Immune cell-mediated features of non-alcoholic steatohepatitis

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 429 - 443

Published: Nov. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Language: Английский

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Gut-liver axis: Pathophysiological concepts and clinical implications

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1700 - 1718

Published: Oct. 7, 2022

Language: Английский

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Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 704 - 712

Published: Feb. 28, 2022

Abstract Previous studies have suggested that the gut microbiome influences response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product we postulated could augment CPI through modulation of microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive metastatic renal cell carcinoma clear and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 receive nivolumab ipilimumab without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint compare relative abundance Bifidobacterium spp. baseline 12 weeks not met, no significant differences Shannon index associated addition nivolumab–ipilimumab detected. Secondary endpoints included rate, progression-free survival (PFS) toxicity. PFS significantly longer receiving than (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05–0.47, P = 0.001). Although statistically significant, rate also higher (58% 20%, 0.06). No difference toxicity observed between arms. data suggest appears enhance clinical outcome treated nivolumab–ipilimumab. Larger are warranted confirm observation elucidate mechanism action effects on immune compartments.

Language: Английский

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Role of the gut microbiota in type 2 diabetes and related diseases

Metabolism, Journal Year: 2021, Volume and Issue: 117, P. 154712 - 154712

Published: Jan. 23, 2021

Language: Английский

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Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 1, 2021

The gut bacterium

Language: Английский

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Short-chain fatty acids in diseases

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 18, 2023

Abstract Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in gastrointestinal tract. The absorption SCFAs is mediated substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled 1, which promote cellular metabolism. An increasing number studies have implicated microorganisms crucial executors diet-based microbial influence on host. important fuels for intestinal epithelial cells (IECs) represent a major carbon flux from diet, that decomposed gut microbiota. play vital role multiple molecular biological processes, promoting secretion glucagon-like peptide-1 IECs to inhibit elevation blood glucose, expression G protein-coupled receptors GPR41 GPR43, inhibiting histone deacetylases, participate regulation proliferation, differentiation, function IECs. affect motility, barrier function, host Furthermore, regulatory roles local, intermediate, peripheral metabolisms. Acetate, propionate, butyrate SCFAs, they involved immunity, apoptosis, inflammation, lipid Herein, we review diverse functional this class reflect their ability intestine, metabolic, other diseases.

Language: Английский

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Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives

Biomolecules, Journal Year: 2021, Volume and Issue: 12(1), P. 56 - 56

Published: Dec. 31, 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis present. represents complex process implicating numerous factors—genetic, metabolic, dietary—intertwined in multi-hit etiopathogenetic model. Recent data have highlighted role gut dysbiosis, may render bowel more permeable, leading increased free acid absorption, bacterial migration, parallel release toxic products, lipopolysaccharide (LPS), proinflammatory cytokines that initiate sustain inflammation. Although dysbiosis present each stage, there currently no single microbial signature distinguish or predict patients will from NASH HCC. Using 16S rRNA sequencing, majority with NAFLD/NASH exhibit numbers Bacteroidetes differences presence Firmicutes, resulting decreased F/B ratio studies. They also an proportion species belonging Clostridium, Anaerobacter, Streptococcus, Escherichia, Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, Alistipes spp. are less prominent. In comparison healthy controls, show higher abundance Proteobacteria, Enterobacteriaceae, Escherichia spp., while Faecalibacterium prausnitzii Akkermansia muciniphila diminished. Children Oscillospira accompanied by elevated Dorea, Blautia, Prevotella copri, Ruminococcus Gut microbiota composition vary between population groups different stages NAFLD, making any conclusive causative claims about profiles challenging. Moreover, various metabolites be involved pathogenesis such short-chain acids, lipopolysaccharide, bile choline trimethylamine-N-oxide, ammonia. this review, we summarize microbiome pathogenesis, discuss potential preventive therapeutic interventions related microbiome, administration probiotics, prebiotics, synbiotics, antibiotics, bacteriophages, well contribution bariatric surgery fecal transplantation armamentarium against NAFLD. Larger longer-term prospective studies, including well-defined cohorts multi-omics approach, required better identify associations metabolites, occurrence progression.

Language: Английский

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Gut–liver axis: barriers and functional circuits

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(7), P. 447 - 461

Published: April 21, 2023

Language: Английский

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New Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 13, 2021

The interaction between host and microorganism widely affects the immune metabolic status. Indole its derivatives are metabolites produced by metabolism of tryptophan catalyzed intestinal microorganisms. By activating nuclear receptors, regulating hormones, affecting biological effects bacteria as signaling molecules, indole maintain homeostasis impact liver response, which shows good therapeutic prospects. We reviewed recent studies on derivatives, including related metabolism, influence diets commensal bacteria, targets mechanisms in pathological conditions, especially progress strategies. New research insights into indoles will facilitate a better understanding their druggability application diseases.

Language: Английский

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Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 10, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of tumor-related mortality worldwide. In recent years, emergency immune checkpoint inhibitor (ICI) has revolutionized management HCC. Especially, combination atezolizumab (anti-PD1) bevacizumab (anti-VEGF) been approved by FDA as first-line treatment for advanced Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing drug resistance frequent recurrence. The tumor microenvironment (TME) complex structured mixture characterized abnormal angiogenesis, chronic inflammation, dysregulated extracellular matrix (ECM) remodeling, collectively contributing immunosuppressive milieu that turn prompts proliferation, invasion, metastasis. coexists interacts with various cells maintain development It widely accepted dysfunctional tumor-immune ecosystem can lead failure surveillance. TME an external evasion consisting 1) cells; 2) co-inhibitory signals; 3) soluble cytokines signaling cascades; 4) metabolically hostile microenvironment; 5) gut microbiota affects microenvironment. Importantly, effectiveness immunotherapy largely depends on (TIME). Also, metabolism profoundly affect Understanding how progression will contribute better preventing HCC-specific overcoming already developed therapies. this review, we mainly introduce underlying role microenvironment, describe dynamic interaction microbiome, propose therapeutic strategies manipulate favor more effective immunotherapy.

Language: Английский

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