Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD.
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SUBMITTER: Lee G
PROVIDER: S-EPMC7536225 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Overweight and obesity are growing health problems in domestic cats, increasing the risks of insulin resistance, lipid dyscrasias, neoplasia, cardiovascular disease, and decreasing longevity. The signature of obesity in the feline gut microbiota has not been studied at the whole-genome metagenomic level. We performed whole-genome shotgun metagenomic sequencing in the fecal samples of eight overweight/obese and eight normal cats housed in the same research environment. We obtained 271 Gbp of sequences and generated a 961-Mbp de novo reference contig assembly, with 1.14 million annotated microbial genes. In the obese cat microbiome, we discovered a significant reduction in microbial diversity (P < 0.01) and Firmicutes abundance (P = 0.005), as well as decreased Firmicutes/Bacteroidetes ratios (P = 0.02), which is the inverse of obese human/mouse microbiota. Linear discriminant analysis and quantitative PCR (qPCR) validation revealed significant increases of Bifidobacterium sp., Olsenella provencensis, Dialister sp.CAG:486, and Campylobacter upsaliensis as the hallmark of obese microbiota among 400 enriched species, whereas 1,525 bacterial species have decreased abundance in the obese microbiome. Phascolarctobacterium succinatutens and an uncharacterized Erysipelotrichaceae bacterium are highly abundant (>0.05%) in the normal gut with over 400-fold depletion in the obese microbiome. Fatty acid synthesis-related pathways are significantly overrepresented in the obese compared with the normal cat microbiome. In conclusion, we discovered dramatically decreased microbial diversity in obese cat gut microbiota, suggesting potential dysbiosis. A panel of seven significantly altered, highly abundant species can serve as a microbiome indicator of obesity. Our findings in the obese cat microbiome composition, abundance, and functional capacities provide new insights into feline obesity. IMPORTANCE Obesity affects around 45% of domestic cats, and licensed drugs for treating feline obesity are lacking. Physical exercise and calorie restrictions are commonly used for weight loss but with limited efficacy. Through comprehensive analyses of normal and obese cat gut bacteria flora, we identified dramatic shifts in the obese gut microbiome, including four bacterial species significantly enriched and two species depleted in the obese cats. The key bacterial community and functional capacity alterations discovered from this study will inform new weight management strategies for obese cats, such as evaluations of specific diet formulas that alter the microbiome composition, and the development of prebiotics and probiotics that promote the increase of beneficial species and the depletion of obesity-associated species. Interestingly, these bacteria identified in our study were also reported to affect the weight loss success in human patients, suggesting translational potential in human obesity.
| S-EPMC9241680 | biostudies-literature
Project description:Betel nut chewing is associated with oral cancer, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (HCC). The aim of this study was to explore the association of betel nut chewing with liver fibrosis in subjects with and without nonalcoholic fatty liver disease (NAFLD). A total of 5967 subjects were enrolled. NAFLD was diagnosed with ultrasonography. Betel nut chewing was classified into non-chewing, ex-chewing, and current chewing, and cumulative dosages were calculated. The aspartate aminotransferase (AST)/platelet ratio index and NAFLD fibrosis scores (NFS) were calculated for evaluation of liver fibrosis. NAFLD increased the associated risk of liver fibrosis in those with (odds ratio (OR): 5.51, 95% confidence interval (CI): 3.09-9.80) and without betel nut chewing (OR: 2.33, 95% CI: 1.64-3.29). In subjects without NAFLD, betel nut chewing was not associated with liver fibrosis (OR: 1.12, 95% CI: 0.44-2.86). In subjects with NAFLD, cumulative betel nut chewing and ex- and current chewing were positively associated with NFS and significant liver fibrosis. In subjects with NAFLD, betel nut chewing, even ex-chewing, was associated with a higher risk of liver fibrosis, where higher cumulative levels were found to increase the risk of significant liver fibrosis. However, the associated risk of liver fibrosis due to betel nut chewing was insignificant in subjects without NAFLD.
| S-EPMC7998430 | biostudies-literature
Project description:BackgroundDietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS).AimTo determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms.MethodsFaecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways.ResultsAt baseline, 17 fructan-sensitive (vs 21 fructan-tolerant) subjects had lower alpha diversity (q < 0.05) and were enriched in the genus Holdermania. In contrast, fructan-tolerant subjects were enriched in 14 genera from the class Clostridia. During the fructan diet, fructan-sensitive (vs tolerant) subjects were enriched in both Agathobacter (P = 0.02) and Cyanobacteria (P = 0.0001). In contrast, fructan-tolerant subjects were enriched in three genera from the Clostridia class. Comparing the fructan vs maltodextrin diet, fructan-sensitive subjects had a significantly increased relative abundance of Bifidobacterium (P = 0.02) while fructan-tolerant subjects had increased Anaerostipes (P = 0.03) during the fructan diet. Only fructan-sensitive subjects had a trend towards increased predicted β-fructofuranosidase during the fructan vs maltodextrin diet.ConclusionsFructan-sensitive children with IBS have distinct gut microbiome signatures. These microbiome signatures differ both at baseline and in response to a fructan challenge.
| S-EPMC8281336 | biostudies-literature
Project description:Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12, I2 = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, I2 = 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20, I2 = 86%). At the genus level, lower relative proportions of Bifidobacterium and Eggerthella and higher Acidaminococcus, Anaerococcus, Catenibacterium, Dialister, Dorea, Escherichia-Shigella, Eubacterium, Fusobacterium, Megasphera, Prevotella, Roseburia, Streptococcus, and Sutterella were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.
| S-EPMC8746372 | biostudies-literature
Project description:BACKGROUND:Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS:We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites. A high-fat diet (HFD) intervention resulted in a rapid and significant increase in the intestinal BA pool within 12 h, followed by an alteration in microbial composition at 24 h, providing supporting evidence that BAs are major dietary factors regulating gut microbiota. Feeding mice with BAs along with a normal diet induced an obese phenotype and obesity-associated gut microbial composition, similar to HFD-fed mice. Inhibition of hepatic BA biosynthesis under HFD conditions attenuated the HFD-induced gut microbiome alterations. Both inhibition of BAs and direct suppression of microbiota improved obese phenotypes. CONCLUSIONS:Our study highlights a liver-BA-gut microbiome metabolic axis that drives significant modifications of BA and microbiota compositions capable of triggering metabolic disorders, suggesting new therapeutic strategies targeting BA metabolism for metabolic diseases.
| S-EPMC5731064 | biostudies-literature
Project description:BackgroundThere is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD.ObjectiveThe objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research.MethodsA total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways.ResultsIndependent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation.ConclusionPD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.
| S-EPMC5469442 | biostudies-literature
Project description:Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially those derived from the gut-microbiome, have a shared gene-effect with hepatic steatosis and fibrosis. This is a cross-sectional analysis of a prospective discovery cohort including 156 well-characterized twins and families with untargeted metabolome profiling assessment. Hepatic steatosis was assessed using magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis using MR-elastography (MRE). A twin additive genetics and unique environment effects (AE) model was used to estimate the shared gene-effect between metabolites and hepatic steatosis and fibrosis. The findings were validated in an independent prospective validation cohort of 156 participants with biopsy-proven NAFLD including shotgun metagenomics sequencing assessment in a subgroup of the cohort. In the discovery cohort, 56 metabolites including 6 microbial metabolites had a significant shared gene-effect with both hepatic steatosis and fibrosis after adjustment for age, sex and ethnicity. In the validation cohort, 6 metabolites were associated with advanced fibrosis. Among them, only one microbial metabolite, 3-(4-hydroxyphenyl)lactate, remained consistent and statistically significantly associated with liver fibrosis in the discovery and validation cohort (fold-change of higher-MRE versus lower-MRE: 1.78, P < 0.001 and of advanced versus no advanced fibrosis: 1.26, P = 0.037, respectively). The share genetic determination of 3-(4-hydroxyphenyl)lactate with hepatic steatosis was RG :0.57,95%CI:0.27-0.80, P < 0.001 and with fibrosis was RG :0.54,95%CI:0.036-1, P = 0.036. Pathway reconstruction linked 3-(4-hydroxyphenyl)lactate to several human gut-microbiome species. In the validation cohort, 3-(4-hydroxyphenyl)lactate was significantly correlated with the abundance of several gut-microbiome species, belonging only to Firmicutes, Bacteroidetes and Proteobacteria phyla, previously reported as associated with advanced fibrosis. Conclusion: This proof of concept study provides evidence of a link between the gut-microbiome and 3-(4-hydroxyphenyl)lactate that shares gene-effect with hepatic steatosis and fibrosis. (Hepatology 2018).
| S-EPMC6151296 | biostudies-literature
Project description:Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, the restoration of the gut microbiota and supplementation with commensal bacterial metabolites can be of therapeutic benefit against the disease. In this review, we summarize the roles of various bacterial metabolites in the pathogenesis of NAFLD and their therapeutic implications. The gut microbiota dysregulation is a feature of NAFLD, and the signatures of gut microbiota are associated with the severity of the disease through altered bacterial metabolites. Disturbance of bile acid metabolism leads to underactivation of bile acid receptors FXR and TGR5, causal for decreased energy expenditure, increased lipogenesis, increased bile acid synthesis and increased macrophage activity. Decreased production of butyrate results in increased intestinal inflammation, increased gut permeability, endotoxemia and systemic inflammation. Dysregulation of amino acids and choline also contributes to lipid accumulation and to a chronic inflammatory status. In some NAFLD patients, overproduction of ethanol produced by bacteria is responsible for hepatic inflammation. Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation and a fasting-mimicking diet have been applied to restore the gut microbiota for the improvement of NAFLD.
| S-EPMC7432372 | biostudies-literature
Project description:BackgroundObesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the faecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct microbiome species and their respective gene programs in obese individuals.MethodologyUsing shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n = 10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four investigatory or approved anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination.ResultsOnly sibutramine treatment induced consistent weight loss and improved glycaemic control in the obese rats. Weight loss was associated with reduced food intake and changes to the faecal microbiome in multiple microbial taxa, genes, and pathways. These include increased β-diversity, increased relative abundance of multiple Bacteroides species, increased Bacteroides/Firmicutes ratio and changes to abundance of genes and species associated with obesity-induced inflammation, particularly those encoding components of the flagellum and its assembly.ConclusionsSibutramine-induced weight loss in obese rats is associated with improved metabolic health, and changes to the faecal microbiome consistent with a reduction in obesity-induced bacterially-driven inflammation.
| S-EPMC8988407 | biostudies-literature
Project description:The increased consumption of various beverages has been paralleled by an epidemic of several intestinal diseases around the world, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and colorectal cancer. Mounting evidence have shown that excessive consumption of beverages increases the risk of IBD and IBS. In addition, sugar-sweeter, food additives and food ingredients were identified to play important roles in these conditions. Consuming cold beverage is common among some people, especially in the youngsters. However, whether the cold stress contribute directly to host metabolism, gut barrier and gut-brain axis is unclear. In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.
2024-06-21 | GSE178571 | GEO