Project description:Aim: To investigate the intestinal flora of nonalcoholic fatty liver disease (NAFLD) in Chinese children and adolescents using metagenomic approach. Methods: All participants underwent magnetic resonance spectroscopy (MRS) to quantify liver fat content. Hepatic steatosis was defined as MRS proton density fat fraction (MRS-PDFF) >5%. A total of 58 children and adolescents were enrolled in this study, including 25 obese NAFLD patients, 18 obese non-NAFLD children, and 15 healthy children. Stool samples were collected and analyzed with metagenomics. We used Shannon index to reflect the alpha diversities of gut microbiota. Wilcoxon rank sum test and Kruskal-Wallis test were performed to evaluate alpha diversities between groups. At last, the differences of gut microbiota composition and functional annotations between obese with and without NAFLD and healthy children were assessed by Kruskal-Wallis test. Results: Significant differences in gut microbiota composition and functional annotations among three groups of children and adolescents have been observed. Deep sequencing of gut microbiota revealed high abundance of phylum Proteobacteria (Gammaproteobacteria) in obese NAFLD patients, comparing with the control group. Overall, obese children without NAFLD had less abundant Helicobacter and Helicobacter pylori. Compared to the control group, in obese children with NAFLD, the abundance of Bacteroidetes (Alistipes) were significantly reduced. Faecalibacterium prausnitzii was the only species representing a difference between obese children with and without NAFLD. There were not significant differences in terms of alpha diversity among three groups. Functional annotations demonstrated that several pathways were differentially enriched between groups, including metabolism of other amino acids, replication and repair, folding, sorting, degradation, and glycan biosynthesis and metabolism. Conclusion: Significantly differences are observed in gut microbiota composition and functional annotations between obese children with and without NAFLD in comparison to the healthy children group. The characteristic of gut microbiota in this study may contribute to a further understanding the gut-liver axis of pediatric NAFLD in China.
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.
Project description:Reintroduction of the threatened red-crowned crane has been unsuccessful. Although gut microbiota correlates with host health, there is little information on gut microbiota of cranes under different conservation strategies. The study examined effects of captivity, artificial breeding and life stage on gut microbiota of red-crown cranes. The gut microbiotas of wild, captive adolescent, captive adult, artificially bred adolescent and artificially bred adult cranes were characterized by next-generation sequencing of 16S rRNA gene amplicons. The gut microbiotas were dominated by three phyla: Firmicutes (62.9%), Proteobacteria (29.9%) and Fusobacteria (9.6%). Bacilli dominated the 'core' community consisting of 198 operational taxonomic units (OTUs). Both captivity and artificial breeding influenced the structures and diversities microbiota of the gut. Especially, wild cranes had distinct compositions of gut microbiota from captive and artificially bred cranes. The greatest alpha diversity was found in captive cranes, while wild cranes had the least. According to the results of ordination analysis, influences of captivity and artificial breeding were greater than that of life stage. Overall, captivity and artificial breeding influenced the gut microbiota, potentially due to changes in diet, vaccination, antibiotics and living conditions. Metagenomics can serve as a supplementary non-invasive screening tool for disease control.
Project description:Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Fifty-seven patients with biopsy-proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F?2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F?2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F?2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F?2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F?2 were mostly related to carbohydrate, lipid, and amino acid metabolism.NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre-/probiotics therapies.
Project description:Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.
Project description:The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus <i>Ruminococcaceae</i> <i>UCG-010</i>, family <i>Ruminococcaceae</i>, order <i>Clostridiales</i>, and class <i>Clostridia</i> were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes<i>.</i> These results are different from research from western countries and could provide different targets for therapies by region.
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 <i>in vitro</i> 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.
Project description:Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and progresses to non-steatohepatitis (NASH) when the liver displays overt inflammatory damage. Increasing evidence has implicated critical roles for dysbiosis and microbiota-host interactions in NAFLD pathophysiology. In particular, microbiota alter intestine absorption of nutrients and intestine permeability, whose dysregulation enhances the delivery of nutrients, endotoxin, and microbiota metabolites to the liver and exacerbates hepatic fat deposition and inflammation. While how altered composition of gut microbiota attributes to NAFLD remains to be elucidated, microbiota metabolites are shown to be involved in the regulation of hepatocyte fat metabolism and liver inflammatory responses. In addition, intestinal microbes and circadian coordinately adjust metabolic regulation in different stages of life. During aging, altered composition of gut microbiota, along with circadian clock dysregulation, appears to contribute to increased incidence and/or severity of NAFLD.
Project description:Pathophysiological background in different phenotypes of nonalcoholic fatty liver disease (NAFLD) remains to be elucidated. The aim was to investigate the association between fecal and blood microbiota profiles and the presence of NAFLD in obese versus lean subjects. Demographic and clinical data were reviewed in 268 health checkup examinees, whose fecal and blood samples were available for microbiota analysis. NAFLD was diagnosed with ultrasonography, and subjects with NAFLD were further categorized as obese (body mass index (BMI) ?25) or lean (BMI <25). Fecal and blood microbiota communities were analyzed by sequencing of the V3-V4 domains of the 16S rRNA genes. Correlation between microbiota taxa and NAFLD was assessed using zero-inflated Gaussian mixture models, with adjustment of age, sex, and BMI, and Bonferroni correction. The NAFLD group (n = 76) showed a distinct bacterial community with a lower biodiversity and a far distant phylotype compared with the control group (n = 192). In the gut microbiota, the decrease in Desulfovibrionaceae was associated with NAFLD in the lean NAFLD group (log2 coefficient (coeff.) = -2.107, P = 1.60E-18), but not in the obese NAFLD group (log2 coeff. = 1.440, P = 1.36E-04). In the blood microbiota, Succinivibrionaceae showed opposite correlations in the lean (log2 coeff. = -1.349, P = 5.34E-06) and obese NAFLD groups (log2 coeff. = 2.215, P = 0.003). Notably, Leuconostocaceae was associated with the obese NAFLD in the gut (log2 coeff. = -1.168, P = 0.041) and blood (log2 coeff. = -2.250, P = 1.28E-10). In conclusion, fecal and blood microbiota profiles showed different patterns between subjects with obese and lean NAFLD, which might be potential biomarkers to discriminate diverse phenotypes of NAFLD.
Project description:Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-?, IL-6 and IFN-? were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD.