BRIEF RESEARCH REPORT article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1556344
Heat-killed Lactobacillus acidophilus suppresses SARS-CoV-2 infection in the human intestinal epithelial cell line Caco-2
Provisionally accepted
Kazuhide Takada1,2*
Quang Trinh1,2
Yoshinori Takeda1,3
Noriko M Tsuji1,2,4
Satoshi Hayakawa1,2
Shihoko Komine-Aizawa1,2- 1Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
- 2Division of Immune Homeostasis, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
- 3Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan
- 4Department of Food Science, Jumonji University, Saitama, Kanagawa, Japan
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The gastrointestinal (GI) tract is suspected to be a possible source for the systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as a reservoir of long coronavirus disease (COVID). Thus, the mucosal epithelial tissue of the colon is a potential target for probiotics to help control SARS-CoV-2 infection. Recently, the effect of live probiotics on COVID-19 has been evaluated. However, live probiotics have certain risks, including the transmission of antibiotic-resistant genes, disturbance of gut colonization in infants, and systemic infections induced by translocation. Therefore, there is growing interest in nonviable microorganisms, particularly heat-killed probiotic bacteria, to mitigate these risks.This study evaluated the antiviral properties of heat-killed Lactobacillus acidophilus (HK-LA) in the Caco-2 cell line. Caco-2 cells were infected by SARS-CoV-2 with or without 24-hour pretreatment of HK-LA and the presence of HK-LA during infection.RT-qPCR analysis showed that HK-LA treatment significantly reduced SARS-CoV-2 genome copies by approximately 30%. Similarly, flow cytometry revealed a roughly 30% decrease in SARS-CoV-2 spike-positive Caco-2 cells following HK-LA treatment.Additionally, ELISA demonstrated a significant increase in IFN-λ2 secretion induced by HK-LA.HK-LA reduces viral infection in Caco-2 cells with an increase in IFN-λ2 secretion.Therefore, heat-killed lactobacilli could potentially reduce SARS-CoV-2 infection in the GI tract, suggesting a possible clinical application.
Keywords: COVID-19, Long Covid, Probiotics, gut, Lactobacillus, SARS-CoV-2
Received: 14 Jan 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Takada, Trinh, Takeda, Tsuji, Hayakawa and Komine-Aizawa. 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: Kazuhide Takada, Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.