Association Between Composition of the Human Gastrointestinal Microbiome and Development of Fatty Liver With Choline Deficiency

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 140; no. 3; pp. 976 - 986
• Main Authors: Spencer, Melanie D., Hamp, Timothy J., Reid, Robert W., Fischer, Leslie M., Zeisel, Steven H., Fodor, Anthony A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2011
• Subjects: Adult; Bacteria; Choline Deficiency - complications; Choline Deficiency - genetics; Choline Deficiency - microbiology; Choline Metabolism; Cluster Analysis; Fatty Liver - diagnosis; Fatty Liver - etiology; Fatty Liver - microbiology; Feces - microbiology; Female; Gastroenterology and Hepatology; Gastrointestinal Tract - microbiology; Genetic Predisposition to Disease; Hepatic Steatosis; Humans; Magnetic Resonance Imaging; Metagenome; Non-alcoholic Fatty Liver Disease; North Carolina; Phosphatidylcholine; Phosphatidylethanolamine N-Methyltransferase - genetics; Polymorphism, Single Nucleotide; Principal Component Analysis; Promoter Regions, Genetic; Ribotyping; Risk Assessment; Risk Factors; Time Factors; North Carolina; OTU; SNP; Hepatic Steatosis; MRI; LF/SF; Phosphatidylcholine; Bacteria; ARISA; Choline Metabolism; PCR; PCA; RDP; magnetic resonance imaging; single nucleotide polymorphism; operational taxonomic unit; principal components analysis; liver fat to spleen fat ratio; Ribosomal Database Project; automated ribosomal intergenic sequence analysis; polymerase chain reaction
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2010.11.049

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. 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. 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. 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.