Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Acharya, Kalpana D.; Noh, Hye Lim; Graham, Madeline; Suk, Sujin; Friedline, Randall H.; Gomez, Cesiah C; Parakoyi, Abigail E.R.; Kim, Jason K.; Tetel, Marc J.

doi:10.3390/metabo11080499

Cited by 17 publications

(26 citation statements)

References 116 publications

(168 reference statements)

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“…Differences in sex hormone levels are primarily responsible for the sexually dimorphic microbiome. Existing studies have proven that the gut microbiota is involved in the physiological roles of sex hormones, and intestinal flora can also be regulated by hormones [ 61 , 62 ]. In addition, the existence of estrogen is an important factor affecting the degree of post-stroke injury [ 63 ]; therefore, changes in this hormone may also be one of the intermediate links in the process of flora exchange.…”

Section: Discussionmentioning

confidence: 99%

“…The male intestinal environment is conducive to the survival of Firmicutes, producing a large amount of TMAO, which promotes the production of proinflammatory factors and the infiltration of inflammatory cells in the brain, eventually aggravating central inflammation. flora can also be regulated by hormones [61,62]. In addition, the existence of estrogen is an important factor affecting the degree of post-stroke injury [63]; therefore, changes in this hormone may also be one of the intermediate links in the process of flora exchange.…”

Section: Discussionmentioning

confidence: 99%

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Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Wang

Zhong

Zhu

et al. 2022

J Neuroinflammation

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Background and purpose Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown. Methods To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis. Results We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function. Conclusion A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Wang

Zhong

Zhu

et al. 2022

J Neuroinflammation

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“…The increase of Streptococcaceae is inversely proportional to E 2 . Moreover, the alteration of the gut microbiome can affect metabolic homeostasis, which is mediated by E 2 [ 54 ]. Although the content of probiotics could be increased by EN in this study, the dominant bacteria were pathogenic bacteria.…”

Section: Discussionmentioning

confidence: 99%

Effects of Electroacupuncture on the Gut Microbiome in Cisplatin-Induced Premature Ovarian Failure Mice

Guo

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Growing evidence showed that the gut microbiota was associated with premature ovarian failure (POF). Many clinical types of research had shown that electroacupuncture was effective in the treatment of POF. However, there was little research on regulating the gut microbiome of POF mice by electroacupuncture. Therefore, this study attempted to verify whether electroacupuncture could regulate the gut microbiome in POF mice. POF mice were established by being injected intraperitoneally with cisplatin (2 mg/kg) for 2 weeks. Guanyuan (CV4) and Sanyinjiao (SP6) were selected in the electroacupuncture-at-the-acupoints group (EA group). Nonacupoints around CV4 and SP6 were selected in the electroacupuncture-at-the-nonacupoints group (EN group). The EA group and EN group were treated for 3 weeks. The ovarian function was evaluated by histopathological and molecular assays. Meanwhile, the gut microbiome of all mice was detected by 16S rDNA sequencing. The results showed that EA could restore the estrous cycle and reduce the number of atresia follicles in POF mice. The levels of serum follicle-stimulating hormone and luteinizing hormone were decreased by EA. As well, the levels of serum estradiol, anti-Mullerian hormone, and β-glucuronidase were increased by EA. The relative expressions of PI3K, AKT, and mTOR were increased to promote the proliferation of ovarian cells in the EA group. According to the results of 16S rDNA sequencing, the abundance and diversity of the gut microbiome could be regulated by EA. The relative abundance of beneficial bacteria was increased by EA. The KEGG pathway analysis showed that the gut microbiome associated with the estrogen signaling pathway, oocyte maturation, and PI3K-AKT signaling pathway was regulated by EA.

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“…Among several factors which can influence the composition of the gut microbiota, sex is a major contributor [ 7 ]. Both human and animal studies, mainly performed in mice, have reported sex-related differences in the gut microbiota [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ], and a role has been proposed for sex steroid hormones in contributing to this sexual dimorphism [ 9 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Additionally, inhibition of key enzymes in steroidogenesis, such as 5-alpha-reductase (5α-R), alters gut microbiota populations in rodents and humans [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Steroids and Microbiota: Effect of Gonadectomy and Sex

et al. 2022

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Sex steroids, derived mainly from gonads, can shape microbiota composition; however, the impact of gonadectomy and sex on steroid production in the gut (i.e., gut steroids), and its interaction with microbiota composition, needs to be clarified. In this study, steroid environment and gut steroidogenesis were analysed by liquid chromatography tandem mass spectrometry and expression analyses. Gut microbiota composition as branched- and short-chain fatty acids were determined by 16S rRNA gene sequence analysis and gas chromatography flame ionisation detection, respectively. Here, we first demonstrated that levels of pregnenolone (PREG), progesterone (PROG), and isoallopregnanolone (ISOALLO) were higher in the female rat colon, whereas the level of testosterone (T) was higher in males. Sexual dimorphism on gut steroidogenesis is also reported after gonadectomy. Sex, and more significantly, gonadectomy, affects microbiota composition. We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between Blautia with T, dihydroprogesterone (DHP), and allopregnanolone (ALLO), whereas negative associations were noted between Roseburia and T, ALLO, PREG, ISOALLO, DHP, and PROG. In conclusion, this study highlights the novel sex-specific association between microbiota and gut steroids with possible relevance for the gut-brain axis.

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Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Cited by 17 publications

References 116 publications

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Effects of Electroacupuncture on the Gut Microbiome in Cisplatin-Induced Premature Ovarian Failure Mice

Gut Steroids and Microbiota: Effect of Gonadectomy and Sex

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