scholarly journals The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

2021 ◽  
Author(s):  
Priscilla Day-Walsh ◽  
Emad Shehata ◽  
Shikha Saha ◽  
George M. Savva ◽  
Barbora Nemeckova ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Human Colon ◽  
Human Studies ◽  
Bacterial Strains ◽  
Increased Risk ◽  
Carnitine Metabolism ◽  
Registration Number ◽  
Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

Bioconversion by gut microbiota of predigested mango (Mangifera indica L) ‘Ataulfo’ peel polyphenols assessed in a dynamic (TIM-2) in vitro model of the human colon

2021 ◽  
Vol 139 ◽  
pp. 109963
Author(s):  
Sonia G. Sáyago-Ayerdi ◽  
Koen Venema ◽  
Maria Tabernero ◽  
Beatriz Sarriá ◽  
L. Laura Bravo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
In Vitro Model ◽  
Mangifera Indica ◽  
Human Colon ◽  
Vitro Model

Comparative methods for fecal sample storage to preserve gut microbial structure and function in an in vitro model of the human colon

2020 ◽  
Vol 104 (23) ◽  
pp. 10233-10247
Author(s):  
Charlotte Deschamps ◽  
Elora Fournier ◽  
Ophélie Uriot ◽  
Frédérique Lajoie ◽  
Cécile Verdier ◽  
...  
Keyword(s):  
Fecal Sample ◽  
In Vitro Model ◽  
Human Colon ◽  
Structure And Function ◽  
Comparative Methods ◽  
Sample Storage ◽  
Microbial Structure ◽  
Vitro Model ◽  
And Function

scholarly journals The Niemann-Pick C1 Like 1 (NPC1L1) Inhibitor Ezetimibe Improves Metabolic Disease Via Decreased Liver X Receptor (LXR) Activity in Liver of Obese Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2810-2819 ◽  
Author(s):  
Taichi Sugizaki ◽  
Mitsuhiro Watanabe ◽  
Yasushi Horai ◽  
Nao Kaneko-Iwasaki ◽  
Eri Arita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Insulin Signaling ◽  
Metabolic Diseases ◽  
In Vitro Study ◽  
Liver X Receptor ◽  
Gene Expressions ◽  
The Metabolic Syndrome ◽  
Increased Risk

Dyslipidemic patients with diabetes mellitus, including metabolic syndrome, are at increased risk of coronary heart disease. It has been reported that ezetimibe, a cholesterol absorption inhibitor, improves metabolic diseases in mice and humans. However, the underlying mechanism has been unclear. Here we explored the effects of ezetimibe on lipid and glucose homeostasis. Male KK-Ay mice were fed a high-fat diet, which is the mouse model of metabolic syndrome, with or without ezetimibe for 14 weeks. Ezetimibe improved dyslipidemia, steatosis, and insulin resistance. Ezetimibe decreased hepatic oxysterols, which are endogenous agonists of liver X receptor (LXR), to decrease hepatic lipogenic gene expressions, especially in stearoyl-CoA desaturase-1 (SCD1), leading to a remarkable reduction of hepatic oleate content that would contribute to the improvement of steatosis by reducing triglycerides and cholesterol esters. Simultaneously, hepatic β-oxidation, NADPH oxidase and cytochrome P450 2E1 (CYP2E1) were reduced, and thus reactive oxygen species (ROS) and inflammatory cytokines were also decreased. Consistent with these changes, ezetimibe diminished c-Jun N-terminal kinase (JNK) phosphorylation and improved insulin signaling in the liver. In vitro study using primary hepatocytes obtained from male SD rats, treated with oleate and LXR agonist, showed excess lipid accumulation, increased oxidative stress and impaired insulin signaling. Therefore, in obese subjects, ezetimibe reduces hepatic LXR activity by reducing hepatic oxysterols to lower hepatic oleate content. This improves steatosis and reduces oxidative stress, and this reduction improves insulin signaling in the liver. These results provide insight into pathogenesis and strategies for treatment of the metabolic syndrome.

Influence of Bacillus subtilis C-3102 on microbiota in a dynamic in vitro model of the gastrointestinal tract simulating human conditions

2012 ◽  
Vol 3 (3) ◽  
pp. 229-236 ◽  
Author(s):  
M. Hatanaka ◽  
Y. Nakamura ◽  
A.J.H. Maathuis ◽  
K. Venema ◽  
I. Murota ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Gastrointestinal Tract ◽  
In Vitro Model ◽  
Germination Rate ◽  
Human Colon ◽  
Micro Array ◽  
Vitro Model ◽  
Oral Doses ◽  
The Impact

Survival and germination rate of Bacillus subtilis C-3102 spores were investigated in a stomach and small intestine model (TIM-1), while the impact of C-3102 cells that had passed through TIM-1 on human colon microbiota was evaluated in a model of the large intestine (TIM-2). The survival of C-3102 spores in TIM-1 was 99%; 8% of the spores had germinated. Effluent of TIM-1 was subsequently introduced into TIM-2 and a micro-array platform was employed to assess changes in the microbiota composition. The effluent, which contained germinated C-3102 cells, increased some Bifidobacterium species and decreased some Clostridium groups. These changes were greater compared to those obtained by adding C-3102 spores directly to TIM-2. The present study suggests that oral doses of B. subtilis C-3102 spores have the potential to modulate the human colon microbiota. This effect may be caused by germination of the spores in the gastrointestinal tract.

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