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Linkage of gut microbiome with cognition in hepatic encephalopathy
Open accessAbstract
Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE (n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae, Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae) compared with controls. We found altered flora (higher Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.
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“the bacterial family Porphyromonadaceae has been linked to declines in cognition and affective disorders”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Bajaj et al., 2012
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“In individuals with alcohol addiction, drinking can disrupt intestinal barrier function, also known as intestinal leakage [11, 12].”
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Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888
Nucleic acid techniques in bacterial systematics
Stackebrandt, E. S., & Goodfellow, M. (1991) · Wiley eBooks · Cited by 9,460
Lane, D. (1991) · Medical Entomology and Zoology · Cited by 8,190
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228
Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples
White, J. R., Nagarajan, N., & Pop, M. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000352 · Cited by 1,599
Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives
Joossens, M., Huys, G., Cnockaert, M., De Preter, V., Verbeke, K., Rutgeerts, P., Vandamme, P., & Vermeire, S. (2011) · Gut · doi:10.1136/gut.2010.223263 · Cited by 1,063
Characterization of fecal microbial communities in patients with liver cirrhosis
Chen, Y., Yang, F., Lu, H., Wang, B., Chen, Y., Lei, D., Wang, Y., Zhu, B., & Li, L. (2011) · Hepatology · doi:10.1002/hep.24423 · Cited by 1,038
Microbial community profiling for human microbiome projects: Tools, techniques, and challengesPreprint
Hamady, M., & Knight, R. D. (2009) · Genome Research · doi:10.1101/gr.085464.108 · Cited by 1,031
The microbiome-gut-brain axis: from bowel to behavior
Cryan, J. F., & O’Mahony, S. M. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01664.x · Cited by 990
Neuropsychological characterization of hepatic encephalopathy
Weißenborn, K., Ennen, J. C., Schomerus, H., Rückert, N., & Hecker, H. (2001) · Journal of Hepatology · doi:10.1016/s0168-8278(01)00026-5 · Cited by 796
Liu, Q., Duan, Z. P., Ha, D. K., Bengmark, S., Kurtovic, J., & Riordan, S. M. (2004) · Hepatology · doi:10.1002/hep.20194 · Cited by 636
Bacterial Infections, Sepsis, and Multiorgan Failure in Cirrhosis
Tandon, P., & García–Tsao, G. (2008) · Seminars in Liver Disease · doi:10.1055/s-2008-1040319 · Cited by 549
Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells
Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J., & Powrie, F. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.010 · Cited by 528
Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club
Wong, F. S.-H., Bernardi, M., Balk, R., Christman, B., Moreau, R., Garcia-Tsao, G., Patch, D., Soriano, G., Hoefs, J., & Navasa, M. (2005) · Gut · doi:10.1136/gut.2004.038679 · Cited by 390
Pathogenetic mechanisms of hepatic encephalopathy
Häussinger, D., & Schliess, F. (2008) · Gut · doi:10.1136/gut.2007.122176 · Cited by 390
Leaky Gut in Alcoholic Cirrhosis: A Possible Mechanism for Alcohol-Induced Liver Damage
Keshavarzian, A., HOLMES, E. W., Patel, M., Iber, F. L., Fields, J. Z., & Pethkar, S. (1999) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.00797.x · Cited by 381
Mutlu, E., Keshavarzian, A., Engen, P. A., Forsyth, C. B., Sikaroodi, M., & Gillevet, P. M. (2009) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.01022.x · Cited by 371
Self-citationKang, S., Denman, S. E., Morrison, M., Yu, Z., Dore, J. M., Leclerc, M., & McSweeney, C. S. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21319 · Cited by 365
Persistence of Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy
Bajaj, J. S., Schubert, C. M., Heuman, D. M., Wade, J. B., Gibson, D. P., Topaz, A., Saeian, K., Hafeezullah, M., Bell, D. E., Sterling, R. K., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.02.015 · Cited by 310
Self-citationHighlighting new phylogenetic specificities of Crohn's disease microbiota
Mondot, S., Kang, S., Furet, J., de Cárcer, D. A., McSweeney, C., Morrison, M., Marteau, P., Doré, J., & Leclerc, M. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21436 · Cited by 283
Jin, J.-J., Kim, H.-D., Maxwell, J. A., Li, L., & Fukuchi, K. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-23 · Cited by 279
Shawcross, D. L., Sharifi, Y., Canavan, J. B., Yeoman, A. D., Abeles, R. D., Taylor, N. J., Auzinger, G. M., Bernal, W. E., & Wendon, J. A. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.07.045 · Cited by 277
Role of ammonia and inflammation in minimal hepatic encephalopathy
Shawcross, D. L., Wright, G. A. K., Damink, S. W. M. O., & Jalan, R. (2007) · Metabolic Brain Disease · doi:10.1007/s11011-006-9042-1 · Cited by 265
Bajaj, J. S., Heuman, D. M., Wade, J. B., Gibson, D. P., Saeian, K., Wegelin, J. A., Hafeezullah, M., Bell, D. E., Sterling, R. K., Stravitz, R. T., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.08.061 · Cited by 245
Self-citationReview article: the modern management of hepatic encephalopathy
BAJAJ, J. S. (2010) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04211.x · Cited by 243
Self-citationObata, T., Goto, Y., Kunisawa, J., Sato, S., Sakamoto, M., Setoyama, H., Matsuki, T., Nonaka, K., Shibata, N., Gohda, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001061107 · Cited by 229
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Bajaj, J. S., Hafeezullah, M., Franco, J., Varma, R. R., Hoffmann, R. G., Knox, J. F., Hischke, D., Hammeke, T. A., Pinkerton, S. D., & Saeian, K. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.021 · Cited by 225
Self-citationBajaj, J. S., Zadvornova, Y., Heuman, D. M., Hafeezullah, M., Hoffmann, R. G., Sanyal, A. J., & Saeian, K. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.80 · Cited by 215
Self-citationNew assessment of hepatic encephalopathy
Córdoba, J. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.11.015 · Cited by 215
Zoetendal, E. G., Amor, K. B., Harmsen, H. J. M., Schut, F., Akkermans, A. D. L., & de Vos, W. M. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.9.4225-4232.2002 · Cited by 129
Dysbiosis in Pouchitis: Evidence of Unique Microfloral Patterns in Pouch Inflammation
Komanduri, S., Gillevet, P. M., Sikaroodi, M., Mutlu, E., & Keshavarzian, A. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.01.001 · Cited by 120
Self-citationVanhoutte, T., Preter, V. D., Brandt, E. D., Verbeke, K., Swings, J., & Huys, G. R. B. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.00233-06 · Cited by 116
Evidence of Persistent Cognitive Impairment After Resolution of Overt Hepatic Encephalopathy
Riggio, O., Ridola, L., Pasquale, C., Nardelli, S., Pentassuglio, I., Moscucci, F., & Merli, M. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2010.10.002 · Cited by 108
Effect of Lactitol and Lactulose Administration on the Fecal Flora in Cirrhotic Patients
Riggio, O., Varriale, M., Testore, G. P., Rosa, R. D., Rosa, E. D., Merli, M., Romiti, A., Candiani, C., & Capocaccia, L. (1990) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-199008000-00016 · Cited by 108
Quantitative Assessment of the Human Gut Microbiome Using Multitag Pyrosequencing
Gillevet, P. M., Sikaroodi, M., Keshavarzian, A., & Mutlu, E. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900322 · Cited by 105
Self-citationAmmonia and inflammation in the pathogenesis of hepatic encephalopathy
Wright, G. A. K., & Jalan, R. (2007) · Hepatology · doi:10.1002/hep.21843 · Cited by 69
Liver X receptors are negative regulators of cardiac hypertrophy via suppressing NF- B signalling
Wu, S., Yin, R., Ernest, R., Li, Y., Zhelyabovska, O., Luo, J., Yang, Y., & Yang, Q. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp180 · Cited by 68
Abnormal metabolism of secondary bile acids in patients with cirrhosis
Vlahcevic, Z. R., Buhac, I., Bell, C. C., & Swell, L. (1970) · Gut · doi:10.1136/gut.11.5.420 · Cited by 63
Network‐Based Modeling of the Human Gut Microbiome
Naqvi, A. S., Rangwala, H., Keshavarzian, A., & Gillevet, P. M. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900324 · Cited by 60
Self-citationRomero‐Gómez, M., Córdoba, J., Jover, R., del Olmo, J., Fernández-Palacín, A., Flavià, M., Compañy, L., Poveda, M. J., & Felipo, V. (2006) · Medicina Clínica · doi:10.1157/13091264 · Cited by 60
Targeting IL-23 in human diseases
D’Elios, M. M., Prete, G. D., & Amedei, A. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.497143 · Cited by 30
Evaluation of 24-hour gastric acidity in patients with hepatic cirrhosis
Savarino, V., Mela, G. S., Zentilin, P., Mansi, C., Mele, M. R., Vigneri, S., Cutela, P., Vassallo, A., Dallorto, E., & Celle, G. (1996) · Journal of Hepatology · doi:10.1016/s0168-8278(96)80067-5 · Cited by 25
Ridlon, J. M., McGarr, S. E., & Hylemon, P. B. (2005) · Clinica Chimica Acta · doi:10.1016/j.cccn.2005.02.004 · Cited by 14
Self-citationChecks and Balances: IL-23 in the Intestine
Huber, S., & Flavell, R. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.005 · Cited by 4
Immunomodulation: a new approach to the therapy of cirrhosis?
Marra, F., & Annunziato, F. (2010) · Gut · doi:10.1136/gut.2009.203109 · Cited by 3
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Metadata
- Authors
- Bajaj, J. S., Ridlon, J. M., Hylemon, P. B., Thacker, L. R., Heuman, D. M., Smith, S., Sikaroodi, M., & Gillevet, P. M.
- Affiliations
- Divisions of 1Gastroenterology, Hepatology and Nutrition,
- Virginia Commonwealth University (US)
- George Mason University (US)
- Corresponding author
- Bajaj, Jasmohan S.
- ORCID
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2012-01
- Volume
- 302
- Issue
- 1
- Pages
- G168-G175
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC3345956
- OpenAlex
- W2058029859
- Cited by
- 547
- References
- 49
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 43 · 2023: 60 · 2022: 40 · 2021: 45 · 2020: 42 · 2019: 49 · 2018: 43 · 2017: 36 · 2016: 34 · 2015: 32 · 2014: 33 · 2013: 25 · 2012: 23
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American College of Gastroenterology
- Virginia Commonwealth University
- National Institute on Alcohol Abuse and Alcoholism (R01AA020203)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087913)
- National Center for Complementary and Alternative Medicine
- National Center for Complementary and Integrative Health (U01AT004428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- hepatic encephalopathy, gut microbiota, cognitive impairment, liver cirrhosis, inflammation, endotoxemia, rifaximin, Veillonellaceae, Enterobacteriaceae, Alcaligenaceae, Porphyromonadaceae, inflammatory cytokines, intestinal barrier dysfunction, systems biology
- MeSH terms
- Rifaximin, Cognition Disorders, Endotoxins, Feces, Female, Gastrointestinal Agents, Hepatic Encephalopathy, Humans, Lactulose, Liver Cirrhosis, Male, Middle Aged, Rifamycins, Cytokines, Gastrointestinal Tract, Systems Biology, Metagenome
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