Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency.

TitleAssociation between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency.
Publication TypeJournal Article
Year of Publication2011
AuthorsSpencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA
JournalGastroenterology
Volume140
Issue3
Pagination976-86
Date Published2011 Mar
ISSN1528-0012
KeywordsAdult, Choline Deficiency, Cluster Analysis, Fatty Liver, Feces, Female, Gastrointestinal Tract, Genetic Predisposition to Disease, Humans, Magnetic Resonance Imaging, Metagenome, Non-alcoholic Fatty Liver Disease, North Carolina, Phosphatidylethanolamine N-Methyltransferase, Polymorphism, Single Nucleotide, Principal Component Analysis, Promoter Regions, Genetic, Ribotyping, Risk Assessment, Risk Factors, Time Factors
Abstract

<p><b>BACKGROUND & AIMS: </b>Nonalcoholic fatty liver disease affects up to 30% of the US population, but the mechanisms underlying this condition are incompletely understood. We investigated how diet standardization and choline deficiency influence the composition of the microbial community in the human gastrointestinal tract and the development of fatty liver under conditions of choline deficiency.</p><p><b>METHODS: </b>We performed a 2-month inpatient study of 15 female subjects who were placed on well-controlled diets in which choline levels were manipulated. We used 454-FLX pyrosequencing of 16S ribosomal RNA bacterial genes to characterize microbiota in stool samples collected over the course of the study.</p><p><b>RESULTS: </b>The compositions of the gastrointestinal microbial communities changed with choline levels of diets; each individual's microbiome remained distinct for the duration of the experiment, even though all subjects were fed identical diets. Variations between subjects in levels of Gammaproteobacteria and Erysipelotrichi were directly associated with changes in liver fat in each subject during choline depletion. Levels of these bacteria, change in amount of liver fat, and a single nucleotide polymorphism that affects choline were combined into a model that accurately predicted the degree to which subjects developed fatty liver on a choline-deficient diet.</p><p><b>CONCLUSIONS: </b>Host factors and gastrointestinal bacteria each respond to dietary choline deficiency, although the gut microbiota remains distinct in each individual. We identified bacterial biomarkers of fatty liver that result from choline deficiency, adding to the accumulating evidence that gastrointestinal microbes have a role in metabolic disorders.</p>

DOI10.1053/j.gastro.2010.11.049
Alternate JournalGastroenterology
PubMed ID21129376
PubMed Central IDPMC3049827
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
M01 RR000046 / RR / NCRR NIH HHS / United States
DK055865 / DK / NIDDK NIH HHS / United States
R01 DK055865 / DK / NIDDK NIH HHS / United States
P30 DK056350-10 / DK / NIDDK NIH HHS / United States
P30 DK056350-09S3 / DK / NIDDK NIH HHS / United States
P30 DK056350-09 / DK / NIDDK NIH HHS / United States
P30 DK056350-09S2 / DK / NIDDK NIH HHS / United States
R01 DK055865-10 / DK / NIDDK NIH HHS / United States
P30 DK056350 / DK / NIDDK NIH HHS / United States
DK056350 / DK / NIDDK NIH HHS / United States
P30 DK056350-09S1 / DK / NIDDK NIH HHS / United States
R01 DK055865-09 / DK / NIDDK NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States