Fecal SCFAs and SCFA‐producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T‐cell activation and advanced disease (original) (raw)
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International Journal of Scientific Research and Management
Background and aim: The aim of this study was to evaluate the role of gut microbiota with wide variety of clinical manifestations of patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Methods: The study enrolled 133 cases of patients with NAFLD/NASH who were diagnosed at Enmedic Clinic, Tbilisi/Georgia and carried out between May 2017 and May 2021. Patients were 21-65 years of age attending our clinic. Patients were diagnosed with NASH/NAFLD based on fibroscan of liver and ultrasound investigation, and additionaly for NASH with raised serum alanine aminotransferase (ALT) and aspartat aminotrasnferase (AST) levels greater than upper limit of normal (40 IU/ ml). Trial profile of patients is shown on figure 1. 10 patients loss follow up The 123 patients were divided into three groups. Group A (61 patients) was diagnosed with NAFLD, the 42 patients of group B were diagnosed with NASH and group C (control) were 20 healthy volunteers. Res...
Gut microbiome and nonalcoholic fatty liver diseases
Pediatric Research, 2014
Review nature publishing group We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/ NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction.
Alimentary Pharmacology & Therapeutics, 2019
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.
Gut Microbiota in NAFLD Pathogenesis and Possible Dietary-Based Strategies
2020
Nonalcoholic fatty liver disease (NAFLD) is considered as a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It entails a broad spectrum of hepatic injuries, which includes simple and uncomplicated steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and physical activity) and inherited (i.e., genetic/epigenetic) risk factors. Emerging evidence has outlined the implication of intestinal microbiota and its harmful by-products as actively contributors to NAFLD pathophysiology, probably due to the tight anatomo-functional crosstalk between the gut and the liver. Unhealthy dietary habits may trigger qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal bar...
Background The human gut microbiota (GM) is a diverse ecosystem crucial for health, impacting physiological processes across the host's body. This review highlights the GM's involvement in Non-Alcoholic Fatty Liver Disease (NAFLD) and explores its diagnosis, treatment, and management. Main Text The GM influences gut functionality, digestion, immunity, and more. Short-chain fatty acids (SCFAs), produced by microbial fermentation, regulate metabolism, inflammation, and immune responses. Bile acids (BAs) modulate the microbiome and liver functions, affecting NAFLD progression. Dysbiosis and increased gut permeability contribute to NAFLD through bacterial components and metabolites reaching the liver, causing inflammation and oxidative stress. The microbiome's impact on immune cells further exacerbates liver damage. Symptoms of NAFLD can be subtle or absent, making diagnosis challenging. Imaging techniques assist in diagnosing and staging NAFLD, but liver biopsy remains vital for accurate assessment. Promising treatments include FXR agonists, GLP-1 agonists, and FGF19 and FGF21 mimetics, targeting various pathways associated with NAFLD pathogenesis. Fecal Microbiota Transplantation (FMT) emerges as a potential therapeutic avenue to restore gut microbiota diversity and alleviate NAFLD. Lifestyle interventions, such as dietary modifications, exercise, and probiotics, also play a pivotal role in managing NAFLD and restoring gut health. Conclusion Despite significant progress, the complex interplay between the gut microbiome, NAFLD, and potential treatments necessitates further research to unravel underlying mechanisms and develop effective therapeutic strategies.
Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty Liver Disease
Mediators of Inflammation
The prevalence of nonalcoholic fatty liver disease and the consequent burden of metabolic syndrome have increased in recent years. Although the pathogenesis of nonalcoholic fatty liver disease is not completely understood, it is thought to be the hepatic manifestation of the dysregulation of insulin-dependent pathways leading to insulin resistance and adipose tissue accumulation in the liver. Recently, the gut-liver axis has been proposed as a key player in the pathogenesis of NAFLD, as the passage of bacteria-derived products into the portal circulation could lead to a trigger of innate immunity, which in turn leads to liver inflammation. Additionally, higher prevalence of intestinal dysbiosis, larger production of endogenous ethanol, and higher prevalence of increased intestinal permeability and bacterial translocation were found in patients with liver injury. In this review, we describe the role of intestinal dysbiosis in the activation of the inflammatory cascade in NAFLD.
Gut Microbiota: Association with NAFLD and Metabolic Disturbances
BioMed Research International, 2015
Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gut microbiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gut microbiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.
The role of the gut microbiota in nonalcoholic fatty liver disease
Nature Reviews Gastroenterology & Hepatology, 2010
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence increases with increasing rates of obesity, insulin resistance, and diabetes mellitus. The pathogenesis of NAFLD involves many factors, including the gastrointestinal microbiota. However, there is still debate about the impact of gut dysbiosis in the NAFLD disease progression. Therefore, this paper aims to review the relationship between gut microbiota and other risk factors for NAFLD and how gut dysbiosis plays a role in the pathogenesis of NAFLD. Hopefully, this paper can make an appropriate contribution to the development of NAFLD research in the future.
International journal of molecular medicine, 2018
Several mechanisms contribute to the pathogenesis of non‑alcoholic fatty liver disease (NAFLD). The intestinal microbiota (IM) and liver immune cells (LIC) may serve a role, but there has been no previous study assessing potential associations between IM and LIC. The aim of the present study was to investigate whether there are differences in LIC markers between patients with NAFLD and healthy controls (HC), and to determine whether these markers are associated with specific IM. The present prospective, cross‑sectional study examined a cohort of adults with liver biopsy‑confirmed NAFLD and HC. Clinical and laboratory data were collected. Fecal IM was assessed by quantitative polymerase chain reaction and LIC, by immunohistochemistry. NAFLD activity score (NAS) was used for disease severity. Liver immune cell counts were increased in patients with NAFLD (n=34) vs. HC (n=8) and this was associated with disease severity. Hematopoietic cell marker cluster of differentiation (CD)45+ and ...