Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis.

Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging. 

https://digital.csic.es/bitstream/10261/306057/1/Acceso_restringido.pdf

Hepatic encephalopathy.

Microbiome therapeutics for hepatic encephalopathy

Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut-brain axis and its potential role as a therapeutic target in HE.

/pdf/the-role-of-intestinal-bacteria-and-gut-brain-axis-in-d609y3zbmj.pdf

The Role of Intestinal Bacteria and Gut-Brain Axis in Hepatic Encephalopathy.

Gut microbiota undergoes profound alterations in alcohol cirrhosis. Microbiota-derived products, e.g., short chain fatty acids (SCFA), regulate the homeostasis of the gut-liver axis. The objective was to evaluate the composition and functions of the intestinal microbiota in patients with alcohol-decompensated cirrhosis. Fecal samples of 18 patients and 18 healthy controls (HC) were obtained. Microbial composition was characterized by 16S rRNA amplicon sequencing, SCFA quantification was performed by gas chromatography (GC), and metagenomic predictive profiles were analyzed by PICRUSt2. Gut microbiota in the cirrhosis group revealed a significant increase in the pathogenic/pathobionts genera Escherichia/Shigella and Prevotella, a decrease in beneficial bacteria, such as Blautia, Faecalibacterium, and a decreased α-diversity (p < 0.001) compared to HC. Fecal SCFA concentrations were significantly reduced in the cirrhosis group (p < 0.001). PICRUSt2 analysis indicated a decrease in acetyl-CoA fermentation to butyrate, as well as an increase in pathways related to antibiotics resistance, and aromatic amino acid biosynthesis. These metabolic pathways have been poorly described in the progression of alcohol-related decompensated cirrhosis. The gut microbiota of these patients possesses a pathogenic/inflammatory environment; therefore, future strategies to balance intestinal dysbiosis should be implemented. These findings are described for the first time in the population of western Mexico.

/pdf/escherichia-shigella-scfas-and-metabolic-pathways-the-triad-3r4k2fil.pdf

Escherichia/Shigella, SCFAs, and Metabolic Pathways—The Triad That Orchestrates Intestinal Dysbiosis in Patients with Decompensated Alcoholic Cirrhosis from Western Mexico

OBJECTIVE Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota. METHODS This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders. RESULTS A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. CONCLUSIONS Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342).

Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial

Abstract Background Lower back pain and stiffness are the typical symptoms of ankylosing spondylitis (AS). In this study, muscle mass was assessed by muscle density, mechanical elasticity, and area. We investigated the characteristics of lumbar paraspinal-muscle (PSM) mass using muscle ultrasound shear-wave elastography (SWE), as well as the validity of this method for identifying patients with AS. Methods We recruited a representative cohort of 30 AS patients, and 27 healthy volunteers who were age- and sex-matched to the patient study group, investigated the Young’s modulus (YM), cross-sectional area (CSA) and thickness of lumbar multifidus (LM) muscle using SWE. This study did not need to be randomized. Data were collected at the department of ultrasonography of Guangdong Provincial Hospital of Chinese Medicine. We analyzed the data using SPSS version 18.0 (IBM Corp, Armonk, NY, USA). Normal distribution was evaluated by the Shapiro–Wilk test and Q–Q plots. Demographic and baseline data will be analyzed with standard descriptive statistics. Data will be presented as the mean ± standard deviation (SD). Non-normally distributed data are presented as medians with interquartile ranges (IQR). Results Young’s modulus (YM) of SWE in AS patients was significantly higher than that in volunteers. Percentage change in lumbar multifidus (LM) muscle cross-sectional area (CSA) and thickness were significantly lower in AS patients than in healthy volunteers on the left side of the body. Correlation analysis showed a positive correlation between percentage change in CSA and thickness in both volunteers and AS patients. In AS patients, YM was negatively correlated with percentage change of CSA and thickness on the right side, while increased disease duration in AS was associated with increased YM on the left. Conclusion AS patients showed reductions in LM muscle mass and function as the disease progressed, SWE could reflect these changes well. Trial registration. Chinese Clinical Trial Registry, ChiCTR2000031476. Registered 02/04/2020. http://www.chictr.org.cn/index.aspx . 

/pdf/mapping-of-lumbar-multifidus-stiffness-quantification-in-3jeifkwg.pdf

Mapping of lumbar multifidus stiffness Quantification in ankylosing spondylitis with shear-wave elastography

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Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial

Mapping of lumbar multifidus stiffness Quantification in ankylosing spondylitis with shear-wave elastography