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.
“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
The Results (Table 6) and Discussion link Porphyromonadaceae to poor performance on cognitive tests in patients with cirrhosis, particularly those with hepatic encephalopathy. Our copy does not report an association between Porphyromonadaceae and affective disorders, so that part of the claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn individuals with alcohol addiction, drinking can disrupt intestinal barrier function, also known as intestinal leakage.
“In individuals with alcohol addiction, drinking can disrupt intestinal barrier function, also known as intestinal leakage [11, 12].”
From Research protocol of the efficacy of probiotics for the treatment of alcohol use disorder among adult males: A comparison with placebo and acceptance and commitment therapy in a randomized controlled trial (2023) · cites this paper as [12]
The Discussion reports endotoxemia and microbiome–inflammation associations in patients with hepatic encephalopathy, but does not say that drinking disrupts the intestinal barrier in people with alcohol addiction. Searches for alcohol-related intestinal permeability, barrier function, and leaky gut found only a related title in the References, not a statement of the claim in this paper. (LLM, conf=0.72)
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Self-citationCognitive decline, dietary factors and gut–brain interactions
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Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia
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Self-citationCrosstalk between the microbiota-gut-brain axis and depression
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Large-Scale Survey of Gut Microbiota Associated With MHE Via 16S rRNA-Based Pyrosequencing
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The role of microbiota in hepatic encephalopathy
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Self-citationColonic inflammation and secondary bile acids in alcoholic cirrhosis
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Self-citationImmune Dysfunction in Cirrhosis
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Gut microbiota and liver diseases
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Gut Microbiota: Its Role in Hepatic Encephalopathy
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Self-citationRole of the intestinal microbiome in liver disease
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Role of gut microbiota in liver disease
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- 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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