Sex differences and hormonal effects on gut microbiota composition in mice.
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ABSTRACT:
SUBMITTER: Org E
PROVIDER: S-EPMC4988450 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Sex differences and hormonal effects on gut microbiota composition in mice.
Org Elin E Mehrabian Margarete M Parks Brian W BW Shipkova Petia P Liu Xiaoqin X Drake Thomas A TA Lusis Aldons J AJ
Gut microbes 20160629 4
We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also exami ...[more]
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Project description:BackgroundEvidence was previously provided for sex-related differences in the human gut microbiota composition, and sex-specific discrepancy in hormonal profiles was proposed as a main determinant of these differences. On the basis of these findings, the assumption was made on the role of microbiota in the sexual dimorphism of human diseases. To date, sex differences in fecal microbiota were demonstrated primarily at lower taxonomic levels, whereas phylum-level differences between sexes were reported in few studies only. In the present population-based cross-sectional research, sex differences in the phylum-level human gut microbiota composition were identified in a large (total n = 2301) sample of relatively healthy individuals from Ukraine.ResultsRelative abundances of Firmicutes and Actinobacteria, as determined by qRT-PCR, were found to be significantly increased, while that of Bacteroidetes was significantly decreased in females compared to males. The Firmicutes to Bacteroidetes (F/B) ratio was significantly increased in females compared to males. Females had 31 % higher odds of having F/B ratio more than 1 than males. This trend was evident in all age groups. The difference between sexes was even more pronounced in the elder individuals (50+): in this age group, female participants had 56 % higher odds of having F/B ratio > 1 than the male ones.ConclusionsIn conclusion, sex-specific differences in the phylum-level intestinal microbiota composition were observed in the Ukraine population. The F/B ratio was significantly increased in females compared to males. Further investigation is needed to draw strong conclusions regarding the mechanistic basis for sex-specific differences in the gut microbiota composition and regarding the role of these differences in the initiation and progression of human chronic diseases.
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Project description:Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and "off-label" indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an "obesogenic" profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37-65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.
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