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      Effects of coconut oil on glycemia, inflammation, and urogenital microbial parameters in female Ossabaw mini-pigs

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          Abstract

          Forty percent of American women are obese and at risk for type II diabetes, impaired immune function, and altered microbiome diversity, thus impacting overall health. We investigated whether obesity induced by an excess calorie, high fat diet containing hydrogenated fats, fructose, and coconut oil (HFD) altered glucose homeostasis, peripheral immunity, and urogenital microbial dynamics. We hypothesized that HFD would cause hyperglycemia, increase peripheral inflammation, and alter urogenital microbiota to favor bacterial taxonomy associated with inflammation. We utilized female Ossabaw mini-pigs to model a ‘thrifty’ metabolic phenotype associated with increased white adipose tissue mass. Pigs were fed HFD (~4570 kcal/pig/day) or lean (~2000 kcal/pig/day) diet for a total of 9 estrous cycles (~6 months). To determine the effect of cycle stage on cytokines and the microbiome, animals had samples collected during cycles 7 and 9 on certain days of the cycle: D1, 4, 8, 12, 16, 18. Vaginal swabs or cervical flushes assessed urogenital microbiota. Systemic fatty acids, insulin, glucose, and cytokines were analyzed. Pig weights and morphometric measurements were taken weekly. Obese pigs had increased body weight, length, heart and belly girth but similar glucose concentrations. Obese pigs had decreased cytokine levels (IL-1β, TNF-α, IL-4, IL-10), arachidonic acid and plasma insulin, but increased levels of vaccenic acid. Obese pigs had greater urogenital bacterial diversity, including several taxa known for anti-inflammatory properties. Overall, induction of obesity did not induce inflammation but shifted the microbial communities within the urogenital tract to an anti-inflammatory phenotype. We postulate that the coconut oil in the HFD oil may have supported normal glucose homeostasis and modulated the immune response, possibly through regulation of microbial community dynamics and fatty acid metabolism. This animal model holds promise for the study of how different types of obesity and high fat diets may affect metabolism, immune phenotype, and microbial dynamics.

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          Most cited references36

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          Vaginal pH and Microbicidal Lactic Acid When Lactobacilli Dominate the Microbiota

          Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 ± 0.3 (mean ± SD), range 2.8-4.2, and the average total lactate was 1.0% ± 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.
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            Evaluation of 16S rDNA-Based Community Profiling for Human Microbiome Research

            (2012)
            The Human Microbiome Project will establish a reference data set for analysis of the microbiome of healthy adults by surveying multiple body sites from 300 people and generating data from over 12,000 samples. To characterize these samples, the participating sequencing centers evaluated and adopted 16S rDNA community profiling protocols for ABI 3730 and 454 FLX Titanium sequencing. In the course of establishing protocols, we examined the performance and error characteristics of each technology, and the relationship of sequence error to the utility of 16S rDNA regions for classification- and OTU-based analysis of community structure. The data production protocols used for this work are those used by the participating centers to produce 16S rDNA sequence for the Human Microbiome Project. Thus, these results can be informative for interpreting the large body of clinical 16S rDNA data produced for this project.
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              How obesity causes diabetes: not a tall tale.

              The epidemic of obesity-associated diabetes is a major crisis in modern societies, in which food is plentiful and exercise is optional. The biological basis of this problem has been explored from evolutionary and mechanistic perspectives. Evolutionary theories, focusing on the potential survival advantages of "thrifty" genes that are now maladaptive, are of great interest but are inherently speculative and difficult to prove. Mechanistic studies have revealed numerous fat-derived molecules and a link to inflammation that, together, are hypothesized to underlie the obesity-diabetes connection and thereby represent prospective targets for therapeutic intervention.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Investigation
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Supervision
                Role: MethodologyRole: ResourcesRole: SoftwareRole: Supervision
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 July 2017
                2017
                : 12
                : 7
                : e0179542
                Affiliations
                [1 ] Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, United States of America
                [2 ] Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [3 ] Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America
                [4 ] Carl R. Woese Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [5 ] Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America
                INIA, SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-1878-5892
                Article
                PONE-D-17-09435
                10.1371/journal.pone.0179542
                5509134
                28704429
                9b942fac-bc6f-49b6-8c97-a0edd5ced86f
                © 2017 Newell-Fugate et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 March 2017
                : 31 May 2017
                Page count
                Figures: 6, Tables: 3, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: K01 RR031274-01A21
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000199, U.S. Department of Agriculture;
                Award ID: ILLU 538-370
                Award Recipient :
                This work was supported by: 1) NIH K01 RR031274-01A21 (ANF); http://dpcpsi.nih.gov/orip/index; 2) USDA ILLU 538-370 (RAN); https://nifa.usda.gov/grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Swine
                Biology and Life Sciences
                Nutrition
                Diet
                Medicine and Health Sciences
                Nutrition
                Diet
                Biology and Life Sciences
                Biochemistry
                Lipids
                Oils
                Biology and Life Sciences
                Agriculture
                Agronomy
                Plant Products
                Vegetable Oils
                Biology and Life Sciences
                Agriculture
                Crop Science
                Plant Products
                Vegetable Oils
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Inflammation
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Inflammation
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Pig Models
                Custom metadata
                All sequencing data files are available in the NCBI biosample repository. Our Bioproject ID is: PRJNA392333. You can find all individual accession numbers in this Bioproject https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA392333.

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