Abstract
Background
Recent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention.
Methods
We investigated the associations among gut microbiota, diet, and hepatic fat fraction (HFF) in 107 adolescents. Magnetic resonance imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires. We examined the association between gut microbiota alpha diversity and HFF, and assessed the predictive accuracy for HFF of (1) taxonomic composition, (2) dietary intake, (3) demographic and comorbid conditions, and (4) the combination of these.
Results
Lower alpha diversity was associated with higher HFF (β=−0.19, 95% confidence interval (CI) −0.36, −0.02). The selected taxa explained 17.7% (95% CI: 16.0–19.4%) of the variation in HFF. The combination of two of these taxa, Bilophila and Paraprevotella, with dietary intake of monounsaturated fatty acids and BMI z-scores explained 32.0% (95% CI: 30.3–33.6%) of the variation in HFF.
Conclusion
The gut microbiota is associated with HFF in adolescents and may be useful to help identify youth who would be amenable to gut microbiota-based interventions.
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References
Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10:686–690.
Bellentani S, Marino M. Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 2009;8:S4–S8.
Ali R, Cusi K. New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD). Ann Med 2009;41:265–278.
DeVore S, Kohli R, Lake K et al. A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. J Pediatr Gastroenterol Nutr 2013;57:119–123.
Boursier J, Diehl AM. Implication of Gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog 2015;11:e1004559.
Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016;13:412–425.
Finelli C, Tarantino G. Is there any consensus as to what diet or lifestyle approach is the right one for NAFLD patients. J Gastrointestin Liver Dis 2012;21:293–302.
Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 2015;11:577.
Tarantino G, Finelli C. Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease. Future Microbiol 2015;10:889–902.
Hussain HK, Chenevert TL, Londy FJ et al. Hepatic fat fraction: MR imaging for quantitative measurement and display—early experience. Radiology 2005;237:1048–1055.
Hussain HK, Oral EA, Rohrer S et al. Validation of hepatic fat quantified on 3 T MRI via histopathologic correlation in patients with non-alcoholic steatohepatitis. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson Med Sci Meet Exhib 16 2008;713.
Rastogi R, Gupta S, Garg B, Vohra S, Wadhawan M, Rastogi H. Comparative accuracy of CT, dual-echo MRI and MR spectroscopy for preoperative liver fat quantification in living related liver donors. Indian J Radiol Imaging 2016;26:5–14.
Block G, Murphy M, Roullet J, Wakimoto P Pilot validation of a FFQ for children 8-10 years. Fourth International Conference on Dietary Assessment Methods, Tucson, AZ, USA, 2000.
Crume TL, Scherzinger A, Stamm E et al. The long-term impact of intrauterine growth restriction in a diverse US cohort of children: The EPOCH study. Obesity 2014;22:608–615.
Centers for Disease Control and Prevention SAS Program (ages 0 to<20 years) ∣ Resources ∣ Growth Chart Training ∣ Nutrition ∣ DNPAO ∣ CDC [Internet]. Growth Chart Train (cited 6 Jan 2017) https://www.cdc.gov/nccdphp/dnpao/growthcharts/resources/sas.htm.
CDC Defining Childhood Overweight & Obesity [Internet] (cited 14 Mar 2017) https://www.cdc.gov/obesity/childhood/defining.html.
Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) Anthropometry procedures manual [Internet], 2007 (cited 8 Dec 2017) https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an.pdf.
Crume TL, Ogden L, Daniels S, Hamman RF, Norris JM, Dabelea D. The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: The EPOCH Study. J Pediatr 2011;158:941–946.
R Core Team R: A language and environment for statistical computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing, 2016 https://www.R-project.org/.
Caporaso JG, Kuczynski J, Stombaugh J et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010;7:335–336.
DeSantis TZ, Hugenholtz P, Larsen N et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 2006;72:5069–5072.
Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010;26:2460–2461.
Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. UniFrac: an effective distance metric for microbial community comparison. ISME J 2011;5:169.
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012;486:207–214.
Friedman J, Hastie T, Tibshirani R. Sparse inverse covariance estimation with the graphical lasso. Biostatistics 2008;9:432–441.
Zhu L, Baker SS, Gill C et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 2013;57:601–609.
Del Chierico F, Nobili V, Vernocchi P et al. Gut microbiota profiling of pediatric NAFLD and obese patients unveiled by an integrated meta-omics based approach. Hepatology 2016;65:451–464.
Sze MA, Schloss PD. Looking for a signal in the noise: revisiting obesity and the microbiome. mBio 2016;7:e01018–16.
Poeta M, Pierri L, Vajro P. Gut–liver axis derangement in non-alcoholic fatty liver disease. Children 2017;4:66.
Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the Gut microbiome. Curr Opin Gastroenterol 2014;30:332–338.
Hardison WG. Hepatic taurine concentration and dietary taurine as regulators of bile acid conjugation with taurine. Gastroenterology 1978;75:71–75.
Devkota S, Wang Y, Musch M et al. Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10−/− mice. Nature 2012;487:104–108.
O’Keefe SJD, Li JV, Lahti L et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun 2015;6:6342.
Wu GD, Chen J, Hoffmann C et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334:105–108.
David LA, Maurice CF, Carmody RN et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559–563.
Konikoff T, Gophna U. Oscillospira: a central, enigmatic component of the human gut microbiota. Trends Microbiol 2016;24:523–524.
Yatsunenko T, Rey FE, Manary MJ et al, Human gut microbiome viewed across age and geography. Nature [Internet], 2012 (cited 14 Apr 2014) http://www.nature.com/doifinder/10.1038/nature11053.
Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 2014;588:4223–4233.
Byers T. Food frequency dietary assessment: how bad is good enough? Am J Epidemiol 2001;154:1087–1088.
Maier TV, Lucio M, Lee LH et al. Impact of dietary resistant starch on the human gut microbiome, Metaproteome, and Metabolome. MBio 2017;8:e01343–17.
Statement of financial support
The EPOCH study was funded by grant R01 DK068001 (PI: D.D.) from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK).
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Stanislawski, M.A., Lozupone, C.A., Wagner, B.D. et al. Gut microbiota in adolescents and the association with fatty liver: the EPOCH study. Pediatr Res 84, 219–227 (2018). https://doi.org/10.1038/pr.2018.32
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DOI: https://doi.org/10.1038/pr.2018.32
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