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Metformin (Glucophage) Biodegradation: Insights from Microbiome and Biochemical Analyses

2021· article· en· W3166477354 on OpenAlexaff
Ashley Robinson, Lambros J. Tassoulas, Betsy Martinez Vaz, Kelly G. Aukema, Lawrence P. Wackett

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsSaint Paul University
FundersU.S. Department of Agriculture
KeywordsMetforminMetagenomicsMicrobiomeBiologyMicrobiologyChemistryBiochemistryBiotechnologyBioinformaticsGene

Abstract

fetched live from OpenAlex

Metformin is the most prescribed type 2 diabetes medication in the United States and in many countries worldwide. In diabetes patients, this drug has been shown to alter the gut microbiome resulting in improved glucose metabolism. More recently, metformin has been proposed to have anti‐aging and antiviral properties making the drug a potential candidate to treat other health conditions. Metformin and its proposed “dead‐end” product, guanylurea, are not fully metabolized by humans and enter municipal wastewater where they cannot be removed through conventional water treatment processes. These compounds have been detected in surface waters around the world and are currently considered emerging pollutants. This study examined a bacterial consortium enriched from activated sludge which demonstrated the ability to utilize metformin as a sole source of nitrogen, as well as to degrade metformin to its transformation product, guanylurea. Metagenomic sequencing yielded an 18 Mb assembly distributed over 7,440 contigs with an average GC content of 64%. 16S rRNA analysis suggested the presence of Sphingopyxis, Pseudomonas mendocina, Microbacterium, and Mesorhizhobium species within the consortia. Bioinformatic analysis led to the identification of three relevant enzymes involved in metformin metabolism: guanylurea hydrolase, carboxyguanidine deiminase, and allophanate hydrolase. Biochemical studies revealed that these proteins catalyze the degradation of guanylurea to ammonia and carbon dioxide. Protein sequence analyses and structural modeling studies are currently in progress to identify a candidate gene(s) encoding the enzyme initiating the metabolism of metformin. This research presents the first evidence for a biochemical pathway associated with the microbial degradation of guanylurea. Significantly, it also advances understanding of the microbial capacity for metformin biodegradation. These findings could lead to the development of practical biotechnological applications to improve water treatment processes and provide insight into the effects of metformin on human microbiome metabolism.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.063
GPT teacher head0.364
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2021
Admission routes1
Has abstractyes

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