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Title:   Author  item
                                            COOPER, DANIELLE - University Of Californiaitem
                                            KIM, EUN BAE - Seoul National Universityitem
                                            MARCO, MARIA - University Of Californiaitem
                                            RUST, BRETT - University Of Californiaitem
                                            WELCH, LUCAS - University Of Californiaitem
                                            Horn, Williamitem
                                            Freytag, Tammyitem
                                            MARTIN, ROY - University Of Californiaitem
                                            Keim, Nancy
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 11/9/2015
                                    Publication  Date: 4/2/2016
                                    Citation: Cooper, D., Kim, E., Marco, M., Rust, B., Welch, L., Horn, W.F., Freytag, T.L., Martin, R., Keim, N.L. 2016. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults. Meeting Abstract. Experimental Biology 2016, April 2-6, 2016, San Diego, CA..Interpretive Summary:
                                Technical Abstract: Background: Gut microbial diversity and abundance can profoundly impact human health. 
Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and inflammation is unclear. IL-6 is a pro-inflammatory cytokine that has been linked to disease states such as diabetes and obesity when chronically elevated.  Establishing a relationship between IL-6 and microbial abundance or diversity could improve diagnostics assessment or create new avenues for clinical treatment. Methods: Twenty-two human subjects were recruited to participate in a fermentability study of a novel fiber. The study utilized a crossover design with a baseline period and three arms that lasted three weeks, each arm was separated from the next arm by a two week washout period. During the baseline and two washout periods subjects ate their usual diet and collected a single fecal sample. During the third week of each of the three arms subjects consumed a low fiber controlled diet and either no, or a high or low dose of the novel fermentable fiber. Also in the third week subjects collected all fecal samples and participated in a test day where blood was repeatedly drawn. Bacterial genomic DNA was extracted from the pooled week of fecal samples. Microbial diversity and relative abundance were determined based on sequencing the bacterial 16S rRNA. Assays of blood drawn on the test days were utilized to determine IL-6 concentration. R was used to assess the relationship between IL-6 and microbial abundance. Results: Principle Component Analysis as well as other statistical tests confirmed that no strong treatment effects were observed between the no, low, and high fiber arms. IL-6 data from each arm’s test day were averaged across the day and ranged from 1.75pg/mL to 32.03pg/mL. Subjects with a concentration greater than 20pg/mL (mean 27.21± 3.17), were considered to have a higher concentration of IL-6 whereas subjects with less than 20pg/mL (mean 8.89 ± 4.29) were considered to have a lower concentration of IL-6. Least Partial Square Regression showed clear separation between the microbiota of subjects with higher verses lower concentrations of IL-6. Further testing elucidated that this separation was driven by significant (p = 0.04759) enrichment of Lactobacillus coryniformi, Lactobacillus helveticus, and Lactobacillus ruminis in the higher IL-6 producers. Conclusion: This study demonstrates an increased abundance of  Lactobacillus species in overweight and obese subjects with higher concentrations of circulating IL-6. The relationship described between Lactobacillus and IL-6 is surprising and requires further investigation. A limitation of this study is that it is not able to establish a causal factor so it remains unknown whether it is the IL-6 level that shapes the microbial community or if it is the resident microbes that influence IL-6 concentrations. Future research is needed to determine the exact nature of the relationship between IL-6 and gut microbiota.


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