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Abstract Details
Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis
Gut Microbes. Jan-Dec 2021;13(1):1953247. doi: 10.1080/19490976.2021.1953247.
Jasmohan S Bajaj1, Amirhossein Shamsaddini2, Andrew Fagan1, Sara McGeorge1, Edith Gavis1, Masoumeh Sikaroodi2, Lisa A Brenner3, James B Wade4, Patrick M Gillevet2
Author information
1Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia, USA.
2Microbiome Analysis Center, George Mason University, Manassas, Virginia.
3Departments of Physical Medicine and Rehabilitation, Psychiatry, & Neurology, VA Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colorado, and University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
4Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Abstract
Most cirrhosis etiologies, such as alcohol, hepatitis C, and obesity, involve behavior that require the loss of inhibitory control. Once cirrhosis develops, patients can also develop cognitive impairment due to minimal hepatic encephalopathy (MHE). Both processes could have distinct imprints on the gut-liver-brain axis. Determine the impact of inhibitory control versus traditional cirrhosis-related cognitive performance on gut microbial composition and function. Outpatients with cirrhosis underwent two tests for MHE: inhibitory control test (MHEICT, computerized associated with response inhibition) and psychometric hepatic encephalopathy score (MHEPHES, paper-pencil HE-specific associated with subcortical impairment) along with stool collection for metagenomics. MHEICT/not, MHEPHES/not, and discordant (positive on one test but negative on the other) were analyzed for demographics, bacterial species, and gut-brain modules (GBM) using multi-variable analyses. Ninety-seven patients [47 (49%) MHEPHES, 76 (78%) MHEICT, 41 discordant] were enrolled. MHEPHES/not: Cirrhosis severity was worse in MHEPHES without differences in alpha/beta diversity on bacterial species or GBMs. Pathobionts (Enterobacteriaceae) and γ-amino-butryic acid (GABA) synthesis GBM were higher in MHEPHES. MHEICT/not: We found similar cirrhosis severity and metagenomic alpha/beta diversity in MHEICT versus not. However, alpha/beta diversity of GBMs were different in MHEICT versus No-MHE patients. Alistipes ihumii, Prevotella copri, and Eubacterium spp. were higher, while Enterococcus spp. were uniquely lower in MHEICT versus no-MHE and discordant comparisons. GBMs belonging to tryptophan, menaquinone, GABA, glutamate, and short-chain fatty acid synthesis were also unique to MHEICT. Gut microbial signature of impaired inhibitory control, which is associated with addictive disorders that can lead to cirrhosis, is distinct from cirrhosis-related cognitive impairment.