Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis

Banerjee, Pratik; Pierre, Joseph F.; Higgins, Daleniece; Dutta, Soma; Heda, Rajiv; Khan, Sobia; Mupparaju, Vamsee; Mas, Valeria R.; Nair, Satheesh; Eason, James D.; Kleiner, David E.; Maluf, Daniel G.

doi:10.1097/txd.0000000000001033

Cited by 18 publications

(20 citation statements)

References 55 publications

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“…A meta-analysis of four RCTs [141] found that the synergic use of prebiotics and probiotics significantly reduced the infection rates (7% vs. 35%) after LT; these results were later confirmed by a fifth RCT [137]. Moreover, gut dysbiosis was also associated with the development of non-anastomotic biliary strictures [142], hepatic generation after partial liver grafts [132], and the recurrence of liver disease [143].…”

Section: Faecalibacterium Lachnospiramentioning

confidence: 94%

Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases

Binda¹,

Gibiino²,

Coluccio³

et al. 2022

Microorganisms

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Recent evidence regarding microbiota is modifying the cornerstones on pathogenesis and the approaches to several gastrointestinal diseases, including biliary diseases. The burden of biliary diseases, indeed, is progressively increasing, considering that gallstone disease affects up to 20% of the European population. At the same time, neoplasms of the biliary system have an increasing incidence and poor prognosis. Framing the specific state of biliary eubiosis or dysbiosis is made difficult by the use of heterogeneous techniques and the sometimes unwarranted invasive sampling in healthy subjects. The influence of the microbial balance on the health status of the biliary tract could also account for some of the complications surrounding the post-liver-transplant phase. The aim of this extensive narrative review is to summarize the current evidence on this topic, to highlight gaps in the available evidence in order to guide further clinical research in these settings, and, eventually, to provide new tools to treat biliary lithiasis, biliopancreatic cancers, and even cholestatic disease.

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Section: Faecalibacterium Lachnospiramentioning

confidence: 94%

Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases

Binda¹,

Gibiino²,

Coluccio³

et al. 2022

Microorganisms

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“…Besides, there is a relative abundance of potential pathogens, such as Gram-negative Proteobacteria, Enterobacteriaceae, and Escherichia spp. among patients with NASH, when compared to healthy controls, while Faecalibacterium prausnitzii and Akkermansia muciniphila are relatively diminished [ 33 , 34 , 35 ]. Faecalibacterium prausnitzii , a Gram-positive anaerobe bacterium, Eubacterium rectale , Eubacterium halii , and Anaerostipes caccae are well-known short-chain fatty acids (SCFAs) producers, particularly butyrate.…”

Section: Nafld Gut Dysbiosis and Microbial Signaturesmentioning

confidence: 99%

“…Akkermansia muciniphila , a mucin-producing, Gram-negative anaerobe bacterium, when co-cultured with the butyrate-producing Faecalibacterium prausnitzii , Eubacterium rectale , Eubacterium halii , and Anaerostipes caccae results in an enhanced production of butyrate. Therefore, Akkermansia muciniphila , apart from its beneficial role in the gut epithelium per se, may promote the growth of other bacteria with anti-inflammatory properties [ 33 , 34 , 35 ]. Children with NAFLD and NASH have a decreased proportion of Oscillospira spp.…”

Section: Nafld Gut Dysbiosis and Microbial Signaturesmentioning

confidence: 99%

Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.

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“…Satapathy SK et al found loss of AKM in patients after LT, especially in patients with recurrent NAFLD. It has been suggested that AKM may play a protective role in the development of complications (such as de novo NAFLD) after LT [20]. However, Sun et al, found an increase in potentially beneficial bacteria, such as AKM, Blautia and Clostridiales cluster XIVa, 3 months after LT.…”

Section: Discussionmentioning

confidence: 99%

Alterations of gut bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii in late post-transplant period after liver transplantation

Kukov¹,

Peruhova²,

Syarov³

et al. 2022

Iberoam J Med

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Introduction: Recent studies have shown that the intestinal microbiota can modulate certain systemic metabolic and immune responses, including liver graft function and the development of complications in patients after liver transplantation (LT). Akkermansia muciniphila (AKM) and Faecalibacterium prausnitzii (FAEP) are two of the most abundant gut commensal bacteria, with mucosa-protective and anti-inflammatory effects that are important for maintaining normal intestinal homeostasis and gut barrier function. Our objective was to quantify levels of Akkermansia muciniphila and Faecalibacterium prausnitzii in immunosuppressed patients with LT. Materials and methods: Fecal samples from 23 liver transplant patients (15 adults and 8 children) and 9 non-LT controls were examined. Bacterial DNA was isolated from the samples using the stool DNA isolation kit and the obtained DNA was analyzed with commercially available qPCR kit for AKM and FAEP. Results: We found a statistically significant decrease in the amount of AKM and FAEP compared to the control group. The median values were: for AKM 8.75 for patients and 10.25 for the control group (p = 0.030), and for FAEP 9.72 and 10.47, p = 0.003, respectively. In children after LT, this difference was also statistically significant: AKM (p = 0.051) and FAEP (p = 0.014). In contrast no statistically significant differences were found between adult patients and controls, AKM (p = 0.283) and FAEP (p = 0.056), although the amount of both bacteria showed tendency for reduction. Conclusions: In this pilot study, we found a reduction in the total amount of the two studied bacteria in transplanted patients compared to the control healthy group.

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Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis

Abstract: Supplemental Digital Content is available in the text.

Cited by 18 publications

References 55 publications

Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases

Biliary Diseases from the Microbiome Perspective: How Microorganisms Could Change the Approach to Benign and Malignant Diseases

Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives

Alterations of gut bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii in late post-transplant period after liver transplantation

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