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Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: “Personalized” effect?
Abstract The human gut microbiome (GM) in healthy people is chronically exposed to tetracycline (TET) via environmental exposure and dietary uptake. However, limited information is available on its effect on the GM metabolome and effect on the host, especially at the dietary exposure level. Here, we investigated how TET at both sub-pharmaceutical and dietary exposure levels affects the metabolome and the secretome-induced host immune response by studying several representative gut bacteria. Interestingly, the metabolome showed a highly species-specific pattern with a distinct dose-response relationship. B. fragilis was highly sensitive to TET and vitamin, nucleotide, and amino acid metabolism pathways were the most vulnerable metabolic pathways at dietary exposure level. For key metabolite short chain fatty acids, TET significantly induced the synthesis of butyrate in B. fragilis, rather than C. sporogenes and E. coli. Furthermore, TET induced the release of lipopolysaccharides (LPS) in E. coli and enhanced the immune response; however, there was no obvious effect on B. fragilis. Interestingly, the overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis, possibly due to the neutralization of active LPS from E. coli by the LPS from B. fragilis. Overall, our results showed that the effect of TET from environmental exposure on the host health would be highly dependent on the GM composition, especially for the gut bacterial metabolome and secretome induced immune response.
Graphical abstract Display Omitted
Highlights The gut bacterial metabolome showed a species-specific, dose dependent response towards tetracycline (TET). Vitamin, nucleotide, and amino acid metabolism pathways were highly affected at dietary exposure level. TET significantly induced the synthesis of butyrate in B. fragilis. The overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis.
Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: “Personalized” effect?
Abstract The human gut microbiome (GM) in healthy people is chronically exposed to tetracycline (TET) via environmental exposure and dietary uptake. However, limited information is available on its effect on the GM metabolome and effect on the host, especially at the dietary exposure level. Here, we investigated how TET at both sub-pharmaceutical and dietary exposure levels affects the metabolome and the secretome-induced host immune response by studying several representative gut bacteria. Interestingly, the metabolome showed a highly species-specific pattern with a distinct dose-response relationship. B. fragilis was highly sensitive to TET and vitamin, nucleotide, and amino acid metabolism pathways were the most vulnerable metabolic pathways at dietary exposure level. For key metabolite short chain fatty acids, TET significantly induced the synthesis of butyrate in B. fragilis, rather than C. sporogenes and E. coli. Furthermore, TET induced the release of lipopolysaccharides (LPS) in E. coli and enhanced the immune response; however, there was no obvious effect on B. fragilis. Interestingly, the overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis, possibly due to the neutralization of active LPS from E. coli by the LPS from B. fragilis. Overall, our results showed that the effect of TET from environmental exposure on the host health would be highly dependent on the GM composition, especially for the gut bacterial metabolome and secretome induced immune response.
Graphical abstract Display Omitted
Highlights The gut bacterial metabolome showed a species-specific, dose dependent response towards tetracycline (TET). Vitamin, nucleotide, and amino acid metabolism pathways were highly affected at dietary exposure level. TET significantly induced the synthesis of butyrate in B. fragilis. The overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis.
Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: “Personalized” effect?
Keerthisinghe, Tharushi P. (Autor:in) / Wang, Mengjing (Autor:in) / Zhang, Yingdan (Autor:in) / Dong, Wu (Autor:in) / Fang, Mingliang (Autor:in)
30.06.2019
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
GM , gut microbiome , TET , tetracycline , LPS , lipopolysaccharides , GI , gastrointestinal , TMAO , trimethylamine N-oxide , BCAAs , branched chain amino acids , SCFAs , short chain fatty acids , RCM , reinforced clostridial medium , IC , inhibitory concentration , HPLC , high performance liquid chromatography , DDA , data-dependent acquisition , PBS , phosphate buffered saline , PCA , principal component analysis , PFBBr , 2,3,4,5,6‑penta‑fluorobenzyl bromide , GC–MS , gas chromatography–mass spectrometry , MSD , mass selective detector , LAL , limulus amebocyte lysate , PMA , phorbol 12‑myristate 13‑acetate , TNF , tumor necrosis factor , IL , interleukin , RSD , relative standard deviation , CLA , conjugated linoleic acids , Gut bacteria , Tetracycline , Metabolism , Immune response
DOAJ | 2019
|Elsevier | 2024
|DOAJ | 2024
|Elsevier | 2024
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