on sequencing of the V4 region of 16S rRNA genes, there were significant pre-post differences, but intra-subject variability was less than the variability between individuals. In spite of the high variability, greater pre-post interventional differences were seen with Aquamin relative to calcium alone and placebo. Differences between Aquamin and calcium alone reached statistical significance. Several operational taxonomic units representing major microbial phyla present in the colon (i.e., actinobacteria, bacteroidetes, and firmicutes) were reduced in response to Aquamin compared to placebo. Reductions were also seen with calcium but these were intermediary between Aquamin and placebo. In parallel with microbial changes, we observed a reduction in total bile acid levels and an increase in the level of acetate (an SCFA) in stool specimens from Aquamin-treated subjects. No or minimal change in bile acids or SCFAs was observed with calcium alone or placebo. Some of the primary bile acids (cholate and Chenodeoxycholate/deoxycholate) and the secondary bile acids (alpha-Murocholate, hyocholate, hyodeoxycholate, and omega-Muricholate) were significantly reduced with Aquamin. Additionally, on eicosanoids assessment in colon biopsies, 13S-HODE was reduced with Aquamin. Conclusion: The combination of calcium, magnesium and additional trace elements (as present in Aquamin) can produce alterations in the colonic microbial community and the attendant metabolomic profile that could be beneficial to colonic health in subjects at risk for colorectal cancer. Citation Format: Muhammad N. Aslam, Christine Bassis, Ingrid Bergin, Karsten Knuver, Ananda Sen, Danielle Kim Turgeon, James Varani. The alteration of the colonic microbial community and metabolomic profile in humans: Results from a 90-day double-blinded, randomized interventional trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-250.