Abstract
Objective Estrogen is a critical hormone that is mainly produced by the ovary in females. Estrogen deficiency leads to various syndromes and diseases, partly due to gut microbiota alterations. Previous studies have shown that estrogen deficiency affects the gut microbiota at 6–8 weeks after ovariectomy, but the immediate effect of estrogen deficiency on the gut microbiota remains poorly understood. Methods To investigate the short time and dynamic effects of decreased estrogen levels on the gut microbiota and their potential impact on estrogen deficiency-related diseases, we performed metagenomic sequencing of 260 fecal samples from 50 ovariectomy (OVX) and 15 control C57BL/6 female mice at four time points after surgery. Results We found that seven gut microbiota species, including E. coli, Parabacteroides unclassified, Lachnospiraceae bacterium 8_1_57FAA, Bacteroides uniformis, Veillonella unclassified, Bacteroides xylanisolvens, and Firmicutes bacterium M10_2, were abundant in OVX mice. The abundance of these species increased with time after OVX surgery. The relative abundance of the opportunistic pathogen E. coli and the Crohn's disease-related Veillonella spp. was significantly correlated with mouse weight gain in the OVX group. Butyrate production and the Entner–Doudoroff pathway were significantly enriched in the control mouse group, while the degradation of glutamic acid and aspartic acid was enriched in the OVX mouse group. As the time after OVX surgery increased, the bacterial species and metabolic pathways significantly changed and tended to suggest an inflammatory environment, indicating a subhealthy state of the gut microbiota in the OVX mouse group. Conclusions Taken together, our results show that the dynamic gut microbiota profile alteration caused by estrogen deficiency is related to obesity and inflammation, which may lead to immune and metabolic disorders. This study provides new clues for the treatment of estrogen deficiency-related diseases.
Highlights
Estrogen is the collective name for chemically similar hormones, including estrone, estradiol, estriol, and estetrol, that are mainly secreted by the ovary. e estrogen cycle in females is an essential component of the endocrine system regulating many characteristics of the body in females, such as obesity [1], the production of multiple immune cytokines [2], vascular wall cells [3, 4], and bone metabolism [5, 6].International Journal of EndocrinologyEstrogens play a significant regulatory role in the innate and adaptive immune systems [7, 8]
Our results indicated that the relative abundance of the gut microbiota species, including E. coli, Parabacteroides unclassified, Lachnospiraceae bacterium 8_1_57FAA, Bacteroides uniformis, Veillonella unclassified, Bacteroides xylanisolvens, Peptostreptococcaceae noname unclassified, Parabacteroides distasonis, Dysgonomonas unclassified, Firmicutes bacterium M10_2, and Paraprevotella unclassified, increased over time after OVX surgery (Figure 2), suggesting that the abundance of these gut microbiota gradually increased with the reduction in the estrogen level in mice. e relative abundance of the gut microbiota species, including Dorea unclassified, Acinetobacter unclassified, and Eubacterium cellulosolvens, were not significantly altered at the T1T4 time points
We characterized the alterations of the gut microbiota profile and metabolic pathways after the estrogen level was reduced and confirmed that estrogens contribute to C57BL/ 6 female mouse weight regulation
Summary
Estrogen deficiency leads to various syndromes and diseases, partly due to gut microbiota alterations. To investigate the short time and dynamic effects of decreased estrogen levels on the gut microbiota and their potential impact on estrogen deficiency-related diseases, we performed metagenomic sequencing of 260 fecal samples from 50 ovariectomy (OVX) and 15 control C57BL/6 female mice at four time points after surgery. As the time after OVX surgery increased, the bacterial species and metabolic pathways significantly changed and tended to suggest an inflammatory environment, indicating a subhealthy state of the gut microbiota in the OVX mouse group. Our results show that the dynamic gut microbiota profile alteration caused by estrogen deficiency is related to obesity and inflammation, which may lead to immune and metabolic disorders. Our results show that the dynamic gut microbiota profile alteration caused by estrogen deficiency is related to obesity and inflammation, which may lead to immune and metabolic disorders. is study provides new clues for the treatment of estrogen deficiency-related diseases
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