Disentangling the Progression of Non-alcoholic Fatty Liver Disease in the Human Gut Microbiota
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ABSTRACT:
SUBMITTER: Wang T
PROVIDER: S-EPMC8548776 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder worldwide. It comprises a spectrum of conditions that range from steatosis to non-alcoholic steatohepatitis, with progression to cirrhosis and hepatocellular carcinoma. Currently, there is no FDA-approved pharmacological treatment for NAFLD. The pathogenesis of NAFLD involves genetic and environmental/host factors, including those that cause changes in intestinal microbiota and their metabolites. In this review, we discuss recent findings on the relationship(s) of microbiota signature with severity of NAFLD and the role(s) microbial metabolites in NAFLD progression. We discuss how metabolites may affect NAFLD progression and their potential to serve as biomarkers for NAFLD diagnosis or therapeutic targets for disease management.
| S-EPMC7116620 | biostudies-literature
Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide, and gut microbes are associated with the development and progression of NAFLD. Despite numerous studies exploring the changes in gut microbes associated with NAFLD, there was no consistent pattern of changes.MethodWe retrieved studies on the human fecal microbiota sequenced by 16S rRNA gene amplification associated with NAFLD from the NCBI database up to April 2023, and re-analyzed them using bioinformatic methods.ResultsWe finally screened 12 relevant studies related to NAFLD, which included a total of 1,189 study subjects (NAFLD, n = 654; healthy control, n = 398; obesity, n = 137). Our results revealed a significant decrease in gut microbial diversity with the occurrence and progression of NAFLD (SMD = -0.32; 95% CI -0.42 to -0.21; p < 0.001). Alpha diversity and the increased abundance of several crucial genera, including Desulfovibrio, Negativibacillus, and Prevotella, can serve as an indication of their predictive risk ability for the occurrence and progression of NAFLD (all AUC > 0.7). The occurrence and progression of NAFLD are significantly associated with higher levels of LPS biosynthesis, tryptophan metabolism, glutathione metabolism, and lipid metabolism.ConclusionThis study elucidated gut microbes relevance to disease development and identified potential risk-associated microbes and functional pathways associated with NAFLD occurrence and progression.
| S-EPMC10797006 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.
| S-EPMC6893593 | biostudies-literature
Project description:The term, gut-liver axis, is used to highlight the close anatomical and functional relationship between the intestine and the liver. It has been increasingly recognized that the gut-liver axis plays an essential role in the development and progression of liver disease. In particular, in non-alcoholic fatty liver disease and alcohol-related liver disease, the two most common causes of chronic liver disease, a dysbiotic gut microbiota can influence intestinal permeability, allowing some pathogens or bacteria-derived factors from the gut reaching the liver through the enterohepatic circulation contributing to liver injury, steatohepatitis, and fibrosis progression. Pathways involved are multiple, including changes in bile acid metabolism, intestinal ethanol production, generation of short-chain fatty acids, and other by-products. Bile acids act through dedicated bile acid receptors, farnesoid X receptor and TGR5, in both the ileum and the liver, influencing lipid metabolism, inflammation, and fibrogenesis. Currently, both non-alcoholic fatty liver disease and alcohol-related liver disease lack effective therapies, and therapeutic targeting of gut microbiota and bile acids enterohepatic circulation holds promise. In this review, we summarize current knowledge about the role of gut microbiota in the pathogenesis of non-alcoholic fatty liver disease and alcohol-related liver disease, as well as the relevance of microbiota or bile acid-based approaches in the management of those liver diseases.
| S-EPMC7187400 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) remains an important health issue worldwide. The increasing prevalence of NAFLD is linked to type 2 diabetes (T2D). The gut microbiota is associated with the development of NAFLD and T2D. However, the relationship between gut microbiota and NAFLD severity has remained unclear in T2D patients. The aim of this study was to evaluate the relationship of gut microbiota with the severity of NAFLD in T2D patients. This cross-sectional study used transient elastography (FibroScan) to evaluate the severity of hepatic steatosis. We utilized qPCR to measure the abundance of Bacteroidetes, Firmicutes, Faecalibacterium prausnitzii, Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. Of 163 T2D patients, 83 with moderate to severe NAFLD had higher abundance of bacteria of the phylum Firmicutes with respect to 80 patients without NAFLD or with mild NAFLD. High abundance of the phylum Firmicutes increased the severity of NAFLD in T2D patients. A positive correlation between NAFLD severity and the phylum Firmicutes was found in T2D male patients with body mass index ≥24 kg/m2 and glycated hemoglobin <7.5%. Enrichment of the fecal microbiota with the phylum Firmicutes is significantly and positively associated with NAFLD severity in T2D patients. The gut microbiota is a potential predictor of NAFLD severity in T2D patients.
| S-EPMC8004607 | biostudies-literature
Project description:The development and progression of alcoholic fatty liver disease (AFLD) is influenced by the intestinal microbiota. Astaxanthin, a type of oxygenated carotenoid with strong antioxidant and anti-inflammatory properties, has been proven to relieve liver injury. However, the relationship between the gut microbiota regulation effect of astaxanthin and AFLD improvement remains unclear. The effects of astaxanthin on the AFLD phenotype, overall structure, and composition of gut microbiota were assessed in ethanol-fed C57BL/6J mice. The results showed that astaxanthin treatment significantly relieves inflammation and decreases excessive lipid accumulation and serum markers of liver injury. Furthermore, astaxanthin was shown to significantly decrease species from the phyla Bacteroidetes and Proteobacteria and the genera Butyricimonas, Bilophila, and Parabacteroides, as well as increase species from Verrucomicrobia and Akkermansia compared with the Et (ethanol)group. Thirteen phylotypes related to inflammation as well as correlated with metabolic parameters were significantly altered by ethanol, and then notably reversed by astaxanthin. Additionally, astaxanthin altered 18 and 128 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways involved in lipid metabolism and xenobiotic biodegradation and metabolism at levels 2 and 3, respectively. These findings suggest that Aakkermansia may be a potential target for the astaxanthin-induced alleviation of AFLD and may be a potential treatment for bacterial disorders induced by AFLD.
| S-EPMC6164583 | biostudies-literature
Project description:Background & Aims: Non-alcoholic fatty liver disease (NALFLD)-associated changes in gut microbiota are important drivers of disease progression toward fibrosis. Therefore, reversing microbiota alterations could ameliorate NAFLD progression. Oat beta-glucan, a non-digestible polysaccharides, has shown promising therapeutic effects on hyperlipidemia associated with NAFLD, but its impact on gut microbiota and most importantly NAFLD fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping including body composition, glucose tolerance, and lipid metabolism as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of NAFLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota was modulated using broad-spectrum antibiotic (Abx) treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened NAFLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon Abx treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of TLR ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced NAFLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing NAFLD progression and should be assessed in clinical studies.
2024-01-01 | GSE246738 | GEO
Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract.MethodsRats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites.ResultThe VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively.ConclusionVD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.
| S-EPMC9932697 | biostudies-literature
Project description:Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.
| S-EPMC7833443 | biostudies-literature
Project description:Resveratrol (RSV) is a potential alternative therapy for non-alcoholic fatty liver disease (NAFLD) that has been evaluated in many clinical trials, but the mechanisms of RSV action have not been fully elucidated. Recent studies suggested that the gut microbiota is an important RSV target; therefore, we speculated that the gut microbiota might mediate the beneficial effects of RSV in NAFLD. To verify this hypothesis, we established a high-fat diet (HFD)-induced NAFLD mouse model, which was subjected to RSV gavage to evaluate the therapeutic effects. We observed that RSV reduced liver steatosis and insulin resistance in NAFLD. RSV significantly changed the diversity and composition of the gut microbiota according to 16S rRNA sequencing. Gut microbiota gene function prediction showed that the enrichment of pathways related to lipid and glucose metabolism decreased after RSV treatment. Furthermore, correlation analysis indicated that the improvements in NAFLD metabolic indicators were closely related to the altered gut microbiota. We further fermented RSV with the gut microbiota in vitro to verify that RSV directly affected the gut microbiota. Our data suggested that the gut microbiota might be an important target through which RSV exerts its anti-NAFLD effect.
| S-EPMC7942199 | biostudies-literature