Biotransformation of Celecoxib Using Microbial Cultures

Srisailam, K.; Veeresham, Ciddi

doi:10.1007/s12010-009-8789-3

Cited by 20 publications

(13 citation statements)

References 38 publications

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“…Celecoxib is metabolized by many microbial species (2) and has broad antimicrobial activity against Gram-positive bacteria, as well as Gram-negatives when supplemented with membrane permeabilizing agents (3). Although inter-individual differences remained following treatment, the brief administration of the drug is a weakness of our study.…”

mentioning

confidence: 99%

Celecoxib does not alter intestinal microbiome in a longitudinal diet-controlled study

Bokulich

Battaglia

Alemán

et al. 2016

Clinical Microbiology and Infection

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confidence: 99%

Celecoxib does not alter intestinal microbiome in a longitudinal diet-controlled study

Bokulich

Battaglia

Alemán

et al. 2016

Clinical Microbiology and Infection

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“…This biotransformation method was done according to the reported method [40], with few modifications. Briefly, the second stage suspension cultures (25 mL) of all experimental organisms were added with racemic Carvedilol solution in methanol (0.01 mg/mL culture).…”

Section: Methodsmentioning

confidence: 99%

“…This process was repeated for three times and the combined organic phase was evaporated and dried in vacuum oven [40]. The residues were reconstituted with 1 mL methanol (HPLC grade), filtered through sterile filters (pore size-0.22 µm) and were analyzed by chiral HPLC.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Resolution of (R,S)-Carvedilol to (S)-(−)-Carvedilol by Biocatalysts

Swetha

Chandupatla

Veeresham

2017

Nat. Prod. Bioprospect.

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Among the microorganisms employed in the study, Aspergillus niger (GUFCC5443), Escherichia coli (ATCC9637), Streptomyces halstedii (CKM-2), Pseudomonas putida (NCIB9494), Cunninghamella elegans (NCIM689) and Sphingomonas paucimobilis (NCTC11030) were capable for the enantioselective conversion of racemic Carvedilol. Immobilization technique enhanced the enantioselectivity of microorganisms and thus increased the enantiomeric purity of the drug. Excellent enantiomeric ratios (E) were found in reactions catalyzed by immobilized A. niger and E. coli with values 174.44 and 104.26, respectively. Triacylglycerol lipase from Aspergillus niger was also employed in this study as a biocatalyst which resulted in the product with 83.35% enantiomeric excess (ee) and E of 11.34 while the enzyme on immobilization has yielded 99.08% ee and 216.39 E. The conversion yield (C%) of the drug by free-enzyme was 57.42%, which was enhanced by immobilization to 90.51%. Hence, our results suggest that immobilized triacylglycerol lipase from A. niger (Lipase AP6) could be an efficient biocatalyst for the enantioselective resolution of racemic Carvedilol to (S)-(−)-Carvedilol with high enantiomeric purity followed by immobilized cultures of A. niger and E. coli.

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“…As interest in developing novel colon-targeted drug delivery systems for CRC has increased, insight into the presystemic biotransformation by the gut microbiota is fundamental. In vitro studies have shown that bacteria can metabolize celecoxib (14), potentially jeopardizing its anti-inflammatory effects. Additionally, whether celecoxib presence can modulate the host-microbiome crosstalk remains unresolved.…”

Section: Introductionmentioning

confidence: 99%

Short term supplementation of celecoxib shifted butyrate production on a simulated model of the gut microbial ecosystem and amelioratedin vitroinflammation

Hernandez-Sanabria

Heiremans

Arroyo

et al. 2019

Preprint

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Celecoxib has been demonstrated effective in the prevention and treatment of chronic inflammatory disorders through inhibition of altered cyclooxygenase-2 (COX-2) pathways. Despite the benefits for preventing colorectal cancer (CRC), continuous administration may increase risk of cardiovascular events. Understanding microbiome-drug-host interactions is fundamental for improving drug disposition and safety responses of colon-targeted formulations, but little information is available on the bidirectional interaction between individual microbiomes and celecoxib. Here we conducted in vitro batch incubations of faecal microbiota to evaluate the short-term impact of celecoxib on activity and composition of colon bacterial communities. Celecoxib-exposed microbiota shifted metabolic activity and community composition, whereas total transcriptionally active bacterial population was not significantly changed. Butyrate production decreased by 50% in a donor-dependent manner, suggesting that celecoxib impacts in vitro fermentation. Microbiota-derived acetate has been associated with inhibition of cancer markers and our results suggest uptake of acetate for bacterial functions when celecoxib was supplied, which potentially favoured bacterial competition for acetyl-CoA. We further assessed whether colon microbiota modulates anti-inflammatory efficacy of celecoxib using both a simplified inflammation model, and a novel in vitro simulation of the enterohepatic metabolism. Celecoxib was responsible for only 5% of the variance in bacterial community composition but celecoxib-exposed microbiota preserved barrier function and decreased concentrations of IL-8 and CXCL16 in a donor-dependent manner in our two cell models simulating inflammatory milieu in the gut. Our results suggest that celecoxib-microbiome-host interactions may not only elicit adaptations in community composition but also in microbiota functionality and may need to be considered for guaranteeing efficient COX-2 inhibition.IMPORTANCEAs inter-individual changes in the microbiome composition and functionality may be a confounder on pharmacotherapy, we obtained mechanistic understanding on how short-term celecoxib exposure impacts the functional activities of colon communities. Celecoxib-exposed microbiota shifted metabolic activity without impacting numbers of total active bacteria, but only community composition. Thus, increased relative abundance of particular genera during celecoxib supplementation may just indicate changes in maintenance energy. Focus on the influence of acetyl-CoA on cancer cells and verifying whether changes in acetate:propionate:butyrate ratios rather than in taxonomic diversity can be used as markers of decreased inflammation may be the next frontiers for predicting successful NSAID therapy, and ultimately for developing microbiome-based therapies.

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Biotransformation of Celecoxib Using Microbial Cultures

Cited by 20 publications

References 38 publications

Celecoxib does not alter intestinal microbiome in a longitudinal diet-controlled study

Celecoxib does not alter intestinal microbiome in a longitudinal diet-controlled study

Enantioselective Resolution of (R,S)-Carvedilol to (S)-(−)-Carvedilol by Biocatalysts

Short term supplementation of celecoxib shifted butyrate production on a simulated model of the gut microbial ecosystem and amelioratedin vitroinflammation

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