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Title:   Author  item
                                            RUST, BRET - University Of Californiaitem
                                            LA FRANO, MICHAEL - University Of Californiaitem
                                            Newman, Johnitem
                                            AGRAWAL, KARAN - University Of Californiaitem
                                            Horn, Williamitem
                                            WELCH, LUCAS - University Of Californiaitem
                                            MARCO, MARIA - University Of Californiaitem
                                            MARTIN, ROY - University Of Californiaitem
                                            Keim, Nancy
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 12/8/2015
                                    Publication  Date: 4/2/2016
                                    Citation: Rust, B., La Frano, M., Newman, J.W., Agrawal, K., Horn, W.F., Welch, L., Marco, M., Martin, R., Keim, N.L. 2016. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals. Meeting Abstract. Experimental Biology 2016, San Diego, CA April 2-6, 2016.Interpretive Summary:
                                Technical Abstract: Bile acids and their conjugates are important regulators of glucose homeostasis. Previous research has revealed the ratio of cholic acid to deoxycholic acid to affect insulin resistance in humans.  Bile acid de-conjugation and intestinal metabolism depend on gut microbes which may be affected by host diet. Gut microbes and host diet may alter energy availability and microbial diversity thus affecting glucose homeostasis. Methanogenic bacteria are abundant in some individuals.  Potential microbial community differences in methane producers may result in differential substrate metabolism, and we hypothesize that this will affect levels of primary, secondary and tertiary bile acids and their conjugates. We intended to discover the relationship between consumption of a polysaccharide in methane producers and non-producers to the response in plasma bile acids after a test meal.  Twenty-two men and women with low reported dietary fiber intake consumed either zero, 15 or 30 grams of a 10-12 monomer fructo-oligosaccharide terminated by a maltose moiety for three weeks in a randomized crossover trial. After each three week intervention participants underwent a test day protocol in which half their daily dose of added fiber was consumed with breakfast. Feces were collected for five days prior to the test day. Breath hydrogen and methane were collected and fasting and post-prandial blood draws were performed on the test day. Subjects were characterized from breath gas and fecal microbial 16s RNA analysis as either methane producers (MP) or non-producers (NP). To isolate bile acids, organic solvent and deuterium labeled internal standards were added to plasma and eluted through a 96 well phospholipid removal plate. Bile acids were measured using UPLC-MS/MS at fasting and four subsequent post prandial time points over 195 minutes. Glucose and insulin responses were measured following the test meal. We compared responses to the treatment in 15 primary, secondary and tertiary conjugated and unconjugated plasma bile acids.  Multivariate partial least squares analysis was used to discriminate potential treatment effects and at each time point following the test meal.  The level of polysaccharide consumption did not affect bile acid concentrations. Twelve bile acids, 3 primary bile acids and 9 secondary bile acid species had lower AUCs in MP than in NP (p<0.05). No differences were observed in cholic acid and deoxycholic acid. Glucose AUCs were significantly lower in MP than NP (p<0.05) but insulin responses were not. Differences between glucose responses in MP may be related to differential bile acid responses and their regulation of glucose metabolism in the liver.


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