AUTHOR=Chathuranga Kiramage , Shin Yeseul , Uddin Md Bashir , Paek Jayoung , Chathuranga W. A. Gayan , Seong Yebin , Bai Lu , Kim Hongik , Shin Jeong Hwan , Chang Young-Hyo , Lee Jong-Soo 

TITLE=The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1242183

DOI=10.3389/fimmu.2023.1242183

ISSN=1664-3224

ABSTRACT=<p><italic>Clostridium butyricum</italic> is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of <italic>C. butyricum</italic> from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses <italic>in vitro</italic> and <italic>in vivo</italic>. The isolated <italic>C. butyricum</italic> S-45-5 showed typical characteristics of <italic>C. butyricum</italic> including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, <italic>C. butyricum</italic> S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells <italic>in vitro</italic>. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. <italic>In vivo</italic>, oral administration of <italic>C. butyricum</italic> S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, <italic>C. butyricum</italic> S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, <italic>C. butyricum</italic> S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that <italic>C. butyricum</italic> S-45-5 plays an antiviral role <italic>in vitro</italic> and <italic>in vivo</italic> by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new <italic>C. butyricum</italic> S-45-5 with antiviral effects as a probiotic.</p>