Background and aims: Choline has been shown to exert atherogenic effects in Apoe- /- and Ldlr- /-mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the... Show moreBackground and aims: Choline has been shown to exert atherogenic effects in Apoe- /- and Ldlr- /-mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism. Methods: Female APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks. Results: Interestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size. Conclusions: While choline and butyrate have been reported to oppositely modulate atherosclerosis development in Apoe-/-and Ldlr-/-mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice. Show less
Background and aimsCholine has been shown to exert atherogenic effects in Apoe−/− and Ldlr−/− mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the... Show moreBackground and aimsCholine has been shown to exert atherogenic effects in Apoe−/− and Ldlr−/− mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism.MethodsFemale APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks.ResultsInterestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size.ConclusionsWhile choline and butyrate have been reported to oppositely modulate atherosclerosis development in Apoe−/− and Ldlr−/− mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice. Show less
In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest... Show moreIn recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case-control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67-75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62-80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 mu M, Wilcoxonp < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77,p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections. Show less
