ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
This article is part of the Research TopicThe Role of Gut Microbiota in Animal Gastrointestinal Diseases Volume IIView all articles
Ellagic Acid Mitigates Rotavirus-Induced Intestinal Injury via bidirectional "immune-microbiota" regulatory effect
Provisionally accepted
- 1Changzhi Medical College, Changzhi, China
- 2Shanxi Agricultural University, Taiyuan, China
- 3Xinjiang Medical University, Urumqi, China
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In this study, rotavirus (RV) was used to infect BALB/c suckling mouse models to explore whether ellagic acid could alleviate intestinal damage following rotavirus infection through bidirectional regulation of "immunity and microbiota". The viral load of RV, the expression levels of IL-1β, IL-6, and TNF-α mRNA were detected by qPCR. The pathological changes in the jejunal tissue were observed by hematoxylin and eosin (H&E) staining. The expression of JAM1, ZO-1, and Claudin-4 proteins in jejunal tissue were detected by immunohistochemistry (IHC). The expressions of TLR4, MYD88, IκBα, and P-P65 proteins in jejunal tissues were detected by WB. 16S rDNA gene sequencing was employed to detect the structural changes of the microbiota in feces, and qPCR was used to detect the colonization of Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus gasseri in jejunal tissues. The qPCR results revealed that ellagic acid could significantly (P < 0.001) reduce the viral load as well as the mRNA expression levels of IL-1β, IL-6, and TNF-α in RV-infected BALB/c suckling mice. The results of H&E staining demonstrated that ellagic acid could alleviate villus rupture and vacuolation lesions induced by RV and significantly (P < 0.05) alleviate intestinal villus shortening and crypt deepening caused by RV. The IHC results showed that ellagic acid could significantly increase the expression of tight junction proteins JAM1, ZO-1, and Claudin-4 in RV-infected BALB/c neonatal mice. The WB results showed that ellagic acid significantly (P < 0.001) inhibited the expression of the TLR4/NF-κB signaling pathway. The results of 16S rDNA gene sequencing showed that ellagic acid could lead to a significant (P < 0.05) increase in the abundance of intestinal Lactobacillus bacteria (Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus gasseri, etc.) in RV-infected BALB/c suckling mice. Ellagic acid can also significantly promote the colonization of Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus gasseri in the jejunum. In conclusion, Ellagic acid can alleviate intestinal damage following rotavirus infection through bidirectional regulation of "immunity and microbiota", providing a theoretical foundation and innovative concepts for the research and development of EA as an anti-RV drug.
Keywords: Ellagic Acid, Rotavirus, BALB/c suckling mouse, TLR4, Lactobacillus johnsonii
Received: 16 Aug 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Zheng, Cao, Yousaf, Haseeb, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hejie Wang
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