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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Bioinformatics and Genomics, University of North Carolina, Charlotte, North Carolina 28223, USA.
Melanie D
MD
Spencer
Timothy J
TJ
Hamp
Robert W
RW
Reid
Leslie M
LM
Fischer
Steven H
SH
Zeisel
Anthony A
AA
Fodor
D000328:Adult; D002796:Choline Deficiency / Q000150:complications* / Q000235:genetics / Q000382:microbiology; D016000:Cluster Analysis; D005234:Fatty Liver / Q000175:diagnosis / Q000209:etiology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D054892:Metagenome; D065626:Non-alcoholic Fatty Liver Disease; D009657:North Carolina; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic; D021521:Ribotyping; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase