Identification of choline-degrading bacteria from healthy human feces and used for screening of trimethylamine (TMA)-lyase inhibitors

Heng, Xing; Liu, Wugao; Chu, Weihua

doi:10.1016/j.micpath.2020.104658

Cited by 23 publications

(12 citation statements)

References 23 publications

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“…Consistent with the study of Li, JV et al, our results suggested that PAGln was signi cantly correlated with Klebsiella [52]. Klebsiella is widely believed to be a pathogenic bacterium and a strain with the TMA gene [53][54][55]. TMA is an essential precursor of the gut microbiota metabolite TMAO, which has been found to promote thrombosis via increasing platelet reactivity [56].…”

Section: Discussionsupporting

confidence: 89%

Elevated Circulating Levels of Phenylacetylglutamine in Stroke Patients With T2D Are Linked to Specific Gut Microbiota

Xia

Wei

Huang

et al. 2022

Preprint

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Background Type 2 diabetes (T2D) aggravates the injury of ischemic stroke (IS). The gut microbiota-related metabolite phenylacetylglutamine (PAGln) has been shown to elevate in plasma of patients with T2D and promote thrombosis. However, the alterations of gut microbiota and PAGln levels in stroke patients with T2D remain unclear. Therefore, our study aimed to explore the differences in gut microbiota and its metabolite PAGln between IS patients with and without T2D.Methods In our study, 35 IS with T2D (IS-T2D group), 50 IS patients without T2D (IS group), and 29 healthy controls (HC group) were recruited from December 2019 to December 2020. Fecal samples were collected and analyzed using 16S rRNA high throughput sequencing, and plasma samples were subjected to targeted metabolomics to detect metabolite PAGln. Plasma PAGln levels of rats with transplantation of fecal microbes from patients were assessed. Results Our results showed that compared with the IS group, the relative abundances of Proteobacteria, Verrucomicrobiota, Enterobacteriaceae, and Klebsiella were enriched in the IS-T2D group. The plasma PAGln levels in IS-T2D patients were significantly higher than those in IS patients. Correlation analysis showed that plasma PAGln levels were significantly correlated with Enterobacteriaceae, Verrucomicrobiota, and Klebsiella, which were enriched in IS-T2D patients. Further studies demonstrated that plasma PAGln levels were positively correlated with the concentration of NETs, and NETs levels were increased in a dose-dependent manner according to PAGln levels. In addition, the rats transplanted with fecal microbes from IS-T2D patients developed more severe brain injury and higher plasma PAGln levels compared to the rats transplanted with fecal microbes from IS patients. Moreover, a prediction model based on the differential relative abundances of microbiota, plasma PAGln levels, and NETs levels was constructed to discriminate IS-T2D from stroke patients. Conclusions Our results suggest that the gut microbiota is imbalanced and its metabolite PAGln levels are increased in stroke patients with T2D, and T2D potentially aggravates stroke injury via an inflammatory response, which is associated with gut microbiota and its metabolite PAGln modulation.

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Section: Discussionsupporting

confidence: 89%

Elevated Circulating Levels of Phenylacetylglutamine in Stroke Patients With T2D Are Linked to Specific Gut Microbiota

Xia

Wei

Huang

et al. 2022

Preprint

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“…High-throughput inhibitor screening studies have demonstrated their utility for quickly identifying synthetic CutC/D inhibitors [ 18 ], and these types of approaches could be used to narrow down a vast array of hundreds or thousands of potential phytochemicals to a few promising candidate compounds with inhibitory activity to be subsequently tested in vivo. In this sense, Heng et al have recently proposed a methodology to identify TMA-lyase-containing bacteria, isolate them, and use them to screen for potential compounds that inhibit choline metabolism to TMA in silico and in vitro [ 19 ]. In their approach, in silico docking studies suggested a few phytochemicals as potential TMA-lyase inhibitors, but the in silico approach alone does not take into account the diversity of bacteria in the gut (i.e., interaction between bacteria).…”

Section: Introductionmentioning

confidence: 99%

Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

et al. 2021

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Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80–90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.

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“…High throughput inhibitor screening studies have demonstrated their utility for quickly identifying synthetic CutC/D inhibitors [18], and these type of approaches could be used to narrow down a vast array of hundreds or thousands of potential phytochemicals to a few promising candidate compounds with inhibitory activity to be subsequently tested in vivo. In this sense, Heng et al have recently proposed a methodology to identify TMA-lyase containing bacteria, isolate them, and use them to screen for potential compounds that inhibit choline metabolism to TMA in silico and in vitro [19]. In their approach, in silico docking studies suggested a few phytochemicals as potential TMA-lyase inhibitors, but the in vivo approach only does not take into account the diversity of bacteria in the gut (i.e., interaction between bacteria).…”

Section: Introductionmentioning

confidence: 99%

Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Iglesias‐Carres

Essenmacher

Racine

et al. 2021

Preprint

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Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

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Identification of choline-degrading bacteria from healthy human feces and used for screening of trimethylamine (TMA)-lyase inhibitors

Cited by 23 publications

References 23 publications

Elevated Circulating Levels of Phenylacetylglutamine in Stroke Patients With T2D Are Linked to Specific Gut Microbiota

Elevated Circulating Levels of Phenylacetylglutamine in Stroke Patients With T2D Are Linked to Specific Gut Microbiota

Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

Development of a High Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation

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