Probiotics Prevent Hepatic Encephalopathy in Patients With Cirrhosis: A Randomized Controlled Trial

Lunia, Manish Kumar; Sharma, Barjesh Chander; Sharma, Praveen; Sachdeva, Sanjeev; Srivastava, Siddharth

doi:10.1016/j.cgh.2013.11.006

Cited by 180 publications

(159 citation statements)

References 26 publications

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“…Previously, using a model of experimentally induced liver inflammation, we identified periph-eral TNF-␣-induced microglia activation and recruitment of monocytes to the brain as critical steps in the development of inflammation-associated sickness behaviors . Moreover, the clinical relevance of these findings is supported by the widely reported effect of anti-TNF-␣ therapies in improving sickness behaviors in patients suffering from a number of inflammatory diseases, often well before changes in tissue inflammation are observed (Lichtenstein et al, 2002;Strand et al, 2011;Weiler-Normann et al, 2013).…”

Section: Introductionsupporting

confidence: 51%

“…All procedures conformed to guidelines established by Canadian Council on Animal Care. For these experiments, we used the well characterized model of liver inflammation due to bile duct ligation (BDL) as described previously (Kerfoot et al, 2006;Nguyen et al, 2008;Nguyen et al, 2012;; sham ligated mice served as controls. This model is associated with elevated circulating cytokine levels (e.g., TNF-␣, IL-6) and the reproducible development of sickness behaviors .…”

Section: Methodsmentioning

confidence: 99%

“…Intravital microscopy of cerebral vasculature was conducted as described previously (Kerfoot et al, 2006;. Briefly, under ketamine (100 mg/kg)/ xylazine (10 mg/kg) anesthesia, a craniotomy was performed and the dura mater removed to expose the underlying pial vasculature.…”

Section: Methodsmentioning

confidence: 99%

“…spinning disk confocal microscope as described previously (Kerfoot et al, 2006). Mice were administered rhodamine-6G dye (to label circulating leukocytes) and CECs were labeled with an anti-CD31 antibody .…”

Section: Vsl#3 Treatment Reduces Leukocyte:cec Adhesive Interactions mentioning

confidence: 99%

“…VSL#3 also appears to be beneficial in some patients with advanced liver disease because VSL#3 ingestion decreased plasma levels of proinflammatory cytokines (e.g., TNF-␣) (Loguercio et al, 2005), improved QOL (Mittal et al, 2011), and reduced hospitalizations for hepatic encephalopathy (Dhiman et al, 2014). Furthermore, VSL#3 has recently been linked to an effect on brain function in that VSL#3 ingestion altered brain gene expression (Distrutti et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain

D’Mello

Ronaghan

Zaheer

et al. 2015

Journal of Neuroscience

153

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Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-␣ signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-tobrain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-␣ levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases.

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Section: Introductionsupporting

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Vsl#3 Treatment Reduces Leukocyte:cec Adhesive Interactions mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain

D’Mello

Ronaghan

Zaheer

et al. 2015

Journal of Neuroscience

153

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Probiotics for people with hepatic encephalopathy

Dalal

McGee

Riordan

et al. 2017

Cochrane Database of Systematic Reviews

103

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Background Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live microorganisms , which when administered in adequate amounts, may confer a health benefit on the host. Objectives To determine the beneficial and harmful e ects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. Selection criteria We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-e ects model metaanalysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean di erence (MD) with 95% confidence intervals (CI). Main results We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias.

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Hepatic Encephalopathy: Classification, Diagnosis, and Treatment

Dhiman

Rathi

2019

Evidence‐based Gastroenterology and Hepatology 4e

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Probiotics Prevent Hepatic Encephalopathy in Patients With Cirrhosis: A Randomized Controlled Trial

Cited by 180 publications

References 26 publications

Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain

Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain

Probiotics for people with hepatic encephalopathy

Hepatic Encephalopathy: Classification, Diagnosis, and Treatment

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