代謝性疾患は腸内細菌叢と卵巣ホルモンの喪失が原因である可能性を示唆するマウス研究(Mice study suggests metabolic diseases may be driven by gut microbiome, loss of ovarian hormones)

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2024-02-22 イリノイ大学アーバナ・シャンペーン校

新しいマウスの研究によると、女性の性ホルモンの減少と腸内細菌叢の相互作用が、体重増加や肝臓の脂肪、炎症関連遺伝子の発現など、代謝疾患を悪化させる可能性があることがわかった。この研究では、オスの性ホルモンの減少に対する腸内細菌叢の応答が代謝機能の悪化を引き起こす初めての証拠だとされており、女性の更年期後に肥満や糖尿病などの代謝疾患のリスクが高まる理由の一端を明らかにするかもしれない。

<関連情報>

腸内マイクロバイオームは女性ホルモンの状態の変化に反応し、代謝機能障害を悪化させる Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction

Tzu-Wen L. Cross,Abigayle M. R. Simpson,Ching-Yen Lin,Natasha M. Hottmann,Aadra P. Bhatt,Samuel J. Pellock,…
Gut Microbes  Published:28 Dec 2023
DOI:https://doi.org/10.1080/19490976.2023.2295429

Figure 1. Animal characteristics of conventionally raised C57BL/6J mice that underwent either ovariectomy (OVX) or sham (SHM) surgery and fed either a low-fat (LFD) or a high-fat diet (HFD). Final body weight (a) and energy intake (b) at the end of the 12-week study period as well as body weight (c) and energy intake (d) throughout the study time frame are plotted. Total body fat assessed using EchoMRI (e), serum lipopolysaccharide binding protein (LPSBP) concentration (f), liver steatosis (g), and adipocyte cell size (H) were assessed at the end of the study. *denotes main diet effect; +denotes main surgery effect; interactions are denoted either by superscript letters in box plots or by # sign in line graphs, p < .05.

ABSTRACT

Women are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and metabolic dysfunction, but its interaction with female sex hormone status and the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory and metabolic phenotypes as well as the gut microbiome associated with ovariectomy and high-fat diet feeding, compared to gonadal intact and low-fat diet controls. We then performed fecal microbiota transplantation (FMT) using gnotobiotic mice to identify the impact of ovariectomy-associated gut microbiome on inflammatory and metabolic outcomes. We demonstrated that ovariectomy led to greater gastrointestinal permeability and inflammation of the gut and metabolic organs, and that a high-fat diet exacerbated these phenotypes. Ovariectomy also led to alteration of the gut microbiome, including greater fecal β-glucuronidase activity. However, differential changes in the gut microbiome only occurred when fed a low-fat diet, not the high-fat diet. Gnotobiotic mice that received the gut microbiome from ovariectomized mice fed the low-fat diet had greater weight gain and hepatic gene expression related to metabolic dysfunction and inflammation than those that received intact sham control-associated microbiome. These results indicate that the gut microbiome responds to alterations in female sex hormone status and contributes to metabolic dysfunction. Identifying and developing gut microbiome-targeted modulators to regulate sex hormones may be useful therapeutically in remediating menopause-related diseases.

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