Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 13, 2023

Abstract In the past period, due to rapid development of next-generation sequencing technology, accumulating evidence has clarified complex role human microbiota in cancer and therapeutic response. More importantly, available seems indicate that modulating composition gut improve efficacy anti-cancer drugs may be feasible. However, intricate complexities exist, a deep comprehensive understanding how interacts with is critical realize its full potential treatment. The purpose this review summarize initial clues on molecular mechanisms regarding mutual effects between development, highlight relationship microbes immunotherapy, chemotherapy, radiation therapy surgery, which provide insights into formulation individualized strategies for management. addition, current emerging microbial interventions as well their clinical applications are summarized. Although many challenges remain now, great importance cannot overstated strategies, it necessary explore holistic approach incorporates modulation cancer.

Language: Английский

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The gut microbiota contributes to the development of Staphylococcus aureus-induced mastitis in mice

The ISME Journal, Journal Year: 2020, Volume and Issue: 14(7), P. 1897 - 1910

Published: April 27, 2020

Language: Английский

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Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice

World Journal of Hepatology, Journal Year: 2019, Volume and Issue: 11(8), P. 619 - 637

Published: Aug. 23, 2019

Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used alleviate NAFLD, successful treatment options are limited. One of main barriers finding safe effective drugs for long-term use NAFLD is fast initiation progression available preclinical models. Therefore, we need models that (1) mimic human manifestation (2) a longer time allow design superior treatments.To characterize model prolonged high-fat diet (HFD) feeding investigation NAFLD.In this study, utilized HFD examine features C57BL/6 male mice. We fed mice with (60% fat, 20% protein, carbohydrate) 80 wk promote obesity (Old-HFD group, n = 18). A low-fat (LFD) (14% 32% 54% was administered same duration age-matched (Old-LFD 15). An additional group maintained on LFD (Young-LFD, 20) shorter (6 wk) distinguish between age-dependent age-independent effects. Liver, colon, adipose tissue, feces were collected histological molecular assessments.Prolonged led insulin resistance. Histological analysis demonstrated steatosis, cell injury, portal lobular inflammation fibrosis. In addition, markers endoplasmic reticulum stress established tissue increased phosphorylated Jnk CHOP. Lastly, evaluated gut microbial composition Old-LFD Old-HFD. observed relative abundance Firmicutes phylum. At genus level, significant Adercreutzia, Coprococcus, Dorea, Ruminococcus decreased Turicibacter Anaeroplasma mice.Overall, these data suggest chronic consumption can pathophysiological some events patients.

Language: Английский

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Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis

Gut, Journal Year: 2019, Volume and Issue: 68(8), P. 1477 - 1492

Published: March 14, 2019

There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated role of gut-liver crosstalk murine Mdr2 knockout (Mdr2-/-) model resembling primary sclerosing cholangitis (PSC).Male Mdr2-/-, Mdr2-/- crossed with hepatocyte-specific deletion caspase-8 (Mdr2-/- /Casp8∆hepa) wild-type (WT) control mice were housed 8 or 52 weeks, respectively, to characterise impact on gut including bile acid profiling. To block caspase activation, pan-caspase inhibitor (IDN-7314) was administered. Finally, -associated dysbiosis studied by transfer experiments.Mdr2-/- displayed an unfavourable signature pronounced NLRP3 inflammasome activation within axis. Intestinal prompted barrier dysfunction increased bacterial translocation amplifying hepatic NLRP3-mediated response. Transfer into healthy WT induced significant injury recipient mice, highlighting causal progression. Strikingly, IDN-7314 dampened ameliorated injury, reversed serum profile cholestasis-associated signature.MDR2-associated cholestasis triggers dysbiosis. In turn, endotoxin portal vein subsequent contribute higher injury. This process does not essentially depend hepatocytes, but can be blocked IDN-7314.

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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