# Heat-killed Lactobacillus acidophilus suppresses SARS-CoV-2 infection in the human intestinal epithelial cell line Caco-2

**Authors:** Kazuhide Takada, Quang Duy Trinh, Yoshinori Takeda, Noriko M. Tsuji, Satoshi Hayakawa, Shihoko Komine-Aizawa

PMC · DOI: 10.3389/fcimb.2025.1556344 · 2025-07-31

## TL;DR

Heat-killed Lactobacillus acidophilus reduces SARS-CoV-2 infection in intestinal cells and boosts antiviral protein production.

## Contribution

Demonstrates that heat-killed Lactobacillus acidophilus suppresses SARS-CoV-2 in Caco-2 cells, offering a safer probiotic alternative.

## Key findings

- HK-LA reduced SARS-CoV-2 genome copies by about 30% in Caco-2 cells.
- HK-LA decreased spike-positive cells by approximately 30% as shown by flow cytometry.
- HK-LA treatment significantly increased IFN-λ2 secretion in infected cells.

## Abstract

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.

## Linked entities

- **Proteins:** IFNL2 (interferon lambda 2)
- **Species:** Lactobacillus acidophilus (taxon 1579), Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** IFNL2 (interferon lambda 2) [NCBI Gene 282616] {aka IFNL2a, IFNL3a, IL-28A, IL28A}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}
- **Diseases:** COVID (MESH:D018352), COVID-19 (MESH:D000086382), long coronavirus disease (MESH:D000094024), infection (MESH:D007239)
- **Species:** Lactobacillus acidophilus (species) [taxon 1579], Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]
- **Cell lines:** Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12350398/full.md

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Source: https://tomesphere.com/paper/PMC12350398