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- Cheng, Liqin, et al.
(author)
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The protective role of commensal gut microbes and their metabolites against bacterial pathogens
- 2024
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In: Gut microbes. - : Taylor & Francis. - 1949-0976 .- 1949-0984. ; 16:1
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Journal article (peer-reviewed)abstract
- Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is a gold mine for bioactive compounds that protect the human body from pathogens. We used a multi-omics approach that integrated whole-genome sequencing (WGS) of 74 commensal gut microbiome isolates with metabolome analysis to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We evaluated differences in the functional potential of these selected isolates based on WGS annotation profiles. Furthermore, the top altered metabolites in co-culture supernatants of selected commensal gut microbiome isolates were identified including a series of dipeptides and examined for their ability to prevent the growth of various antibiotic-resistant bacteria. Our results provide compelling evidence that the gut microbiome produces metabolites, including the compound class of dipeptides that can potentially be applied for anti-infection medication, especially against antibiotic-resistant pathogens. Our established pipeline for the discovery and validation of bioactive metabolites from the gut microbiome as novel candidates for multidrug-resistant infections represents a new avenue for the discovery of antimicrobial lead structures.
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- Tsiara, Ioanna, et al.
(author)
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Immobilized Enzymes on Magnetic Beads for Separate Mass Spectrometric Investigation of Human Phase II Metabolite Classes
- 2023
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 95:33, s. 12565-12571
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Journal article (peer-reviewed)abstract
- The human body hasevolved to remove xenobiotics through a multistepclearance process. Non-endogenous metabolites are converted througha series of phase I and different phase II enzymes into compoundswith higher hydrophilicity. These compounds are important for diverseresearch fields such as toxicology, nutrition, biomarker discovery,doping control, and microbiome metabolism. One of the challenges inthese research fields has been the investigation of the two majorphase II modifications, sulfation and glucuronidation, and the correspondingunconjugated aglycon independently. We have now developed a new methodologyutilizing an immobilized arylsulfatase and an immobilized & beta;-glucuronidaseto magnetic beads for treatment of human urine samples. The enzymeactivities remained the same compared to the enzyme in solution. Theseparate mass spectrometric investigation of each metabolite classin a single sample was successfully applied to obtain the dietaryglucuronidation and sulfation profile of 116 compounds. Our new chemicalbiology strategy provides a new tool for the investigation of metabolitesin biological samples with the potential for broad-scale applicationin metabolomics, nutrition, and microbiome studies.
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