Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(11), P. 1006 - 1020

Published: July 5, 2024

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, fungi. In addition, shows potential as biomarker for early HCC diagnosis assessing efficacy of immunotherapy unresectable HCC. This review examines how microbiota dysbiosis, with varied functional profiles, contributes to HCCs different etiologies. We discuss therapeutic strategies modulate including diets, antibiotics, probiotics, fecal transplantation, nano-delivery systems, underscore their an adjunctive treatment modality

Language: Английский

---

Radiotherapy plus a self-gelation powder encapsulating tRF5-GlyGCC inhibitor potentiates natural kill cell immunity to prevent hepatocellular carcinoma recurrence

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 10, 2025

Abstract Hepatocellular carcinoma (HCC) recurrence postresection represents a thorny problem in clinical practice, of which impaired natural killer (NK) cell cytotoxicity one crucial causes. Apart from recurrence, hepatectomy-induced abdominal adhesion also poses huge challenges such as pain, intestinal obstruction, and perforation. Evidence demonstrates that radiotherapy can upregulate NK group 2D ligand expression on tumor cells to enhance cytotoxicity, indicating its great potential curbing HCC recurrence. Nevertheless, has been disclosed incur suppression antitumor immunity. Herein, we reveal glycocholic acid (GCA)/tRNA-derived fragment 5 (tRF5)-GlyGCC signaling axis is activated mouse model after radiotherapy, dampens immunity limit therapeutic efficacy. Mechanistically, tRF5-GlyGCC interact with KDM6B epigenetically Runx2 then transcriptionally activate ITGBL1 S100A9 cells, further reduces directly attracts myeloid-derived suppressor (MDSC) inhibit function indirectly, respectively. Therefore, plus targeting may be an optimized postoperative adjuvant therapy against Then, nanocomposite powder designed for liver-localized delivery inhibitor. After sprayed liver resection margin model, this rapidly form in-situ Janus-adhesive hydrogel, allows sustained Importantly, it synergize potentiate prevent postresection. Moreover, application surgical bed effectively mitigates rat hepatectomy model. Altogether, our work develops tRF5-GlyGCC-targeting power sensitizing thwart preventing adhesion. Graphical

Language: Английский

---

Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 19

Published: Dec. 23, 2023

Hepatocellular carcinoma (HCC) is a prevalent and aggressive liver malignancy. The interplay between bile acids (BAs) the gut microbiota has emerged as critical factor in HCC development progression. Under normal conditions, BA metabolism tightly regulated through bidirectional microorganisms BAs. plays role metabolism, BAs are endogenous signaling molecules that help maintain intestinal homeostasis. Of note, dysbiotic changes during pathogenesis cancer can disrupt homeostasis, thereby leading to inflammation fibrosis, ultimately contributing development. Therefore, understanding intricate crucial for elucidating mechanisms underlying hepatocarcinogenesis. In this review, we comprehensively explore roles functions of with focus on interactions HCC. Additionally, therapeutic strategies targeting discussed, including use agonists/antagonists, probiotic/prebiotic dietary interventions, fecal transplantation, engineered bacteria. summary, complex BA-microbiota crosstalk provide valuable insights into facilitate innovative approaches

Language: Английский

---

Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 84 - 84

Published: Jan. 9, 2025

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of tumorigenesis. Due to the obesity epidemics, occurrence NAFLD has significantly increased nearly 30% prevalence worldwide. HCC often arises in background chronic (CLD), such nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked progression development, investigations reporting crucial role for gut-liver axis microbial metabolites promoting CLD. Moreover, GM affects homeostasis, energy status, immune microenvironment, influencing response immunotherapy interesting therapeutic implications. In this review, we summarize main changes derived (e.g., short-chain acids bile acids) occurring patients progression, emphasizing their potential early diagnostic biomarkers prognostic tools. We discuss weight loss effects diet-based interventions healthy lifestyles treatment patients, highlighting impact on restoration intestinal barrier structure. also describe encouraging preclinical findings modulation improve functions CLD, boost antitumor probiotic supplementations or anti-hypercholesterolemic drug treatment), ultimately delay HCC. The development safe effective strategies that target holds promise cancer prevention treatment, especially if personalized options will be considered.

Language: Английский

---

Interaction between the liver transcriptome and gut microbiota in mice during Toxoplasma gondii infection as identified by integrated transcriptomic and microbiome analysis

BMC Microbiology, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 14, 2025

Toxoplasma gondii is a single-cell parasite capable of infecting both humans and variety animal species. Although T. infection known to adversely affect the liver gut microbiota, precise interplay between microbiome transcriptome in infected mice remains largely unknown. In this study, we artificially induced acute chronic stages BALB/c via oral low doses (n = 10) PRU (Type II) bradyzoites. Then, performed fecal 16S rRNA gene amplicon sequencing RNA investigate composition microbiota expression profiles long non-coding RNAs (lncRNAs), circular (circRNAs), microRNAs (miRNAs), messenger (mRNAs) livers with at different infection. Analysis revealed dynamic alterations following over course cycle. Notably, observed significant increase abundance Enterobacteriaceae during stage infection, while Lactobacteriaceae was elevated stage. Liver analysis identified numerous differentially expressed (DE) mRNAs potentially involved mediating immune responses inflammation by gondii. During several pro-inflammatory genes, including Lpin1, Usp2, Pim3, Il6ra were significantly up-regulated liver. Among these, Lpin1 may be closely associated development overgrowth. Conversely, some anti-inflammatory such as Dmbt1, Ddit4, exclusively Gene ontology (GO) enrichment further stage-specific features functionality. Specifically, pathways enriched. Interestingly, related regulation, 'defense response Gram-negative bacterium', 'antimicrobial humoral mediated antimicrobial peptide', response' Additionally, competing endogenous (CeRNAs) networks that DElncRNAs DEcircRNAs competitively regulated DEmiRNA mmu-miR-690, which targets Nr1d1 gene. These findings provide insights into complex summary, our results highlight intricate interaction key genes

Language: Английский

---

Antibiotic-induced gut dysbiosis: unraveling the gut-heart axis and its impact on cardiovascular health

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 17, 2025

Language: Английский

---

The Role of the Gut–Biliary–Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(4), P. 124 - 124

Published: March 24, 2025

Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations gut microbiota, mutual implications on gut–liver axis gut–biliary permeability status, have been massively investigated proposed as pathogenetic deus ex machina. Results: HCC setting, elevated intestinal levels of Escherichia coli other Gram-negative bacteria demonstrated, resulting a close association increased lipopolysaccharide (LPS) serum and, consequently, chronic systemic inflammation. contrast, microbiota individuals feature reduced Lactobacillus spp., Bifidobacterium Enterococcus spp. CC evidence has revealed an expression enhanced Actynomices Alloscardovia Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty (SCFAs), oxidative-stress-derived products, configure network severely impacting progression HBLC. Conclusions: era Precision Medicine, clarification composition functioning settings can contribute to identification individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, prognostic/predictive tools.

Language: Английский

---

Optimizing Cancer Treatment Through Gut Microbiome Modulation

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1252 - 1252

Published: April 7, 2025

The gut microbiome plays a pivotal role in modulating cancer therapies, including immunotherapy and chemotherapy. Emerging evidence demonstrates its influence on treatment efficacy, immune response, resistance mechanisms. Specific microbial taxa enhance checkpoint inhibitor while dysbiosis can contribute to adverse outcomes. Chemotherapy effectiveness is also influenced by composition, with engineered probiotics prebiotics offering promising strategies drug delivery reduce toxicity. Moreover, metabolites, such as short-chain fatty acids, systems have shown potential improve therapeutic responses. These findings underscore the importance of personalized microbiome-based approaches optimizing treatments.

Language: Английский

---

New insights into biomarkers and risk stratification to predict hepatocellular cancer

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 23, 2025

Abstract Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide, with more than a doubling incidence over past two decades in United States. Yet, survival rate remains less 20%, often due to late diagnosis at advanced stages. Current HCC screening approaches are serum alpha-fetoprotein (AFP) testing and ultrasound (US) cirrhotic patients. However, these remain suboptimal, particularly setting underlying obesity metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH), which also rising incidence. Therefore, there an urgent need for novel biomarkers that can stratify risk predict early HCC, curable. Advances biology, multi-omics technologies, artificial intelligence, precision algorithms have facilitated development promising candidates, several emerging from completed phase 2 3 clinical trials. This review highlights performance mechanistic perspective provides new insight into how pathological processes be detected through blood-based biomarkers. Through human studies compiled animal models pathways such as TGF-β pathway, biological progression chronic disease cirrhosis delineated. integrated approach merit further validation refine improve detection stratification.

Language: Английский

---

Gut Microbiota and Hepatocellular Carcinoma: Metabolic Products and Immunotherapy Modulation

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(9)

Published: May 1, 2025

ABSTRACT Background The relationship between hepatocellular carcinoma (HCC) and gut microbiota has gained attention for its impact on HCC immunotherapy. Methods Key microbial metabolites, including bile acids, toll‐like receptor 4, short‐chain fatty bacterial toxins, contribute to progression influence immune responses through the gut‐liver axis. As checkpoint inhibitors (ICIs) become common in treatment, modulating offers new strategies enhance ICIs efficacy. However, individual differences composition introduce challenges, with some patients showing resistance ICIs. Results This review summarizes latest findings role of explores emerging therapeutic approaches, fecal transplantation, probiotics, antibiotics, natural compounds. Conclusions focus is translating these insights into personalized medicine optimize improve treatment outcomes.

Language: Английский

---