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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.

SUBMITTER: Bajaj JS

PROVIDER: S-EPMC5138827 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

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Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis.

Bajaj Jasmohan S JS Ahluwalia Vishwadeep V Steinberg Joel L JL Hobgood Sarah S Boling Peter A PA Godschalk Michael M Habib Saima S White Melanie B MB Fagan Andrew A Gavis Edith A EA Ganapathy Dinesh D Hylemon Phillip B PB Stewart Karen E KE Keradman Raffi R Liu Eric J EJ Wang Jessica J Gillevet Patrick M PM Sikaroodi Masoumeh M Moeller F Gerard FG Wade James B JB

Scientific reports 20161206

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 ...[more]

PMID: 27922089

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Project description:Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child-Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child-Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(>F) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child-Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI (r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway "bacterial invasion of epithelial cells" in patients, was highly negatively correlated with SBT (r = -0.57, p < 0.01). The severity of microbiota dysbiosis in LC patients depends on SBT rather than Child-Pugh score. SBT per se might be significantly related to the gut microbiota abnormalities observed in patients with LC.

Project description:Dysbiosis of gut microbiota and metabolome is a frequently encountered condition in liver cirrhosis (LC) patients. The severity of liver dysfunction was found to be correlated with the degree of microbial dysbiosis. Several clinical studies have indicated liver function improvement after therapeutic splenectomy for LC-induced hypersplenism. We sought to determine whether such post-splenectomy outcome is pertinent to modulation of the abnormal gut microenvironment in LC patients. A cross-sectional study including 12 LC patients and 16 healthy volunteers was first conducted, then a before-after study in the cohort of patients was carried out before and 6 months after splenectomy. Fecal samples were collected in hospital. Temporal bacterial (n = 40) and metabolomics (n = 30) profiling was performed using 16s rRNA gene sequencing and ultra performance liquid chromatography/mass spectrometer (UPLC/MS), respectively. Our results revealed that microbial composition in patients was clearly different from that in healthy controls (HCs), evidenced by considerable taxonomic variation. Along with improved liver function (Child-Pugh score), the patients also displayed similar gut microbiota profile and predicted metagenome function to that of HCs after splenectomy. Enterobacteriaceae and Streptococcaceae, two LC-enriched families showing positive relation with Child-Pugh score, exhibited significantly decreased abundance after splenectomy. At the genus level, 11 genera were differentially abundant between patients and HCs, but 9 genera of them restituted to normal levels by certain degree after splenectomy. PICRUSt analysis showed that the relative abundance of 17 KEGG pathways was partially restored after splenectomy. Four of them were amino acid-related pathways: lysine degradation, tryptophan degradation, amino acid metabolism, and protein digestion and absorption. These findings were supported by metabonomics results which showed that relative abundance of amino acid and corresponding catabolites changed toward normal. In addition to the variations in the relative abundances of bacteria and metabolites, the correlation between them also altered in patients after splenectomy. Dysbiosis in gut microbiome and related metabolism of LC patients was partially corrected after splenectomy. Whether the improved gut microenvironment could prevent LC-related complications and delay the progress of LC is a propitious objective for future study. TRIAL REGISTRATION:ChiCTR-OOB-15007409. Registered November 15, 2015.

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Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis.

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Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis.

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