妊娠中のHIV薬への曝露は,成人ラットの子孫における腸内粘膜に関連する微生物の多様性を変化させる
Yaswanthi Yanamadala1, Chandra Mohan Reddy Muthumula1, Kuppan Gokulan1
1Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, United States.
Experimental biology and medicine (Maywood, N.J.)
|August 29, 2025
まとめ
抗レトロウイルス治療 (ABC/ DTG/ 3TC) の周産期曝露は,老鼠の腸内細菌を変化させる. この薬の組み合わせは腸内粘膜に関連する微生物に影響し,効果は性別と用量によって異なります.
科学分野:
- 微生物学
- 薬理学について
- 発達毒理学
背景:
- アバカビール硫酸,ドゥルテグラビール,ラミブジン (ABC/DTG/3TC) のような抗レトロウイルス薬の組み合わせはHIV治療に不可欠です.
- 子宮内でのARV被曝が子孫の発達に及ぼす長期的な影響について懸念があります.
- 腸内微生物群は 健康に不可欠であり 腸内微生物群の破壊は 免疫機能の調節不良や 炎症と関連しています
研究 の 目的:
- 年老いたネズミの腸内粘膜に関連する微生物群にABC/DTG/3TCの周産期曝露の影響を調査する.
- これらの効果が性別によって異なっており,投与量に依存しているかどうかを判断する.
主な方法:
- ABC/DTG/3TCに生理間接触した老鼠の腸内粘膜関連微生物群の分析
- 微生物の多様性,種多様性,Firmicutes/Bacteroidetes比,そして好機的な細菌種の評価
主要な成果:
- 高用量曝露は雌の子孫の微生物多様性と種多様性を増加させた.
- 女性では,Firmicutes/ Bacteroidetesの比率の量に依存した変化が観察されました.
- 高用量曝露は男性におけるオポルトニスティックな細菌種の増加をもたらした.
- 産後TC-ARTの暴露は,腸内粘膜に関連した性および用量依存の微生物群の変化を引き起こした.
結論:
- TC-ARTの産後暴露は,高齢のラットの腸内粘膜に関連する微生物群を有意に変化させる.
- これらの変化は,薬剤の組み合わせの量と子孫の性別に依存しています.
- これらのARV薬への早期曝露は,腸内粘膜に関連する免疫反応と腸内浸透性に影響を及ぼします.
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