Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

Advanced Science, Год журнала: 2022, Номер 9(11)

Опубликована: Фев. 7, 2022

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including microbiome. To decipher hepatic steatosis (HS) pathogenesis excluding critical confounding variants diabetes, 56 heterogenous MAFLD patients are characterized generating multiomics data oral gut metagenomics as well plasma metabolomics inflammatory proteomics data. The dysbiosis microbiome explored host-microbiome based on global metabolic revealed. These integrated using network HS's key features identified HS finally predicted these findings validated follow-up cohort, where 22 subjects with varying degree of characterized.

Язык: Английский

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Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity

Cell Reports Medicine, Год журнала: 2023, Номер 4(12), С. 101341 - 101341

Опубликована: Дек. 1, 2023

The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for microbiota, scavenging it from host. Its role in NAFLD poorly known. Plasma metabolomics, transcriptomics, and fecal metagenomics were performed three human cohorts coupled with hepatocyte, rodent, Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated steatosis linked hepatic transcriptomic signature involved insulin signaling, inflammation, trace amine-associated receptor 1. Circulating was Proteobacteria positively bacteria lacking utilization (Hut) system. supplementation improved different animal models (diet-induced mouse flies, ob/ob mouse, ovariectomized rats) reduced de novo lipogenesis. Fecal transplantation (FMT) low-histidine donors mono-colonization germ-free flies Enterobacter cloacae increased triglyceride accumulation content. interplay among catabolism, opens therapeutic opportunities.

Язык: Английский

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Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Май 10, 2024

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific and underlying mechanism involved CKD-VC. identified increased abundance Prevotella copri (P. copri) feces CKD rats (induced by using 5/6 nephrectomy followed a high calcium phosphate diet) with aortic via amplicon sequencing 16S rRNA genes. In patients CKD, we further confirmed positive correlation between P. scores. Moreover, oral administration live aggravated CKD-related VC osteogenic differentiation smooth muscle cells vivo, accompanied intestinal destruction, enhanced expression Toll-like receptor-4 (TLR4), elevated lipopolysaccharide (LPS) levels. vitro ex vivo experiments consistently demonstrated copri-derived LPS (Pc-LPS) accelerated phosphate-induced VSMC differentiation. Mechanistically, Pc-LPS bound TLR4, then activated nuclear factor κB (NF-κB) nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome signals during VC. Inhibition NF-κB reduced NLRP3 attenuated Pc-LPS-induced calcification. Our study clarifies novel VC, mechanisms involving inflammation-regulating metabolites including Pc-LPS, activation NF-κB/NLRP3 signaling pathway. These findings highlight its-derived as potential therapeutic targets for CKD.

Язык: Английский

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Pharmacological treatment for metabolic dysfunction–associated steatotic liver disease and related disorders: Current and emerging therapeutic options

Pharmacological Reviews, Год журнала: 2025, Номер 77(2), С. 100018 - 100018

Опубликована: Янв. 7, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty disease) is a chronic affecting over billion individuals worldwide. MASLD can gradually develop into more severe pathologies, including metabolic steatohepatitis (MASH), cirrhosis, and malignancy. Notably, although being global health problem, there are very limited therapeutic options against its related diseases. While thyroid hormone receptor agonist (resmetirom) recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in incidence, it urgent novel effective strategies prevalent In this article, pathogenic mechanisms of MASH, insulin resistance, dysregulated nuclear signaling, genetic risk factors (eg, patatin-like phospholipase domain-containing 3 hydroxysteroid 17-β dehydrogenase-13), introduced. Various interventions then explored, medication (resmetirom), drugs that currently clinical trials glucagon-like peptide 1 agonist, fibroblast growth factor 21 analog, PPAR agonist), those failed previous obeticholic acid stearoyl-CoA desaturase antagonist). Moreover, given role gut microbes increasingly acknowledged, alterations microbiota microbial development elucidated. Therapeutic approaches target dietary intervention probiotics) further explored. With better understanding multifaceted mechanisms, innovative therapeutics root causes greatly facilitated. The possibility alleviating achieving patient outcomes within reach. SIGNIFICANCE STATEMENT: (MASLD) most common worldwide, progress steatohepatitis, cancer. Better has facilitated strategies. increasing evidence illustrated crucial pathogenesis It may be clinically feasible alleviate future.

Язык: Английский

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A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non‐alcoholic steatohepatitis in subjects with obesity

Journal of Gastroenterology and Hepatology, Год журнала: 2023, Номер 38(5), С. 791 - 799

Опубликована: Фев. 18, 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of disease. Increasing evidence indicates that gut microbiota can play an important role in pathophysiology NAFLD. Recently, several studies have tested predictive value microbiome profiles NAFLD progression; however, comparisons microbial signatures or non-alcoholic steatohepatitis (NASH) produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed characterize metagenome composition patients with disease.Gut 45 well-characterized obesity biopsy-proven was evaluated using shot-gun sequencing: 11 controls (non-NAFL), liver, 23 NASH.Our study showed Parabacteroides distasonis Alistipes putredenis were enriched but not NASH patients. Notably, a hierarchical clustering analysis, differentially distributed among groups, membership Prevotella copri dominant cluster associated greater risk developing NASH. Functional analyses although no differences LPS biosynthesis pathways observed, Prevotella-dominant subjects had higher circulating levels lower abundance encoding butyrate production.Our findings suggest bacterial community for progression, probably linked intestinal permeability capacity production.

Язык: Английский

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Gut microbiome and metabolome signatures in liver cirrhosis-related complications

Clinical and Molecular Hepatology, Год журнала: 2024, Номер 30(4), С. 845 - 862

Опубликована: Июль 25, 2024

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent metabolic signatures patients cirrhosis.Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls 142 patients) via V3-V4 16S rRNA sequencing. Next, 51 (17 34 were selected for fecal metabolite gas chromatography mass spectrometry liquid coupled to time-of-flight spectrometry. Correlation analyses targeting gut-microbiota, metabolites, clinical parameters, presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, deceased).Results: <i>Veillonella</i> bacteria, <i>Ruminococcus gnavus</i>, <i>Streptococcus pneumoniae</i> cirrhosis-related microbiotas compared control group. <i>Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium</i>, <i>Hungatella</i>_uc associated The areas under receiver operating characteristic curve (AUROCs) diagnosis cirrhosis, deceased 0.863, 0.733, 0.71, 0.69, respectively. AUROCs mixed microbial species complication 0.808 0.847, According profile, 5 increased biomarkers (AUROC >0.880) Clinical markers significantly correlated metabolites.Conclusions: Cirrhosis-dependent present unique that can be used as noninvasive its

Язык: Английский

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Lactobacillus acidophilus ameliorates cholestatic liver injury through inhibiting bile acid synthesis and promoting bile acid excretion

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Авг. 29, 2024

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was examine effects and

Язык: Английский

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The Effects of Alcohol Drinking on Oral Microbiota in the Chinese Population

International Journal of Environmental Research and Public Health, Год журнала: 2022, Номер 19(9), С. 5729 - 5729

Опубликована: Май 8, 2022

The dysbiosis of oral microbiota is linked to numerous diseases and associated with personal lifestyles, such as alcohol drinking. However, there inadequate data study the effect drinking on from Chinese population. Here, we profiled 150 healthy subjects in population by 16S rRNA gene sequencing. results showed that drinkers had significantly higher alpha diversity than non-drinkers. A significant difference overall composition was observed between non-drinkers drinkers. Additionally, using DESeq analysis, found genus Prevotella Moryella, species melaninogenica tannerae were enriched drinkers; meanwhile, Lautropia, Haemophilus Porphyromonas, parainfluenzae depleted PICRUSt analysis different genera mainly related metabolism pathways. oxygen-independent pathways, including galactose, fructose mannose positively while pyruvate pathway, an aerobic decreased negatively Our suggested may affect health altering microbial potentially affecting functional These findings have implications for better understanding potential role those bacteria play alcohol-related diseases.

Язык: Английский

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Accumulation of Black Carbon Particles in Placenta, Cord Blood, and Childhood Urine in Association with the Intestinal Microbiome Diversity and Composition in Four- to Six-Year-Old Children in the ENVIR ON AGE Birth Cohort

Environmental Health Perspectives, Год журнала: 2023, Номер 131(1)

Опубликована: Янв. 1, 2023

Background: The gut microbiome plays an essential role in human health. Despite the link between air pollution exposure and various diseases, its association with during susceptible life periods remains scarce. Objectives: In this study, we examined black carbon particles quantified prenatal postnatal biological matrices bacterial richness diversity measures, families. Methods: A total of 85 stool samples were collected from 4- to 6-y-old children enrolled ENVIRonmental influence ON early AGEing birth cohort. We performed 16S rRNA gene sequencing calculate indices (Chao1 richness, Shannon diversity, Simpson diversity) relative abundance Black via white light generation under femtosecond pulsed laser illumination placental tissue cord blood, employed as biomarkers, urine, used a post-natal biomarker. robust multivariable-adjusted linear models examine associations loads measures index) (Shannon indices), adjusting for parity, season delivery, batch, age, sex, weight height child, maternal education. Additionally, differential analysis families correction sampling fraction bias. Results are expressed percentage difference doubling 95% confidence interval (CI). Results: Two negatively associated [Shannon: −4.38% (95% CI: −8.31%, −0.28%); Simpson: −0.90% −1.76%, −0.04%)], blood −3.38% −5.66%, −0.84%); −0.91 −1.66%, −0.16%)], urinary −3.39% −5.77%, −0.94%); −0.89% −1.37%, −0.40%)]. explained variance on above varied 6.1% 16.6%. No statistically significant found load Chao1 index. After multiple testing correction, was Defluviitaleaceae Marinifilaceae, Christensenellaceae Coriobacteriaceae; not after correction. Conclusion: composition childhood intestinal microbiome. These findings address influential pregnancy https://doi.org/10.1289/EHP11257

Язык: Английский

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Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(20), С. 15272 - 15272

Опубликована: Окт. 17, 2023

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic worldwide, affecting nearly 25% of global adult population. Increasing evidence suggests that functional and compositional changes in gut microbiota may contribute to development promote progression NAFLD. 16S rRNA gene next-generation sequencing widely used determine specific features NAFLD microbiome, but a complex system such as requires comprehensive approach. We three different approaches: MALDI-TOF-MS bacterial cultures, qPCR, NGS sequencing, well wide variety statistical methods assess differences composition between patients without significant fibrosis control group. The listed showed enrichment Collinsella sp. Oscillospiraceae for samples Lachnospiraceae (and particular Dorea sp.) Veillonellaceae families, Bifidobacteriaceae, Lactobacillaceae, Enterococcaceae (particularly Enterococcus faecium faecalis), were also found be important taxa microbiome evaluation. Considering individual method observations, an increase Candida krusei decrease Bacteroides uniformis detected using MALDI-TOF-MS. An Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, Comamonadaceae, Acidaminococcaceae observed with NGS, Fusobacterium nucleatum was shown qPCR analysis. These findings confirm associated composition. Further investigations are required cause-and-effect relationships impact microbiota-derived compounds on

Язык: Английский

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