Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-14 DOI:10.1080/19490976.2025.2464942
Salma Singh, Yaa Abu, Danielle Antoine, Daniel Gomez, Junyi Tao, Bridget Truitt, Sabita Roy
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Abstract

The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including Lactobacillus compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.

益生菌补充减轻性别依赖的伤害改变和肠道失调引起的产前阿片类药物暴露。
由于肠道微生物组在健康和疾病中的重要作用,它已成为调节阿片类药物暴露不良反应的有希望的目标。阿片类药物使用障碍(OUD)已变得越来越普遍,特别是在育龄妇女中,导致后代在子宫内接触阿片类药物的发生率增加。最近的研究表明,产前阿片类药物暴露(POE)与母体肠道微生物组的显着变化有关,并对后代的微生物组和其他不良后果产生后续影响。然而,肠道微生物组在调节基于性别的疼痛敏感性差异中的作用尚未被研究。在本研究中,我们使用雄性和雌性C57BL/6后代来确定POE导致的伤害感受和肠道微生物组成的性别差异。我们的数据显示,在产前接触阿片类药物的后代中,存在显著的性别差异。与暴露于阿片类药物的雄性相比,暴露于阿片类药物的雌性肠道微生物组显示出包括乳酸杆菌在内的共生细菌的富集。此外,POE女性表现出伤害性敏感性降低,而男性表现出伤害性敏感性增加。前额叶皮层的RNA测序显示了几个典型通路的性别差异,包括阿片暴露的雌性阿片信号通路的增加,这在雄性中没有观察到。通过母体补充益生菌来改变微生物组,可以在生命早期减弱基于性别的差异。总之,我们的研究为POE引起的基于性别的差异提供了进一步的见解,并强调了肠道微生物组作为减轻其负面影响的可修改目标的关键作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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