Impact of lincosamides antibiotics on the composition of the rat gut microbiota and the metabolite profile of plasma and feces

Behr, Christina; Ramirez-Hincapie, Sabina; Cameron, Hunter James; Strauss, Volker; Walk, T.; Herold, Michael; Beekmann, Karsten; Rietjens, I.M.C.M.; Ravenzwaay, Bennard van

doi:10.1016/j.toxlet.2018.08.002

Cited by 25 publications

(43 citation statements)

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“…However, the colon, harboring 70 % of the total bacteria present in the gut, is the main site for bacterial fermentation [ 37 ]. The bacterial communities in colon and feces have been reported to be highly comparable [ [38] , [39] , [40] ]. Furthermore, proofs of principle that show that anaerobic in vitro incubations using fecal communities can be used to predict intestinal microbial metabolic activities have been reported [ 41 ], supporting the use of anaerobic fecal samples as a representative population of intestinal microbes.…”

Section: Discussionmentioning

confidence: 99%

An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone

et al. 2020

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Section: Discussionmentioning

confidence: 99%

An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone

et al. 2020

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“…In the female animals, roxithromycin showed a slight effect as observed in the feces samples, whereas it showed a similar pattern and clustering with the lincosamides antibiotics. As in our last study, we observed significant changes of the primary bile acids TCA and CA in both plasma and feces (Behr et al, 2018). In general, it was shown that in rat plasma the majority of conjugated bile acids are taurine derivates .…”

Section: Discussionsupporting

confidence: 78%

“…In a recent study, the vehicle control 0.5% CMC showed no significant changes in the microbial community of the rat feces (Behr et al, 2018). Moreover, in this study, the bile acid profiling showed also no significant changes in the feces of both sexes and in plasma of females.…”

Section: Discussionsupporting

confidence: 42%

“…In a previous study, we performed metabolite profiling in plasma and feces of rats after lincosamides treatment in order to establish specific metabolite patterns in the MetaMap ® Tox database and to identify key metabolites indicating gut microbial changes (Behr et al, 2018). The results showed that after treatment, primary bile acids were highly altered in both male and female animals in plasma and feces.…”

Section: Figurementioning

confidence: 99%

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Influence of the gut microbiome on plasma metabolite patterns

Behr¹

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General introduction Chapter 2 25 Gut microbiome-related metabolic changes in plasma of antibiotic-treated rats Chapter 3 55 Microbiome-related metabolite changes in gut tissue, cecum content and feces of rats treated with antibiotics Chapter 4 87 Impact of lincosamides antibiotics on the composition of the rat gut microbiota and the metabolite profile of plasma and feces Chapter 5 Analysis of metabolome changes in the bile acid pool in feces and plasma of antibiotic-treated rats Chapter 6 General discussion Chapter 7 Summary Appendix Acknowledgements, Curriculum Vitae, List of publications, Overview of completed training activities Although the fundamental role of the microbiome in the well-being of the host is clear, science is now dealing with a bigger challenge, i.e. understanding the mechanisms by which these processes of the tight microbial-host interaction are driven. Integrative approaches that not only assess the composition of the gut microbiome but also its functionality must be implemented to unravel the complex dynamics of these interactions [11]. There are high intra-and interspecies variabilities regarding the composition of the microbiome, however, there are also indications that the functionality in terms of gene activity and metabolic output of the microbes have a lower variability [20-22] which supports assessing functional microbial changes with metabolomics approaches. capacity of metabolites, or the first pass metabolism of xenobiotics can influence the host's metabolism or the toxicity of a compound, which may have implications for the host's health. However, since mechanistic studies are mostly performed in rodents, the results are difficult to extrapolate to humans and other species due to the interspecies differences in the composition of the microbiome. Furthermore, the microbiome is influenced by several factors such as a change in diet, the host condition, radiation, xenobiotics and genetics, which results in a high variability regarding the composition of the microbial community within species, but also between different species [14-16,61-63]. Hence, an essential first step is to identify host species-specific effects, e.g. to measure the endogenous metabolite profile, to identify key metabolites and to correlate them to bacterial species. New technologies such as the omics technologies enable a deep research of the complex interaction between microbiome and host, potentially having the power to elucidate its outstanding role in the developing organism. To understand its role in toxicology and pharmacology, it is essential to determine the microbiota's function, composition, community organization, and resulting host-microbiota interactions. Omics technologies, especially metabolomics, can be suitable tools to identify microbiome-derived orassociated metabolites and to reflect changes in the composition of the microbiota that could potentially lead to disease [18]. Analyzing the production of microbiota-derived metabolites is the first stage of a series of investigations that have th...

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“…[ 24 ] Furthermore, it has been shown that the bacterial communities in colon and feces are highly comparable. [ 25–27 ] In addition, proofs of principle have shown that anaerobic in vitro incubations using fecal communities can be used to predict intestinal microbial metabolic activities, [ 24 ] supporting the use of anaerobic fecal samples as a representative population of intestinal microbes.…”

Section: Discussionmentioning

confidence: 99%

Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

Jin

Spenkelink

Beekmann

et al. 2021

Molecular Nutrition Food Res

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Scope Deoxynivalenol (DON) and its acetylated derivatives 3‐acetyl‐DON (3‐Ac‐DON) and 15‐acetyl‐DON (15‐Ac‐DON) are important mycotoxins of concern in the modern food chain. Methods and Results The present study reveals that the rate of de‐acetylation in in vitro anaerobic fecal incubations decreased in the order rat > mouse > human > pig for 3‐Ac‐DON, and mouse > human > rat > pig for 15‐Ac‐DON. The ratio between the de‐acetylation rate of 3‐Ac‐DON and 15‐Ac‐DON varies with the species. Scaling of the kinetic parameters to the in vivo situation results in catalytic efficiencies decreasing in the order human > rat > pig > mouse for 3‐Ac‐DON and human > pig > rat > mouse for 15‐Ac‐DON. The results obtained indicate that in mice, 3‐Ac‐DON can be fully deconjugated while 15‐Ac‐DON cannot. In rats, pigs, and humans, both 3‐Ac‐DON and 15‐Ac‐DON can be totally transformed by gut fecal microbiota during the estimated intestinal residence time. A correlation analysis between the deacetylation rate and the relative abundance of the microbiome suggests Lachnospiraceae may be involved in the deacetylation process. Conclusion It is concluded that interspecies differences in deacetylation of acetylated DONs exist but that in risk assessment assumption of complete intestinal deconjugation provides an adequate approach.

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Impact of lincosamides antibiotics on the composition of the rat gut microbiota and the metabolite profile of plasma and feces

Cited by 25 publications

References 41 publications

An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone

An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone

Influence of the gut microbiome on plasma metabolite patterns

Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

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