Dataset Information

L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.

ABSTRACT: BACKGROUND:l-Carnitine, an abundant nutrient in red meat, accelerates atherosclerosis in mice via gut microbiota-dependent formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO) via a multistep pathway involving an atherogenic intermediate, ?-butyrobetaine (?BB). The contribution of ?BB in gut microbiota-dependent l-carnitine metabolism in humans is unknown. METHODS:Omnivores and vegans/vegetarians ingested deuterium-labeled l-carnitine (d3-l-carnitine) or ?BB (d9-?BB), and both plasma metabolites and fecal polymicrobial transformations were examined at baseline, following oral antibiotics, or following chronic (?2 months) l-carnitine supplementation. Human fecal commensals capable of performing each step of the l-carnitine??BB?TMA transformation were identified. RESULTS:Studies with oral d3-l-carnitine or d9-?BB before versus after antibiotic exposure revealed gut microbiota contribution to the initial 2 steps in a metaorganismal l-carnitine??BB?TMA?TMAO pathway in subjects. Moreover, a striking increase in d3-TMAO generation was observed in omnivores over vegans/vegetarians (>20-fold; P = 0.001) following oral d3-l-carnitine ingestion, whereas fasting endogenous plasma l-carnitine and ?BB levels were similar in vegans/vegetarians (n = 32) versus omnivores (n = 40). Fecal metabolic transformation studies, and oral isotope tracer studies before versus after chronic l-carnitine supplementation, revealed that omnivores and vegans/vegetarians alike rapidly converted carnitine to ?BB, whereas the second gut microbial transformation, ?BB?TMA, was diet inducible (l-carnitine, omnivorous). Extensive anaerobic subculturing of human feces identified no single commensal capable of l-carnitine?TMA transformation, multiple community members that converted l-carnitine to ?BB, and only 1 Clostridiales bacterium, Emergencia timonensis, that converted ?BB to TMA. In coculture, E. timonensis promoted the complete l-carnitine?TMA transformation. CONCLUSION:In humans, dietary l-carnitine is converted into the atherosclerosis- and thrombosis-promoting metabolite TMAO via 2 sequential gut microbiota-dependent transformations: (a) initial rapid generation of the atherogenic intermediate ?BB, followed by (b) transformation into TMA via low-abundance microbiota in omnivores, and to a markedly lower extent, in vegans/vegetarians. Gut microbiota ?BB?TMA/TMAO transformation is induced by omnivorous dietary patterns and chronic l-carnitine exposure. TRIAL REGISTRATION:ClinicalTrials.gov NCT01731236. FUNDING:NIH and Office of Dietary Supplements grants HL103866, HL126827, and DK106000, and the Leducq Foundation.

SUBMITTER: Koeth RA

PROVIDER: S-EPMC6307959 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.

Koeth Robert A RA Lam-Galvez Betzabe Rachel BR Kirsop Jennifer J Wang Zeneng Z Levison Bruce S BS Gu Xiaodong X Copeland Matthew F MF Bartlett David D Cody David B DB Dai Hong J HJ Culley Miranda K MK Li Xinmin S XS Fu Xiaoming X Wu Yuping Y Li Lin L DiDonato Joseph A JA Tang W H Wilson WHW Garcia-Garcia Jose Carlos JC Hazen Stanley L SL

The Journal of clinical investigation 20181210 1

<h4>Background</h4>l-Carnitine, an abundant nutrient in red meat, accelerates atherosclerosis in mice via gut microbiota-dependent formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO) via a multistep pathway involving an atherogenic intermediate, γ-butyrobetaine (γBB). The contribution of γBB in gut microbiota-dependent l-carnitine metabolism in humans is unknown.<h4>Methods</h4>Omnivores and vegans/vegetarians ingested deuterium-labeled l-carnitine (d3-l-carnitine) or γBB (d9-γBB ...[more]

PMID: 30530985

Similar Datasets

Project description:Obligate bacterial symbionts alter the diets of host animals in numerous ways, but the ecological roles of facultative bacterial residents that colonize insect guts remain unclear. Carabid beetles are a common group of beneficial insects appreciated for their ability to consume insect prey and seeds, but the contributions of microbes to diet diversification in this and similar groups of facultative granivores are largely unknown.Using 16S rRNA gene clone libraries and terminal restriction fragment (tRF) length polymorphism analyses of these genes, we examined the bacterial communities within the guts of facultatively granivorous, adult Harpalus pensylvanicus (Carabidae), fed one of five dietary treatments: 1) an untreated Field population, 2) Seeds with antibiotics (seeds were from Chenopodium album), 3) Seeds without antibiotics, 4) Prey with antibiotics (prey were Acheta domesticus eggs), and 5) Prey without antibiotics. The number of seeds and prey consumed by each beetle were recorded following treatment. Harpalus pensylvanicus possessed a fairly simple gut community of approximately 3-4 bacterial operational taxonomic units (OTU) per beetle that were affiliated with the Gammaproteobacteria, Bacilli, Alphaproteobacteria, and Mollicutes. Bacterial communities of the host varied among the diet and antibiotic treatments. The field population and beetles fed seeds without antibiotics had the closest matching bacterial communities, and the communities in the beetles fed antibiotics were more closely related to each other than to those of the beetles that did not receive antibiotics. Antibiotics reduced and altered the bacterial communities found in the beetle guts. Moreover, beetles fed antibiotics ate fewer seeds, and those beetles that harbored the bacterium Enterococcus faecalis consumed more seeds on average than those lacking this symbiont.We conclude that the relationships between the bacterium E. faecalis and this factultative granivore's ability to consume seeds merit further investigation, and that facultative associations with symbiotic bacteria have important implications for the nutritional ecology of their hosts.

Project description:Background Algivorous sea urchins can obtain energy from a diet of a single algal species, which may result in consequent changes in their gut microbe assemblies and association networks. Methods To ascertain whether such changes are led by specific microbes or limited to a specific region in the gut, we compared the microbial assembly in the three major gut regions of the sea urchin Tripneustes gratilla elatensis when fed a mono-specific algal diet of either Ulva fasciata or Gracilaria conferta, or an algal-free diet. DNA extracts from 5 to 7 individuals from each diet treatment were used for Illumina MiSeq based 16S rRNA gene sequencing (V3–V4 region). Niche breadth of each microbe in the assembly was calculated for identification of core, generalist, specialist, or unique microbes. Network analyzers were used to measure the connectivity of the entire assembly and of each of the microbes within it and whether it altered with a given diet or gut region. Lastly, the predicted metabolic functions of key microbes in the gut were analyzed to evaluate their potential contribution to decomposition of dietary algal polysaccharides. Results Sea urchins fed with U. fasciata grew faster and their gut microbiome network was rich in bacterial associations (edges) and networking clusters. Bacteroidetes was the keystone microbe phylum in the gut, with core, generalist, and specialist representatives. A few microbes of this phylum were central hub nodes that maintained community connectivity, while others were driver microbes that led the rewiring of the assembly network based on diet type through changes in their associations and centrality. Niche breadth agreed with microbes' richness in genes for carbohydrate active enzymes and correlated Bacteroidetes specialists to decomposition of specific polysaccharides in the algal diets. Conclusions The dense and well-connected microbial network in the gut of Ulva-fed sea urchins, together with animal's rapid growth, may suggest that this alga was most nutritious among the experimental diets. Our findings expand the knowledge on the gut microbial assembly in T. gratilla elatensis and strengthen the correlation between microbes’ generalism or specialism in terms of occurrence in different niches and their metabolic arsenal which may aid host nutrition. Supplementary Information The online version contains supplementary material available at 10.1186/s42523-021-00140-1.

Dataset Information

L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.

Publications

l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure