Ameliorative Effect of Chitosan Oligosaccharides on Hepatic Encephalopathy by Reshaping Gut Microbiota and Gut-Liver Axis.

This study investigated the influence of chitosan oligosaccharides (COSs) on a thioacetamide-induced hepatic encephalopathy (HE) Wistar rat model. COS treatment statistically reduced the false neurotransmitters and blood ammonia in HE rats, along with the suppression of oxidative stress and inflammation. The disbalanced gut microbiota was detected in HE rats by 16S rDNA sequencing, but the abundance alterations of some intestinal bacteria at either the phylum or genus level were at least partly restored by COS treatment. According to metabolomics analysis of rat feces, six metabolism pathways with the greatest response to HE were screened, several of which were remarkably reversed by COS. The altered metabolites might serve as a bridge for the alleviated HE rats treated with COS and the enhanced intestinal bacterial structure. This study provides novel guidance to develop novel food or dietary supplements to improve HE diseases due to the potential beneficial effect of COS on gut-liver axis.

Dietary management of hepatic encephalopathy revisited.

PURPOSE OF REVIEW: The burden of hepatic encephalopathy on health services is increasing, and some degree of consensus in relation to drug therapy and prophylaxis has been reached. This review focuses on the role of nutritional interventions in the management of hepatic encephalopathy. RECENT FINDINGS: A number of relatively new pieces of evidence are emerging in relation to nutrition and hepatic encephalopathy as follows: first, reduction of protein intake is not useful for hepatic encephalopathy, but protein selection should be considered; second, oral supplementation with branched chain amino acids has a role not only for its nutritional effect in cirrhosis per se, but also for its effect in reducing the risk of recurrence of hepatic encephalopathy; third, alterations in gut microbiota develop in parallel with decompensation of cirrhosis, and modulation of gut microbiota may be effective for treating and preventing hepatic encephalopathy; fourth, prebiotics and probiotics are potentially useful in this aim, thus further research or trials on prebiotics and probiotics are required; fifth, micronutrient deficiency, which is common in end-stage liver disease, has adverse effects on the brain and may either directly cause encephalopathy per se, or interact with the mechanisms leading to hepatic encephalopathy. SUMMARY: Properly performed nutritional interventions are likely to be useful for patients with hepatic encephalopathy, but well conducted clinical trials are required. VIDEO ABSTRACT: http://links.lww.com/COCN/A7.

The gut microbiota and the liver: implications for clinical practice.

While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.

Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is characterised by subtle neurocognitive deficits without overt clinical manifestations. Although several trials have individually evaluated the role of prebiotics, probiotics and synbiotics, there is yet no consensus on the management of MHE. AIM: To estimate the efficacy of prebiotics, probiotics and synbiotics in MHE in randomised controlled trials. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Pooled relative risk and heterogeneity were estimated as the measures of association. RESULTS: Nine studies met our inclusion criteria. Use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32-0.50; P<0.001). Upon subgroup analysis, five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24-0.47; P<0.0001) with no inter-trial heterogeneity. In two trials each of probiotics and synbiotics, their use was associated with significant beneficial effects (RR 0.41, 95% CI 0.26-0.65; P<0.0001 and RR of 0.51, 95% CI 0.32-0.80; P=0.004 respectively). There were no major adverse events though probiotics and synbiotics were better tolerated than lactulose. CONCLUSIONS: The use of prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy. Among individual agents, lactulose appears to have the most beneficial effect, followed closely by probiotics and synbiotics.

[Vegetable protein diets with or without non-absorbable antibiotics for the treatment of chronic portal systemic encephalopathy]. / Son necesarios los antibioticos inabsorbibles en pacientes con encefalopatía hepática manejados con dieta de proteínas vegetales?

Five patients with mild chronic portal systemic encephalopathy (PSE) were studied. The study was designed in a double cross over fashion in which each patient received during period I a 40 g vegetable protein diet as single treatment. During period II three g/day of oral kanamycin were added and then new periods of single vegetable protein diet (period III) and vegetable protein diet plus kanamycin (period IV) were introduced (identical to periods I and II respectively). Each period lasted two weeks. Several biweekly assessements-tests were determined including: mental state, asterixis grade, electroencephalograms, number connection tests, figure connection tests, blood ammonia levels and stool counts of total aerobes/anaerobes per g/feces were done. During the study none of the patients developed acute encephalopathy. In any case it was detected a significant improvement of the PSE parameters assessed with the addition of oral kanamycin. Fecal counts were very similar during the various periods of the study. We conclude that in mild portal systemic encephalopathy controlled with vegetable protein diet, the addition of non absorbable antibiotics is not mandatory for the management of these patients and may represent a potential risk of serious side effects. At the beginning of treatment vegetable protein diet should be administered and only in case of failure, antibiotics are to be indicated.