Jasmohan S Bajaj1, Andrew Fagan1, Melanie B White1, James B Wade2, Phillip B Hylemon3,4, Douglas M Heuman1, Michael Fuchs1, Binu V John1, Chathur Acharya1, Masoumeh Sikaroodi2, Patrick M Gillevet2. 1. Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia. 2. Division of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia. 3. Division of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia. 4. Microbiome Analysis Center, George Mason University, Manassas, Virginia.
Abstract
OBJECTIVES: Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE. METHODS: Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis. RESULTS: Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One hundred twelve patients also provided saliva samples. Depending on the modality, 59%-82% of patients had MHE. Intertest Kappa for MHE was 0.15-0.35. Stool and salivary microbiota profiles with MHE were different from those without MHE. Individual microbiota signatures were associated with MHE in specific modalities. However, the relative abundance of Lactobacillaceae in the stool and saliva samples was higher in MHE, regardless of the modality used, whereas autochthonous Lachnospiraceae were higher in those without MHE, especially on PHES. On logistic regression, stool and salivary Lachnospiraceae genera (Ruminococcus and Clostridium XIVb) were associated with good cognition independent of clinical variables. DISCUSSION: Specific stool and salivary microbial signatures exist for individual cognitive testing strategies in MHE. The presence of specific taxa associated with good cognitive function regardless of modality could potentially be used to circumvent MHE testing.
OBJECTIVES: Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE. METHODS: Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis. RESULTS: Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One hundred twelve patients also provided saliva samples. Depending on the modality, 59%-82% of patients had MHE. Intertest Kappa for MHE was 0.15-0.35. Stool and salivary microbiota profiles with MHE were different from those without MHE. Individual microbiota signatures were associated with MHE in specific modalities. However, the relative abundance of Lactobacillaceae in the stool and saliva samples was higher in MHE, regardless of the modality used, whereas autochthonous Lachnospiraceae were higher in those without MHE, especially on PHES. On logistic regression, stool and salivary Lachnospiraceae genera (Ruminococcus and Clostridium XIVb) were associated with good cognition independent of clinical variables. DISCUSSION: Specific stool and salivary microbial signatures exist for individual cognitive testing strategies in MHE. The presence of specific taxa associated with good cognitive function regardless of modality could potentially be used to circumvent MHE testing.
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