The role of microbiota in hepatic encephalopathy

Bajaj, Jasmohan S.

doi:10.4161/gmic.28684

Cited by 149 publications

(121 citation statements)

References 41 publications

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“…Changes in bacterial composition characterised by a relative decrease in potentially beneficial autochthonous taxa as well as a relative overgrowth of potentially pathogenic taxa (such as Staphylococcaeae, Enterobacteriaceae, and Enterococcaceae) was independently associated with severity of liver disease and the development of endotoxemia and HE, suggesting a direct pathogenic role (Bajaj 2014;Bajaj et al 2012aBajaj et al , 2014bChen et al 2011;Nava and Stappenbeck 2011). The pathophysiological mechanisms underpinning this are complex, and it has been suggested that the reduced production of SCFAs, anti-bacterial peptides and changes in bile acid production resulting from enteric dysbiosis all contribute to worsening disease severity.…”

Section: Metab Brain Dismentioning

confidence: 98%

Clinical science workshop: targeting the gut-liver-brain axis

et al. 2015

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A clinical science workshop was held at the ISHEN meeting in London on Friday 11th September 2014 with the aim of thrashing out how we might translate what we know about the central role of the gut-liver-brain axis into targets which we can use in the treatment of hepatic encephalopathy (HE). This review summarises the integral role that interorgan ammonia metabolism plays in the pathogenesis of HE with specific discussion of the roles that the small and large intestine, liver, brain, kidney and muscle assume in ammonia and glutamine metabolism. Most recently, the salivary and gut microbiome have been shown to underpin the pathophysiological changes which culminate in HE and patients with advanced cirrhosis present with enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across a leaky gut epithelial barrier. Resident macrophages within the liver are able to sense bacterial degradation products initiating a pro-inflammatory response within the hepatic parenchyma and release of cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-8 into the systemic circulation. The endotoxemia and systemic inflammatory response that are generated predispose both to the development of infection as well as the manifestation of covert and overt HE. Co-morbidities such as diabetes and insulin resistance, which commonly accompany cirrhosis, may promote slow gut transit, promote bacterial overgrowth and increase glutaminase activity and may need to be acknowledged in HE risk stratification assessments and therapeutic regimens. Therapies are discussed which target ammonia production, utilisation or excretion at an individual organ level, or which reduce systemic inflammation and endotoxemia which are known to exacerbate the cerebral effects of ammonia in HE. The ideal therapeutic strategy would be to use an agent that can reduce hyperammonemia and reduce systemic inflammation or perhaps to adopt a combination of therapies that can address both.

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Section: Metab Brain Dismentioning

confidence: 98%

Clinical science workshop: targeting the gut-liver-brain axis

et al. 2015

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“…Therapeutic strategies of neuroinflammatory response in HE are multiple (Butterworth 2011b), including nonabsorbable disaccharides (such as lactulose ), antibiotics (such as rifaximin (Kimer et al 2014;Vilstrup et al 2014)), probiotics or fecal transplantation (Bajaj 2014;Dhiman 2013;Floch 2014;Quigley and Monsour 2013). These treatments may help remove both ammonia and inflammatory cytokines.…”

Section: Perspectivesmentioning

confidence: 98%

PET and MR imaging of neuroinflammation in hepatic encephalopathy

Yang

et al. 2014

Metab Brain Dis

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Neurological or psychiatric abnormalities associated with hepatic encephalopathy (HE) range from subclinical findings to coma. HE is commonly accompanied with the accumulation of toxic substances in bloodstream. The toxicity effect of hyperammonemia on astrocyte, such as the alteration in neurotransmission, oxidative stress, astrocyte swelling, is considered as an important factor in the pathogenesis of HE. Besides, neuroinflammation has captured more attention in the process of HE, but the mechanism of neuroinflammation leading to HE remains unclear. Molecular imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting activated microglia and/ or other mediators appear to be promising noninvasive approaches to assess HE. This review focuses on novel imaging and therapy strategies of neuroinflammation in HE.

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“…A limited number of studies investigating the gut-liver-brain axis in cirrhosis have proposed that gut microbiome composition may impact on the neurocognitive function (Bajaj 2014;Rai et al 2015). By sequencing bacterial the 16S rDNA gene from the faeces of cirrhotic patients with and without minimal HE (MHE), Zhang and colleagues observed an abundance of Streptococcaceae and Veillonellaceae in cirrhotic patients vs normal individuals.…”

mentioning

confidence: 98%

What is new about diet in hepatic encephalopathy

2015

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There is a relationship between hepatic encephalopathy (HE) protein malnutrition and muscle wasting. Muscle may play an alternative role in ammonia detoxification. Molecular mechanisms responsible for muscle depletion are under investigation. Specific nutrients may interact to reverse the molecular pathways involved in muscle wasting at an early stage. Training exercises have also been proposed to improve skeletal muscle mass. However, these data refer to small groups of patients. The amelioration of muscle mass may potentially help to prevent HE. The pathogenesis of HE is associated with modifications of the gut microbiota and diet is emerging to play a relevant role in the modulation of the gut milieu. Vegetarian and fibre-rich diets have been shown to induce beneficial changes on gut microbiota in healthy people, with reduction of Bacteroides spp., Enterobacteriaceae, and Clostridium cluster XIVa bacteria. By way of contrast, it has been suggested that a high-fat or protein diet may increase Firmicutes and reduce Bacteroidetes phylum. Milk-lysozyme and milk-oligosaccharides have also been proposed to induce a "healthy" microbiota. At present, no studies have been published describing the modification of the gut microbiota in cirrhotic patients with HE as a response to specific diets. New research is needed to evaluate the potentiality of foods in the modulation of gut microbiota in liver disease and HE.

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The role of microbiota in hepatic encephalopathy

Cited by 149 publications

References 41 publications

Clinical science workshop: targeting the gut-liver-brain axis

Clinical science workshop: targeting the gut-liver-brain axis

PET and MR imaging of neuroinflammation in hepatic encephalopathy

What is new about diet in hepatic encephalopathy

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