Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency
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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.
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Coriobacteriaceae and Erysipelotrichaceae have previously been linked to obesity and lipid, primarily cholesterol, metabolism.
“Coriobacteriaceae and Erysipelotrichaceae – previously linked to obesity and lipid, primarily cholesterol, metabolism [43], [44], [45]”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [44]
Increased levels of Coriobacteriaceae and Erysipelotrichaceae have been associated previously with changes in hepatic and lipid metabolism in humans and various rodent species.
“These increased levels have been associated previously with changes in hepatic and lipid metabolism in humans and various rodent species [44], [45], [53], [54], [55].”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [44]
The observed changes to Coriobacteriaceae and Erysipelotrichaceae did not acutely impact lipid metabolism.
“suggesting that the observed changes to Coriobacteriaceae and Erysipelotrichaceae – previously linked to obesity and lipid, primarily cholesterol, metabolism [43], [44], [45] – did not acutely impact lipid metabolism.”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [44]
Levels of Erysipelotrichaceae positively correlate with changes in liver fat following a 2-month long dietary choline manipulation.
“levels of the latter positively correlate with changes in liver fat following a 2-month long dietary choline manipulation [44].”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [44]
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- Authors
- Spencer, M. D., Hamp, T. J., Reid, R. W., Fischer, L. M., Zeisel, S. H., & Fodor, A. A.
- Affiliations
- University of North Carolina at Charlotte (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Fodor, Anthony A.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 140
- Issue
- 3
- Pages
- 976-986
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3049827
- OpenAlex
- W2147163488
- Cited by
- 593
- References
- 53
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 26 · 2023: 37 · 2022: 35 · 2021: 46 · 2020: 59 · 2019: 52 · 2018: 63 · 2017: 41 · 2016: 37 · 2015: 37 · 2014: 45 · 2013: 37 · 2012: 27
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK055865, DK-056350, DK055865, P30DK056350)
- National Institute of Environmental Health Sciences (P30ES010126)
- National Center for Research Resources (RR00046, M01RR000046)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, choline deficiency, gut microbiota, hepatic lipid accumulation, Gammaproteobacteria, bacterial biomarkers, single nucleotide polymorphisms, host-microbe interactions, metabolic disorders
- MeSH terms
- Adult, Choline Deficiency, Fatty Liver, Feces, Female, Humans, Magnetic Resonance Imaging, North Carolina, Promoter Regions, Genetic, Risk Factors, Time Factors, Cluster Analysis, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Ribotyping, Principal Component Analysis, Gastrointestinal Tract, Phosphatidylethanolamine N-Methyltransferase, Metagenome, Non-alcoholic Fatty Liver Disease
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