Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives

Abstract

Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient’s gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.

Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions

“…The relationship among gut microbiota alteration, liver fibrosis and portal hypertension is similar to the question of the chicken and the egg, as they drive and affect each other[ 75 ]. Compared with compensated cirrhosis, gut microbiota composition is characterized by an increase in the abundance of potentially pathogenic bacteria in the decompensation stage, especially Alcaligenaceae , Porphyromonadaceae , Veillonellaceae and Enterobacteriaceae [ 76 ].…”

“…On the one hand, gut microbiota alteration in the decompensation stage is consistent with the accumulation of microbe-derived products, including ammonia, mercaptans, benzodiazepine-like substances, and indoles[ 76 ]. These products can pass the blood-brain barrier and alter astrocyte function, resulting in osmotic or oxidative stress, mitochondrial dysfunction, neurotransmission disorder, etc.…”

“…Fecal microbiota transplantation (FMT) is an emerging treatment method that transfers the gut microbiota from a healthy donor to a patient[ 123 ]. Due to its ability to directly reshape or rebuild the recipient’s gut microbial communities, FMT is one of the most promising therapies balancing and stabilizing the gut microbiota[ 76 ], and it has been applied to research-based treatment in animal models of a variety of diseases[ 124 , 125 ] and to study the mechanisms[ 126 , 127 ]. In recent years, FMT has been expanded to clinical treatment for human disease as a noninvasive strategy for conditions including recurrent Clostridium difficile infection[ 128 ], inflammatory bowel disease[ 129 ], severe obesity and metabolic syndrome[ 130 ].…”

Fecal Microbiota Transplantation in Decompensated Cirrhosis: A Systematic Review on Safety and Efficacy

“…Limitations to widespread FMT use despite promising outcomes is likely due to the lack of large, well-designed studies; one such example is the use of FMT in cirrhotic patients. In recent years, the therapeutic role of FMT in the cirrhotic population Antibiotics 2022, 11, 838 2 of 11 has become more prominently discussed, as new research hypothesizes that underlying intestinal dysbiosis may play a fundamental role in worsening clinical status in such patients [1][2][3][4][5]. Although the pathogenesis is still unclear, new research hypothesizes that "portal hypertension, reduced secretion of gastric acid, impaired gastrointestinal motility, and local and systemic immunological dysfunction" are the primary factors contributing to gut microbiota derangements that lead to increase in pathogenic bacteria and decrease in commensal bacteria [2].…”

“…In recent years, the therapeutic role of FMT in the cirrhotic population Antibiotics 2022, 11, 838 2 of 11 has become more prominently discussed, as new research hypothesizes that underlying intestinal dysbiosis may play a fundamental role in worsening clinical status in such patients [1][2][3][4][5]. Although the pathogenesis is still unclear, new research hypothesizes that "portal hypertension, reduced secretion of gastric acid, impaired gastrointestinal motility, and local and systemic immunological dysfunction" are the primary factors contributing to gut microbiota derangements that lead to increase in pathogenic bacteria and decrease in commensal bacteria [2]. This further causes inflammation and damage along the intestinal membrane, allowing for translocation of bacteria and bacteria-derived byproducts such as ammonia which can further trigger liver injury and systemic inflammation and can lead to decompensation in cirrhotic patients such as hepatic encephalopathy [3].…”