Fecal microbiota transplantation in alcohol related liver diseases
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The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.
Abstract
The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.
참고문헌 (41)
- Gao B, "Alcoholic liver disease : pathogenesis and new therapeutic targets", Gastroenterology, 141, pp.1572~1585 (2011)
- Shasthry SM, "New treatment options for alcoholic hepatitis", World J Gastroenterol, 22, pp.3892~3906 (2016)
- Mathurin P, "Early liver transplantation for severe alcoholic hepatitis", N Engl J Med, 365, pp.1790~1800 (2011)
- Lucey MR, "Alcoholic hepatitis", N Engl J Med, 360, pp.2758~2769 (2009)
- Anne-Marie Cassard, "Microbiota, a key player in alcoholic liver disease", Clinical and Molecular Hepatology, 24(2), pp.100~107 (2018), 대한간학회
- Gillevet P, "Quantitative assessment of the human gut microbiome using multitag pyrosequencing", Chem Biodivers, 7, pp.1065~1075 (2010)
- Lozupone CA, "Diversity, stability and resilience of the human gut microbiota", Nature, 489, pp.220~230 (2012)
- Qin J, "A metagenome-wide association study of gut microbiota in type 2 diabetes", Nature, 490, pp.55~60 (2012)
- Sender R, "Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans", Cell, 164, pp.337~340 (2016)
- Hartmann P, "Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice", Hepatology, 58, pp.108~119 (2013)
- Parlesak A, "Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease", J Hepatol, 32, pp.742~747 (2000)
- Sarin SK, "Microbiome as a therapeutic target in alcohol-related liver disease", J Hepatol, 70, pp.260~272 (2019)
- Bull-Otterson L, "Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment", PLoS One, 8, pp.e53028~ (2013)
- Leclercq S, "Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity", Proc Natl Acad Sci U S A, 111, pp.E4485~E4493 (2014)
- Chen Y, "Characterization of fecal microbial communities in patients with liver cirrhosis", Hepatology, 54, pp.562~572 (2011)
- Bajaj JS, "Continued alcohol misuse in human cirrhosis is associated with an impaired gut-liver axis", Alcohol Clin Exp Res, 41, pp.1857~1865 (2017)
- Lang S, "Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis", Hepatology, 71, pp.522~538 (2020)
- Casafont Morencos F, "Small bowel bacterial overgrowth in patients with alcoholic cirrhosis", Dig Dis Sci, 41, pp.552~556 (1996)
- Llopis M, "Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease", Gut, 65, pp.830~839 (2016)
- Forsyth CB, "Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis", Alcohol, 43, pp.163~172 (2009)
- Chang B, "The protective effect of VSL#3 on intestinal permeability in a rat model of alcoholic intestinal injury", BMC Gastroenterol, 13, pp.151~ (2013)
- Yan AW, "Enteric dysbiosis associated with a mouse model of alcoholic liver disease", Hepatology, 53, pp.96~105 (2011)
- Ferrere G, "Fecal microbiota manipulation prevents dysbiosis and alcoholinduced liver injury in mice", J Hepatol, 66, pp.806~815 (2017)
- Gao B, "MAIT cells: a novel therapeutic target for alcoholic liver disease?", Gut, 67, pp.784~786 (2018)
- DePeters EJ, "Rumen transfaunation", Immunol Lett, 162(2 Pt A), pp.69~76 (2014)
- Qin J, "A human gut microbial gene catalogue established by metagenomic sequencing", Nature, 464, pp.59~65 (2010)
- Zhang F, "Should we standardize the 1,700-year-old fecal microbiota transplantation?", Am J Gastroenterol, 107, pp.1755~ (2012)
- "Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat clostridium difficile infection not responsive to standard therapies"[URL]
- Tang G, "Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection : a metaanalysis?", Diagn Microbiol Infect Dis, 88, pp.322~329 (2017)
- Cui B, "Fecal microbiota transplantation through mid-gut for refractory Crohn’s disease : safety, feasibility, and efficacy trial results", J Gastroenterol Hepatol, 30, pp.51~58 (2015)
- Cui B, "Step-up fecal microbiota transplantation strategy : a pilot study for steroid-dependent ulcerative colitis", J Transl Med, 13, pp.298~ (2015)
- Zhang T, "Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease", Oncotarget, 8, pp.88894~88903 (2017)
- He Z, "Fecal microbiota transplantation cured epilepsy in a case with Crohn’s disease : the first report", World J Gastroenterol, 23, pp.3565~3568 (2017)
- Uygun A, "Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis", Medicine(Baltimore), 96, pp.e6479~ (2017)
- Philips CA, "Healthy donor fecal microbiota transplantation in steroidineligible severe alcoholic hepatitis : a pilot study", Clin Gastroenterol Hepatol, 15, pp.600~602 (2017)
- He Z, "Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn’s disease complicated with inflammatory mass", Sci Rep, 7, pp.4753~ (2017)
- Kirpich IA, "Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury : a pilot study", Alcohol, 42, pp.675~682 (2008)
- Stadlbauer V, "Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis", J Hepatol, 48, pp.945~951 (2008)
- Han SH, "Effects of probiotics(cultured Lactobacillus subtilis", Streptococcus faecium)in the treatment of alcoholic hepatitis : randomized-controlled multicenter study, 2015, pp.27, 1300~1306
- Philips CA, "Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis", Indian J Gastroenterol, 37, pp.215~225 (2018)
- Thursz MR, "Prednisolone or pentoxifylline for alcoholic hepatitis", N Engl J Med, 372, pp.1619~1628 (2015)