Progress 03/01/12 to 12/31/16
Outputs
Target Audience:The research we are conducting as part of this project should be of interest to researchers and clinicians who study obesity, gut health, and the role of the gut microbiota on obesity and other health conditions. In addition, this research should be of interest to public health officials and scientists who work on obesity-related diseases, especially gut barrier function disorders. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The students and staff working on this project gained invaluable experience in several areas, including clincial study design and implementation, assessment of diseases biomarkers, microbiota analysis, and bioinformatics. Students also participated in professional international conferences and were given opportunities to collaborate with other professionals from academic and medical discliplines. How have the results been disseminated to communities of interest?Results have been described in two high impact publication, as well as at several conferences. There has already been considerable attention and when the main results are published later this year, we expect even more interest. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We conducted a double-blinded, randomized, placebo-controlled human clincial study. There were 5 treatment groups and 1 placebo. A total of 105 subjects (BMI > 30) completed the study, with 19 subjects in the placebo group, 17 in the IVS-1 strain group, 16 in the Bb12 strain group, 17 in IVS-1 + the prebiotic GOS, 19 in Bb12 + GOS, and 17 in the GOS group. Accomplishments (per goal) were as follows. (1) Administration of IVS-1, Bb12, or GOS resulted in very specific changes in strain abundance, with few other changes in OTUs and limited impact on the overall composition of the gut microbiota. Only one phylum was significantly influenced by the dietary treatments, as the relative proportion of Actinobacteria was significantly higher in subjects treated with IVS-1. At the genus level, the relative abundance of Bifidobacterium was increased only in group IVS-1. GOS also increased relative abundance of Bifidobacterium, but this increase was not statistically significant. In contrast, most changes were detected at the OTU or species level, with sequencesidentical to the probiotic strain B. adolescentis IVS-1 and B. lactis subsp. animalis Bb 12 enriched in the respective synbiotic treatments. In adiditon, an analysis of the Prevotella and Bacteroides ratio in this study showed no significant difference within a treatment group, or when groups were compared. Additionally, the abundance of butyrate producing genera such as Faecalibacterium, Eubacterium, Roseburia, Lachnobacterium, and Ruminococcus was not significantly influenced by any of the treatments, nor was their combined abundance changed by any of the treatments. The alpha and beta diversity was compared between all three time points within each group, and across all six groups for all three time points. No differences existed in alpha and beta diversity for any of the comparisons. (2) Probiotic strains can be established in the gastointesitnal tract and this effect is enhanced by GOS. When compared to the baseline and washout samples, both tests strains reached significantly higher total cell numbers in the presence as well as absence of GOS. However, IVS-1 colonized the GI tract at a significantly higher number than Bb12 in the probiotic only treatments and when GOS was added. This suggests that the autochthonous strain IVS-1 had an ecological advantage over the allochthonous commercial strain Bb12 and confirmed our ecological strategy. (3) This study confirmed that GOS and Bifidobacterium treatments can have beneficial effects on gastrointestinal permeability in obese human subjects (depending on the specifc sugars used in the permeability measurements). Specifically, the treatments containing IVS-1, IVS-1 in combination with GOS, and GOS alone improved primary colonic permeability. Similarly, Bb12 probiotic treatment and GOS alone also improved permeability. Interestingly, the combination of Bb12 and GOS did not significantly improve permeability. Nonetheless, this finding demonstrated that this allochthonous strain can be beneficial under specific circumstances. As intestinal permeability may influence host metabolism, changes in anthropometrics and metabolic markers of chronic disease were assessed. Minimal changes were seen in both anthropometrics and metabolic markers, nor were severe adverse GI symptoms reported. (4) Correlation analyses revealed that several, mostly Gram positive, taxa were correlated with improved gut permeability measurements. These included taxa that have previously been associated with improved gastrointestinal permeability such as Anaerostipes, Lachnospiraceae incertae sedis, Ruminococcus, Collinsella, Alistipes, Actinomyces, Blautia, and Dorea. Several of these organisms (family Lachnospiraceae) produce butyrate, which promotes intestinal integrity. Previous reports suggest that high abundance of members of this family beneficially affect GI permeability in pigs, and human studies have shown that low abundances are associated with increased colonic permeability and endotoxemia. Collectively this study provided further insight into the associations between microbes and markers of intestinal permeability in the context of obesity in human subjects.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Krumbeck, J.A., M.X. Maldonado-Gomez, I. Mart�nez, S.A. Frese, T.E. Burkey, K. Rasineni, A.E. Ramer-Tait, E.N. Harris, R.W. Hutkins, and J. Walter. 2015. In vivo selection to identify bacterial strains with enhanced ecological performance in synbiotic applications. Appl. Environ. Microbiol. 81:2445-2465
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Krumbeck, J.A., M.X. Maldonado-Gomez, A.E. Ramer-Tait, and R.W. Hutkins. 2016. Prebiotics and synbiotics - dietary strategies for improving gut health. Curr. Opin. Gastroenterol. 32:110-119.
- Type:
Journal Articles
Status:
Awaiting Publication
Year Published:
2017
Citation:
Krumbeck, J.A., H.E. Rasmussen, R.W. Hutkins, J. Clark, K. Shawron, A. Keshavarzian, and J. Walter. 2017. Comparison of the effect of two synbiotics and their pro- and prebiotic components on intestinal barrier function and the gut microbiota in obese subjects
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Progress 03/01/15 to 02/29/16
Outputs
Target Audience:The target audiences for this research include the following: 1. Scientists conducting research on gut health 2. Scientists conducting reearch on probiotics, prebiotics, and synbiotics 3. Scientists and health professionals conducting research on obesity 4. Pharma and life science professionals interested in gut health products Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate students on this projece received training in clinical microbiology and bioinformatics and in many of the steps necessary to conduct human trials.. How have the results been disseminated to communities of interest?Publication in journals, presentations at conferences What do you plan to do during the next reporting period to accomplish the goals?The remaining analyses will be completed in the next few months, and a manuscript willbe submitted.
Impacts
What was accomplished under these goals?
We have completed our randomized, placebo-controlled, parallel-arm clinical trial that tested the hypothesis that a rationally selected synbiotic will improve intestinal barrier function in obese adults and thereby prevent endotoxemia and metabolic inflammation. A total of 120 subjects complted the study. Biological samples were obtained and analysed. fecal samples were processed and 16s amplicons were sequenced. Sequences have been obtsained and are being anaklyzed. Likewise, blood and urine samples were also obtained and are being analyzed.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
J.A. Krumbeck, M.X. Maldonado-Gomez, I. Mart�nez, S.A. Frese, T.E. Burkey, K. Rasineni, A.E. Ramer-Tait, E.N. Harris, R.W. Hutkins, J. Walter. 2015. In vivo selection to identify bacterial strains with enhanced ecological performance in synbiotic applications. Appl. Environ. Microbiol. 81:24552465
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Progress 03/01/14 to 02/28/15
Outputs
Target Audience: The research we are conducting as part of this project should be of interest to researchers and clinicians who study obesity, gut health, and the role of the gut microbiota on obesity and other health conditions. In addition, this research should be of interest to public health officials and scientists who work on obesity-related diseases, especially gut barrier function disorders. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Three graduate students (2.0 FTE) have been working on this project and have been trained in clinical microbiology and bioinformatics. How have the results been disseminated to communities of interest? One publication and severla conferences What do you plan to do during the next reporting period to accomplish the goals? Complete the analyses and publish one or more papers.
Impacts
What was accomplished under these goals?
Emerging evidence indicates that the metabolic inflammation linked to obesity is driven by bacterial molecules that translocate through the intestinal epithelial barrier. Bifidobacteria and prebiotics may improve intestinal barrier function and metabolic pathologies. In this study, our goal was to test the ecological and therapeutic functionality of a synbiotic combination of a Bifidobacterium adolescentis strain (BD1) and the prebiotic galactooligosaccharide (GOS) in a human clinical trial. This synbiotic combination was selected based on the novel concept, In Vivo Selection (IVS). Specifically, the strain was isolated from an individual after being enriched 8-fold in fecal samples through a dietary supplementation of GOS. Using a rat model, we confirmed that BD-1 levels can be increased 90-fold in the colon when the strain is given in combination with GOS. This finding provided a proof of concept for the potential of IVS to identify highly synergistic strain/prebiotic combinations (Krumbeck et al., 2015. Appl. Environ. Microbiol.81:2455-2645). We are currently conducting a randomized, placebo-controlled, parallel-arm clinical trial to test the hypothesis that this rationally selected synbiotic will improve intestinal barrier function in obese adults and thereby prevent endotoxemia and metabolic inflammation. We further hypothesize that this synbiotic will perform better both ecologically and therapeutically when compared with the probiotic alone or with a conventional synbiotic combination. Of our target enrollment of 180 subjects, we have currently enrolled 142 subjects.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
J.A. Krumbeck, M.X. Maldonado-Gomez, I. Mart�nez, S.A. Frese, T.E. Burkey, K. Rasineni, A.E. Ramer-Tait, E.N. Harris, R.W. Hutkins, J. Walter. 2015. In vivo selection to identify bacterial strains with enhanced ecological performance in synbiotic applications. Appl. Environ. Microbiol. 81:24552465
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Progress 03/01/13 to 02/28/14
Outputs
Target Audience: The research we are conducting as part of this project should be of interest to researchers and clinicians that study obesity, gut health, and the role of the gut microbiota on obesity and other health conditions. In addition, this research should be of interest to public health officials and scientists who work on obesity-related diseases, especially gut barrier function disorders. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Three graduate students (2.0 FTE) have been working on this project and have been trained in clinical microbiology and bioinformatics. How have the results been disseminated to communities of interest? We have presented our results at several regional, national, and international conferences via both oral and poster presentations. What do you plan to do during the next reporting period to accomplish the goals? The human trial will be completed and the analyses will commence and be completed by the end of 2015.
Impacts
What was accomplished under these goals?
1. We have recruited and completed the study for more than 100 subjects. Samples have also been collected from these subjects, and analayses have begun. 2. The functionality of IVS-1 and GOS as a synergistic synbiotic has been evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that addition of GOS increased B. adolescentis IVS-1 abundance in the distal gastrointestinal tract by nearly two logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to out-compete the resident Bifidobacterium population when provided GOS. This study demonstrated that IVS can be used to successfully formulate a highly synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2014
Citation:
Kerry Clifford, Bryana Piazza, Ali Keshavarzian, Christy Tangney, Anne Coltman, Chris Hartney, Krista Shawron, Shohreh Raeisi, Christopher Forsyth, Robert Hutkins, Janina Krumbeck, and Heather Rasmussen. The FASEB Journal vol. 28 no. 1 Supplement LB340. Lipopolysaccharide Binding Protein is Associated with Diet Composition and Metabolic Markers in Obese Adults (LB340)
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