Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 319; no. 2; pp. G227 - G237
• Main Authors: Qian, Xi, Yanagi, Karin, Kane, Anne V., Alden, Nicholas, Lei, Ming, Snydman, David R., Vickers, Richard J., Lee, Kyongbum, Thorpe, Cheleste M.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2020
• Series: Microbiome and Host Interactions
• Subjects: Acids; Anti-Bacterial Agents - pharmacology; Antibiotics; Benzimidazoles - pharmacology; Bile; Bile acids; Bile Acids and Salts - chemistry; Bile Acids and Salts - metabolism; Clostridiales - drug effects; Correlation analysis; Digestive system; Dysbacteriosis; Feces - chemistry; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Humans; Infections; Intestinal microflora; Intestine; Microbiota; Preservation; Pyridines - pharmacology; Risk factors; Vancomycin; longitudinal outcome; Clostridioides difficile infection; antibiotic therapy; bile acid
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00046.2020

This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent’s favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment. Antibiotic treatment is a standard therapy for Clostridioides difficile infection, but dysbiosis of the gut microbiota due to antibiotic exposure is also a major risk factor for the disease. Following an initial episode of C. difficile infection, a relentless cycle of recurrence can occur, where persistent treatment-related dysbiosis predisposes the patient to subsequent relapse. This study uses a longitudinal study design to compare the effects of a narrow-spectrum (ridinilazole) or broad-spectrum antibiotic (vancomycin) on intestinal bile acid profiles and their associations with gut bacteria over the course of C. difficile infection treatment. At the end of treatment ( day 10), subjects receiving vancomycin showed a nearly 100-fold increase in the ratio of conjugated to secondary bile acids in their stool compared with baseline, whereas subjects receiving ridinilazole maintained this ratio near baseline levels. Correlation analysis detected significant positive associations between secondary bile acids and several Bacteroidales and Clostridiales families. These families were depleted in the vancomycin group but preserved at near-baseline abundance in the ridinilazole group. Enterobacteriaceae, which expanded to a greater extent in the vancomycin group, correlated negatively and positively with secondary and conjugated primary bile acids, respectively. Bile acid ratios at the end of treatment were significantly different between those who recurred and those who did not. These results indicate that a narrow-spectrum antibiotic maintains an intestinal bile acid profile associated with a lowered risk of recurrence. NEW & NOTEWORTHY This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent’s favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment.