Rifaximin in non‐alcoholic steatohepatitis: An open‐label pilot study

Cobbold, Jeremy; Atkinson, Stephen R.; Marchesi, Julian R.; Smith, Ann; Wai, Sann N.; Stove, J; Shojaee‐Moradie, Fariba; Jackson, Nicola; Umpleby, A. Margot; Fitzpatrick, Julie; Thomas, E. Louise; Bell, Jimmy D.; Holmes, Elaine; Taylor-Robinson, Simon D; Goldin, Robert D.; Yee, Michael; Anstee, Quentin M.; Thursz, Mark

doi:10.1111/hepr.12904

Cited by 45 publications

(36 citation statements)

References 41 publications

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“…Several human studies of antibiotics in NAFLD have assessed the effect of rifaximin, a nonsystemic antibiotic (Table ) . Rifaximin is currently indicated in the United States to prevent overt hepatic encephalopathy recurrence and to treat travellers’ diarrhoea and irritable bowel syndrome (IBS) with diarrhoea .…”

Section: Treatments For Nafld That Target Gut Microbiotamentioning

confidence: 99%

Review article: emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications

Jayakumar

Loomba

2019

Aliment Pharmacol Ther

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Summary Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent disorder associated with obesity and diabetes. Few treatment options are effective for patients with NAFLD, but connections between the gut microbiome and NAFLD and NAFLD‐associated conditions suggest that modulation of the gut microbiota could be a novel therapeutic option. Aim To examine the effect of the gut microbiota on pathophysiologic causes of NAFLD and assess the potential of microbiota‐targeting therapies for NAFLD. Methods A PubMed search of the literature was performed; relevant articles were included. Results The composition of bacteria in the gastrointestinal tract can enhance fat deposition, modulate energy metabolism and alter inflammatory processes. Emerging evidence suggests a role for the gut microbiome in obesity and metabolic syndrome. NAFLD is often considered the hepatic manifestation of metabolic syndrome, and there has been tremendous progress in understanding the association of gut microbiome composition with NAFLD disease severity. We discuss the role of the gut microbiome in NAFLD pathophysiology and whether the microbiome composition can differentiate the two categories of NAFLD: nonalcoholic fatty liver (NAFL, the non‐progressive form) vs nonalcoholic steatohepatitis (NASH, the progressive form). The association between gut microbiome and fibrosis progression in NAFLD is also discussed. Finally, we review whether modulation of the gut microbiome plays a role in improving treatment outcomes for patients with NAFLD. Conclusions Multiple pathophysiologic pathways connect the gut microbiome with the pathophysiology of NAFLD. Therefore, therapeutics that effectively target the gut microbiome may be beneficial for the treatment of patients with NAFLD.

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Section: Treatments For Nafld That Target Gut Microbiotamentioning

confidence: 99%

Review article: emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications

Jayakumar

Loomba

2019

Aliment Pharmacol Ther

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“…Polymyxin B and neomycin reduce hepatic steatosis and endotoxin levels in animal models [ 106 , 107 ]. Studies on rifaximin, active on Gram-negative bacteria, show conflicting results in NASH patients ranging from a significant reduction of ALT, endotoxin and IL-10 levels [ 108 ] to the inefficacy on fat liver content and ALT levels [ 109 ]. Further studies on antibiotics as GLA-modulators are needed, especially to evaluate risks/benefits in light of recent data showing a possible increased risk of obesity due to antibiotic exposure in early life [ 104 , 110 ].…”

Section: Therapeutic Prospectivesmentioning

confidence: 99%

Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

2017

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Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

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“…If there was greater use of medical therapy for HE in the FMT arm compared to standard-of-care, this difference may be an alternative explanation for the apparent reduced HE burden in these patients. Furthermore, recommencement of rifaximin shortly after FMT would surely be inappropriate, as the broad-spectrum nature of this non-absorbable antibiotic 2,3 would intuitively minimise the chance of successful colonisation of recipients with bacterial communities present within the FMT.…”

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confidence: 99%