A Nine-Strain Bacterial Consortium Improves Portal Hypertension and Insulin Signaling and Delays NAFLD Progression In Vivo (original) (raw)
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Hepatology (Baltimore, Md.), 2017
Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) has been scarcely studied. Our aim was to investigate the role of IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages: Stage 1: Sprague-Dawley rats were fed for 8 weeks with high-fat diet and high-glucose/fructose syrup (HFGFD) or control diet/water (CD). Representative rats were selected as IM donors for Stage 2. Stage 2: additional HFGFD and CD rats underwent intestinal decontamination followed by IM transplantation with faeces from opposite diet donors (heterologous transplant, Tr) or autologous faecal transplant (Atr) ((as controls)), generating four groups: CD-Atr, CD-Tr, HFGFD-Atr, HFGFD-Tr. After IM transplantation, the original diet was maintained for 12-14 days until euthanasia.HFGFD rats developed obesity, insulin r...
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.
The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies
2024
One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.
Cells
Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of...
Gut–liver axis: The impact of gut microbiota on non alcoholic fatty liver disease
Nutrition, Metabolism and Cardiovascular Diseases, 2012
Aim: To examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis. Data synthesis: Emerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of guteliver axis health. Disturbances in the homeostasis between bacteria-and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster "bacterial translocation", defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20e75%) of patients with chronic liver disease. In addition, evidence implicating the guteliver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years. Conclusions: Complex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD. ª
Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.
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.
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.