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이준영Juneyoung Lee

The University of Texas Health Science Center at Houston

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Gut Microbes, Dec 2023, 15 (2) | https://doi.org/10.1080/19490976.2023.2271629 Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome

Juneyoung Lee ¹, Pedram Peesh ¹, Victoria Quaicoe ¹, Chunfeng Tan ¹, Anik Banerjee ¹, Patrick Mooz ¹, Bhanu P Ganesh ¹, Joseph Petrosino ², Robert M Bryan Jr ³, Louise D McCullough^1,4, Venugopal Reddy Venna ¹

¹Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

²Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.

³Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA.

⁴Department of Neurology, Memorial Hermann Hospital-Texas Medical Center, Houston, TX, USA.

Correspondence : Venugopal Reddy Venna

Abstract

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young males, but not in young females after experimental stroke. In contrast, mucin-related genes were enhanced in young females and contributed to mucus formation that maintains the distance between the host and gut bacteria. Bacterial community profiling was done using universal amplification of 16S rRNA gene sequences. The sex-specific colonic epithelial defense responses after stroke in young females were reversed with ovariectomy and led to a shift from a predominately mucin response to the enhanced AMP expression seen in males after stroke. Estradiol (E ₂) replacement prior to stroke in aged females increased mucin gene expression in the colonic ECs. Interestingly, we found that E ₂ treatment reduced stroke-associated neuronal hyperactivity in the insular cortex, a brain region that interacts with visceral organs such as the gut, in parallel to an increase in the composition of Lactobacillus and Bifidobacterium in the gut microbiota. This is the first study demonstrating sex differences in host defense mechanisms in the gut after brain injury.

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형식Research article
게재일2023년 12월 (BRIC 등록일 2023-11-08)
연구진국외 연구진
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