Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment

• Published in: Microorganisms (Basel) Vol. 11; no. 2; p. 533
• Main Authors: Murali, Aishwarya, Zickgraf, Franziska Maria, Ternes, Philipp, Giri, Varun, Cameron, Hunter James, Sperber, Saskia, Haake, Volker, Driemert, Peter, Kamp, Hennicke, Weyer, Dorothee Funk, Sturla, Shana J, Rietjens, Ivonne M G M, van Ravenzwaay, Bennard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Acetic acid; Animal welfare; Antibiotics; Bacteria; Bile acids; Bioavailability; Carbapenems; Complications and side effects; Composition; Data recovery; Development and progression; Doripenem; Drug dosages; Dysbiosis; Feces; gut microbiome; gut microbiota and metabolome recovery; Health aspects; Hippuric acid; Indoleacetic acid; Indoles; Intestinal microflora; Laboratory animals; Meropenem; Metabolism; Metabolites; metabolomics; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Oral administration; Physiological aspects; Plasma; repeated dose oral study; Risk factors; Testing; Young adults; Germany; carbapenems; gut microbiome; gut microbiota and metabolome recovery; metabolomics; repeated dose oral study
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms11020533

An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.