title: Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis.
abstract: Cognitive difficulties manifested by the growing elderly population with cirrhosis could be amnestic (memory-related) or non-amnestic (memory-unrelated). The underlying neuro-biological and gut-brain changes are unclear in this population. We aimed to define gut-brain axis alterations in elderly cirrhotics compared to non-cirrhotic individuals based on presence of cirrhosis and on neuropsychological performance. Age-matched outpatients with/without cirrhosis underwent cognitive testing (amnestic/non-amnestic domains), quality of life (HRQOL), multi-modal MRI (fMRI go/no-go task, volumetry and MR spectroscopy), blood (inflammatory cytokines) and stool collection (for microbiota). Groups were studied based on cirrhosis/not and also based on neuropsychological performance (amnestic-type, amnestic/non-amnestic-type and unimpaired). Cirrhotics were impaired on non-amnestic and selected amnestic tests, HRQOL and systemic inflammation compared to non-cirrhotics. Cirrhotics demonstrated significant changes on MR spectroscopy but not on fMRI or volumetry. Correlation networks showed that Lactobacillales members were positively while Enterobacteriaceae and Porphyromonadaceae were negatively linked with cognition. Using the neuropsychological classification amnestic/non-amnestic-type individuals were majority cirrhosis and had worse HRQOL, higher inflammation and decreased autochthonous taxa relative abundance compared to the rest. This classification also predicted fMRI, MR spectroscopy and volumetry changes between groups. We conclude that gut-brain axis alterations may be associated with the type of neurobehavioral decline or inflamm-aging in elderly cirrhotic subjects.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Vishwadeep
authors.initials: V
authors.lastname: Ahluwalia
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Steinberg
authors.affiliation: Division of Geriatrics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hobgood
authors.affiliation: Division of Geriatrics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Boling
authors.affiliation: Division of Geriatrics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Godschalk
authors.affiliation: Division of Geriatrics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Saima
authors.initials: S
authors.lastname: Habib
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: White
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fagan
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Gavis
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Ganapathy
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Stewart
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
authors.forename: Raffi
authors.initials: R
authors.lastname: Keradman
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Liu
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gillevet
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sikaroodi
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: F Gerard
authors.initials: FG
authors.lastname: Moeller
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001931:Brain Mapping; D003071:Cognition; D016207:Cytokines / Q000378:metabolism; D003710:Demography; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008103:Liver Cirrhosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D055442:Metabolome; D009483:Neuropsychological Tests; D011788:Quality of Life
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators