Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Ahluwalia, Vishwadeep ^a   Betrapally, Naga S ^b   Hylemon, Phillip B ^a   White, Melanie B ^a   Gillevet, Patrick M ^b   Unser, Ariel B ^a   Fagan, Andrew ^a   Daita, Kalyani ^a   Heuman, Douglas M ^a   Zhou, Huiping ^a   Sikaroodi, Masoumeh ^b   Bajaj, Jasmohan S ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b GEORGE MASON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; AGED; ASTROCYTE; BACTEROIDACEAE; BIOLOGICAL MODEL; BRAIN; BRAIN EDEMA; COGNITIVE DEFECT; COMPLICATION; DIAGNOSTIC IMAGING; DIFFUSION TENSOR IMAGING; DYSBIOSIS; ENTEROBACTERIACEAE; FEMALE; FIRMICUTES; HEPATIC ENCEPHALOPATHY; HUMAN; HYPERAMMONEMIA; INFLAMMATION; INTESTINE; INTESTINE FLORA; ISOLATION AND PURIFICATION; LIVER; LIVER CIRRHOSIS; MALE; MICROBIOLOGY; MIDDLE AGED; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PATHOLOGY; PATHOPHYSIOLOGY; PSYCHOLOGY;

ADULT; AGED; ASTROCYTES; BACTEROIDACEAE; BRAIN; BRAIN EDEMA; COGNITION DISORDERS; DIFFUSION TENSOR IMAGING; DYSBIOSIS; ENTEROBACTERIACEAE; FEMALE; FIRMICUTES; GASTROINTESTINAL MICROBIOME; HEPATIC ENCEPHALOPATHY; HUMANS; HYPERAMMONEMIA; INFLAMMATION; INTESTINES; LIVER; LIVER CIRRHOSIS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; NEUROIMAGING;

EID: 84971264719     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep26800     Document Type: Article

References (45)

1. Vilstrup, H. et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 60, 715-735, doi: 10.1002/hep.27210 (2014).
2. Bajaj, J. S. et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. Journal of hepatology 60, 940-947, doi: 10.1016/j.jhep.2013.12.019 (2014).
3. Shawcross, D. L., Davies, N. A., Williams, R., Jalan, R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. Journal of hepatology 40, 247-254 (2004).
4. Romero-Gomez, M., Jover, M., Galan, J. J., Ruiz, A. Gut ammonia production and its modulation. Metabolic brain disease 24, 147-157, doi: 10.1007/s11011-008-9124-3 (2009).
5. Zhang, X. D., Zhang, L. J., Wu, S. Y., Lu, G. M. Multimodality magnetic resonance imaging in hepatic encephalopathy: an update. World J Gastroenterol 20, 11262-11272, doi: 10.3748/wjg.v20.i32.11262 (2014).
6. Kale, R. A. et al. Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 43, 698-706, doi: 10.1002/hep.21114 (2006).
7. McPhail, M. J. et al. Modulation of neural activation following treatment of hepatic encephalopathy. Neurology 80, 1041-1047, doi: 10.1212/WNL.0b013e31828726e1 (2013).
8. Ahluwalia, V. et al. Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the gut-liver-brain axis. Metabolic brain disease 29, 1017-1025, doi: 10.1007/s11011-014-9507-6 (2014).
9. Rai, R. et al. Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy. Clin Transl Gastroenterol 6, e111, doi: 10.1038/ctg.2015.38 (2015).
10. Bajaj, J. S. et al. Linkage of gut microbiome with cognition in hepatic encephalopathy. American journal of physiology. Gastrointestinal and liver physiology 302, G168-175, doi: 10.1152/ajpgi.00190.2011 (2012).
11. Zhang, Z. et al. Large-scale survey of gut microbiota associated with MHE Via 16S rRNA-based pyrosequencing. The American journal of gastroenterology 108, 1601-1611, doi: 10.1038/ajg.2013.221 (2013).
12. Allampati, S. et al. Diagnosis of Minimal Hepatic Encephalopathy Using Stroop EncephalApp: A Multicenter US-Based, Norm-Based Study. The American journal of gastroenterology 111, 78-86, doi: 10.1038/ajg.2015.377 (2016).
13. Butterworth, R. F. Hepatic encephalopathy: a central neuroinflammatory disorder? Hepatology 53, 1372-1376, doi: 10.1002/hep.24228 (2011).
14. Bosoi, C. R., Tremblay, M., Rose, C. F. Induction of systemic oxidative stress leads to brain oedema in portacaval shunted rats. Liver international : official journal of the International Association for the Study of the Liver 34, 1322-1329, doi: 10.1111/liv.12414 (2014).
15. Shawcross, D. L. Is it time to target gut dysbiosis and immune dysfunction in the therapy of hepatic encephalopathy? Expert review of gastroenterology & hepatology 9, 539-542, doi: 10.1586/17474124.2015.1035257 (2015).
16. Chen, Y. et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54, 562-572 (2011).
17. Kakiyama, G. et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. Journal of hepatology 58, 949-955 (2013).
18. Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179-185, doi: 10.1038/nature10809 (2012).
19. Nakajima, M. et al. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver. Plos one 10, e0134234, doi: 10.1371/journal.pone.0134234 (2015).
20. Riggio, O. et al. Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients. Journal of clinical gastroenterology 12, 433-436 (1990).
21. Fouts, D. E., Torralba, M., Nelson, K. E., Brenner, D. A., Schnabl, B. Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease. Journal of hepatology 56, 1283-1292, doi: 10.1016/j.jhep.2012.01.019 (2012).
22. Bajaj, J. S. et al. A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy. Metabolic brain disease 27, 205-215, doi: 10.1007/s11011-012-9303-0 (2012).
23. Bosoi, C. R. et al. Increased brain lactate is central to the development of brain edema in rats with chronic liver disease. Journal of hepatology 60, 554-560, doi: 10.1016/j.jhep.2013.10.011 (2014).
24. Schuppan, D., Afdhal, N. H. Liver cirrhosis. Lancet 371, 838-851, doi: 10.1016/S0140-6736(08)60383-9 (2008).
25. Bajaj, J. S., Wade, J. B., Sanyal, A. J. Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology 50, 2014-2021, doi: 10.1002/hep.23216 (2009).
26. Malinchoc, M. et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31, 864-871, doi: 10.1053/he.2000.5852 (2000).
27. Bajaj, J. S. et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. American journal of physiology. Gastrointestinal and liver physiology 303, G675-685, doi: 10.1152/ajpgi.00152.2012 (2012).
28. Bajaj, J. S. et al. Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus. Scientific reports 5, 18559, doi: 10.1038/srep18559 (2015).
29. Gillevet, P., Sikaroodi, M., Keshavarzian, A., Mutlu, E. A. Quantitative assessment of the human gut microbiome using multitag pyrosequencing. Chem Biodivers 7, 1065-1075 (2010).
30. Segata, N. et al. Metagenomic biomarker discovery and explanation. Genome Biol 12, R60, doi: 10.1186/gb-2011-12-6-r60 (2011).
31. White, J. R., Nagarajan, N., Pop, M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. Plos Comput Biol 5, e1000352 (2009).
32. Langille, M. G. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31, 814-821, doi: 10.1038/nbt.2676 (2013).
33. Ahluwalia, V. et al. Correction of Hyponatremia Improves Cognition, Quality of Life, and Brain Edema in Cirrhosis. Journal of hepatology, doi: 10.1016/j.jhep.2014.07.033 (2014).
34. Ahluwalia, V. et al. Rifaximin Improves Brain Edema and Working Memory in Minimal Hepatic Encephalopathy: A Prospective fMRI Study. Hepatology 56, 162A (2012).
35. Provencher, S. W. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30, 672-679 (1993).
36. Provencher, S. W. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14, 260-264, doi: 10.1002/nbm.698 (2001).
37. Sarma, M. K. et al. Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy. Metabolic brain disease 26, 173-184, doi: 10.1007/s11011-011-9250-1 (2011).
38. Jenkinson, M., Bannister, P., Brady, M., Smith, S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage 17, 825-841 (2002).
39. Smith, S. M. Fast robust automated brain extraction. Human brain mapping 17, 143-155, doi: 10.1002/hbm.10062 (2002).
40. Woolrich, M. W., Ripley, B. D., Brady, M., Smith, S. M. Temporal autocorrelation in univariate linear modeling of FMRI data. NeuroImage 14, 1370-1386 (2001).
41. Westin, C. F. et al. Processing and visualization for diffusion tensor MRI. Med Image Anal 6, 93-108, doi: S1361841502000531 (2002).
42. Wakana, S. et al. Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage 36, 630-644, doi: S1053-8119(07)00138-3 (2007).
43. Hua, K. et al. Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification. Neuroimage 39, 336-347, doi: S1053-8119(07)00688-X(2008).
44. Naqvi, A., Rangwala, H., Keshavarzian, A., Gillevet, P. Network-based modeling of the human gut microbiome. Chem Biodivers 7, 1040-1050 (2010).
45. Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13, 2498-2504 (2003).