[P008] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P04-600] Microbiome-targeted interventions can alleviate Clostridioides difficile infection exacerbated by gastric acid suppression

○Yu-Ting Lin¹, Yuan-Pin Hung^2,1, Chih-Hsuan Tsai¹ (1. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University (Taiwan), 2. Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Taiwan (Taiwan))

Keywords:

Clostridioides difficile infection,Gut microbiota,Microbiome-targeted intervention,Bifidobacterium longum

Gut microbiota is a key determinant of intestinal homeostasis, driving the production of metabolites that regulate host physiology and confer colonization resistance against opportunistic pathogens. However, this microbiota composition is highly sensitive to environmental conditions, such as luminal pH. Acid-suppressive therapies that increase luminal pH have been reported to create an environment conducive to pathogen colonization and disease onset. In this study, we aimed to investigate whether microbiome-targeted restoration strategies, independent of antibiotics, can alleviate the aggravated disease outcomes induced by Clostridioides difficile infection (CDI) during acid-suppressive therapy. In vitro assays showed that C. difficile spore germination was significantly elevated within the pH range of 5–8. Correspondingly, our CDI murine model revealed that gastric pH elevation after administration of acid-suppressive drugs was associated with increased CDI severity. 16S rRNA gene sequencing of gut microbiota demonstrated that elevated pH reduced microbial diversity and depleted key fermentative taxa, particularly Bifidobacterium longum. Metabolome analysis revealed an increase of harmful branched-chain fatty acids in the acid-suppressive drug treatment groups, indicating disrupted microbial metabolic networks. These changes were also associated with epithelial barrier dysfunction, including reduced tight junction gene (ZO-1 and occludin) expression and increased pro-inflammatory cytokine gene (IL-1β and IL-8) expression. Notably, oral gavage of B. longum in mice could partially alleviate the exacerbated CDI during gastric acid suppression, including reduced toxin production, decreased pro-inflammatory cytokine expression, and improved epithelial barrier integrity. We are now exploring physiological regulation methods to enhance this targeted microbial restoration performance. In summary, after microbiota analysis, a microbiome-targeted intervention can potentially alleviate CDI exacerbated by elevated gut pH, suggesting possible future complementary treatments in addition to antibiotic administration.