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Mayne, J.

Publications and source records attributed to Mayne, J..

3 recordsLinked to original sources

An in vitro model maintaining taxon-specific functional activities of the gut microbiome

The gut microbiome is a new target for therapeutics. In vitro high-throughput culture models could provide time-and-cost saving solutions to discover microbiome responses to drugs. Unfortunately, there has been no report of in vitro models capable of maintaining functional and compositional profiles resembling the in vivo gut microbiome. Here, we developed and validated a high-throughput culturing model named Mipro to maintain individuals microbiomes. The Mipro model quintupled viable bacteria count while maintained the functional and compositional profiles of individuals gut microbiomes. Comparison of taxon-specific functions between pre -and-post culture microbiomes showed Pearsons correlation coefficient r of 0.83 {+/-} 0.03. Moreover, the Mipro model also exhibited a high degree of in vitro - in vivo correlation (Pearsons r of 0.68 {+/-} 0.09) in microbial responses to metformin in mice fed a high-fat diet. Mipro provides a highly simulated gut microbiome for high-throughput investigation of drug-microbiome interactions.

microbiology

RapidAIM: A culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs

The gut microbiome has been associated with a growing list of diseases. Drugs and other compounds can affect the microbiome, but our understanding of drug-induced changes in individual microbiomes is limited due to a lack of rapid and effective high-throughput assay methods. We developed an approach named Rapid Assay of Individual Microbiome (RapidAIM) to screen xenobiotics against individual microbiomes. RapidAIM was evaluated by testing 43 compounds against five individual microbiomes using a metaproteomic approach. We show that our workflow enables quantitative profiling of the microbiome. The tested compounds significantly affected overall microbiome abundance, microbiome composition and functional pathways at multiple taxonomic levels. The microbiome responses to berberine, metformin, diclofenac, fructooligosaccharide and most antibiotics were consistent among most individuals. Interestingly, most of our tested NSAIDs, statins, and histamine-2 blockers induced strong and individually distinct responses. Our workflow offers an effective solution to systematically study the effects of many different compounds on individual microbiomes.

microbiology

Therapeutic Targeting of Casein Kinase 1δ/ε in an Alzheimer's Disease Mouse Model

Sleep disturbances and memory impairment are common symptoms of Alzheimers disease (AD). Given that the circadian clock regulates sleep, hippocampal function, and neurodegeneration, it represents a therapeutic target against AD. Casein kinase 1{delta}/{varepsilon} (CK1{delta}/{varepsilon}) are clock regulators and overexpressed in AD brains, making them viable targets to improve sleep and cognition. We assessed the effects of a small molecule CK1{delta}/{varepsilon} inhibitor (PF-670462) in a cellular model of circadian clocks and in 3xTg-AD mice. Mass spectrometry-based proteomic analyses revealed that PF-670462 treatment in vitro upregulated multiple proteins that are downregulated in AD, while administration in 3xTg-AD mice reversed hippocampal proteomic alterations in diverse AD-associated and clock-regulated pathways, including synaptic plasticity and amyloid precursor protein processing. Furthermore, PF-670462 rescued working memory and normalized behavioural circadian rhythms in 3xTg-AD mice. Our study provides proof of concept for CK1{delta}/{varepsilon} inhibition and direct clock modulation against AD-related proteomic changes, memory impairment, and circadian disturbances.

biochemistry