Gastroenterology

Gastroenterology

Volume 140, Issue 3, March 2011, Pages 976-986
Gastroenterology

Basic—Alimentary Tract
Association Between Composition of the Human Gastrointestinal Microbiome and Development of Fatty Liver With Choline Deficiency

https://doi.org/10.1053/j.gastro.2010.11.049Get rights and content

Background & Aims

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.

Section snippets

Study Subjects

Healthy female subjects (n = 15), a subset of those enrolled in a National Institutes of Health–funded study (DK055865) investigating choline metabolism, were recruited to participate in a gut metagenomic study and provided informed consent (approved by the institutional review boards at the University of North Carolina at Chapel Hill and at the University of North Carolina at Charlotte). Inclusion was contingent on a good state of health, a body mass index of 18 to 34 kg/m2, and no history of

Experimental Design

Healthy adult female subjects (n = 15; Supplementary Table 1) were brought into the hospital and fed a prescribed experimental diet that included 3 dietary phases: (1) a standard research diet providing the current recommended level of choline, (2) a diet with very low choline, and (3) a diet that included significant levels of choline to restore subjects' choline levels (Figure 1). Stool samples were obtained at time points reflecting dietary changes (Figure 1), and the gut microbiome was

Discussion

Our study shows the importance of longitudinal experimental design and rigorous dietary control to identify changes in the gut microbiome that have potentially significant ramifications for human nutrition and health. We have verified previous findings8, 48 that gut microbial communities are distinctly individual and have shown that there is little generalized convergence between subjects on a common diet over a 2-month period (Figure 2). Although gut microbiota remained characteristically

Acknowledgments

The original data file containing all pyrosequences has been submitted to the Short Read Archive at the National Center for Biotechnology Information under accession no. SRA012606.2 (http://www.ncbi.nlm.nih.gov/Traces/sra_sub/sub.cgi?&m=submissions&s=defaults).

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by grants from the National Institutes of Health (DK055865 and DK056350) and the Clinical and Translational Research Center (RR00046).

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