ADS024, a Bacillus velezensis strain, protects human colonic epithelial cells against C. difficile toxin-mediated apoptosis

Ying Xie; Andrea Chupina Estrada; Becca Nelson; Hanping Feng; Charalabos Pothoulakis; Laurent Chesnel; Hon Wai Koon

doi:10.3389/fmicb.2022.1072534

ADS024, a Bacillus velezensis strain, protects human colonic epithelial cells against C. difficile toxin-mediated apoptosis

Front Microbiol. 2023 Jan 10:13:1072534. doi: 10.3389/fmicb.2022.1072534. eCollection 2022.

Authors

Ying Xie^{1

2}, Andrea Chupina Estrada¹, Becca Nelson¹, Hanping Feng³, Charalabos Pothoulakis¹, Laurent Chesnel⁴, Hon Wai Koon¹

Affiliations

¹ Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, United States.
² Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
³ Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, College Park, College Park, MD, United States.
⁴ Adiso Therapeutics Inc., Concord, MA, United States.

Abstract

Clostridioides difficile infection (CDI) causes intestinal injury. Toxin A and toxin B cause intestinal injury by inducing colonic epithelial cell apoptosis. ADS024 is a Bacillus velezensis strain in development as a single-strain live biotherapeutic product (SS-LBP) to prevent the recurrence of CDI following the completion of standard antibiotic treatment. We evaluated the protective effects of the sterile filtrate and ethyl acetate extract of conditioned media from ADS024 and DSM7 (control strain) against mucosal epithelial injury in toxin-treated human colonic tissues and apoptosis in toxin-treated human colonic epithelial cells. Ethyl acetate extracts were generated from conditioned culture media from DSM7 and ADS024. Toxin A and toxin B exposure caused epithelial injury in fresh human colonic explants. The sterile filtrate of ADS024, but not DSM7, prevented toxin B-mediated epithelial injury in fresh human colonic explants. Both sterile filtrate and ethyl acetate extract of ADS024 prevented toxin-mediated apoptosis in human colonic epithelial cells. The anti-apoptotic effects of ADS024 filtrate and ethyl acetate extract were dependent on the inhibition of caspase 3 cleavage. The sterile filtrate, but not ethyl acetate extract, of ADS024 partially degraded toxin B. ADS024 inhibits toxin B-mediated apoptosis in human colonic epithelial cells and colonic explants.

Keywords: C. difficile; apoptosis; biologic; infection; single-strain live biotherapeutic product; therapy.

Grants and funding

The authors declare that this study received funding from Adiso Therapeutic. Adiso Therapeutic was not involved in the study design, collection, analysis, interpretation of data, but Adiso Therapeutic was involved in the writing of this article, or the decision to submit it for publication. LC was employed by Adiso Therapeutics.