Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy

Gut, Journal Year: 2021, Volume and Issue: 71(4), P. 734 - 745

Published: May 18, 2021

Objective Programmed death 1 and its ligand (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in sensitisation Panax ginseng has been shown possess immunomodulatory potential. In this study, we aimed investigate whether combination treatment of polysaccharides (GPs) αPD-1 monoclonal antibody (mAb) could sensitise by modulating gut microbiota. Design Syngeneic mouse models were administered GPs mAb, sensitising antitumour effects therapy on assessed faecal transplantation (FMT) 16S PacBio single-molecule real-time (SMRT) sequencing. To assess immune-related metabolites, metabolomics analysis plasma samples was performed. Results We found increased mAb increasing microbial metabolites valeric acid decreasing L-kynurenine, as well ratio Kyn/Trp, which contributed suppression regulatory T cells induction eff after treatment. Besides, indicated that abundance Parabacteroides distasonis Bacteroides vulgatus higher responders anti-PD-1 blockade than non-responders clinic. Furthermore, sensitised PD-1 inhibitor mice receiving microbes FMT from six reshaping towards responders. Conclusion Our results demonstrate combined with may new strategy non-small cell patients immunotherapy. The can used novel biomarker predict

Language: Английский

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Metabolism and Metabolic Disorders and the Microbiome: The Intestinal Microbiota Associated With Obesity, Lipid Metabolism, and Metabolic Health—Pathophysiology and Therapeutic Strategies

Gastroenterology, Journal Year: 2020, Volume and Issue: 160(2), P. 573 - 599

Published: Nov. 27, 2020

Language: Английский

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Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

Adipocyte, Journal Year: 2021, Volume and Issue: 10(1), P. 48 - 65

Published: Jan. 1, 2021

Mammalian adipose tissue can be divided into two major types, namely, white (WAT) and brown (BAT). According to classical view, the main function of WAT is store excess energy in form triglycerides, while BAT a thermogenic that acts pivotal part maintaining core body temperature. White adipocytes display high plasticity transdifferentiate beige which have many similar morphological functional properties with under stimulations exercise, cold exposure other factors. This phenomenon also known as 'browning WAT'. In addition transdifferentiation, come from de novo differentiation tissue-resident progenitors. Activating inducing browning accelerate intake glycolipids reduce insulin secretion requirement, may new strategy improve metabolism resistance obese type 2 diabetes mellitus (T2DM) patients. review mainly discusses significance tissues treatment obesity T2DM, focuses on effect agent provides brand-new theoretical reference for prevention T2DM.

Language: Английский

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New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(11), P. 4011 - 4039

Published: Aug. 27, 2022

Language: Английский

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Obesity and insulin resistance: Pathophysiology and treatment

Drug Discovery Today, Journal Year: 2021, Volume and Issue: 27(3), P. 822 - 830

Published: Nov. 9, 2021

Language: Английский

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An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 11, 2023

Overweight and obesity have become a world-wide problem. However, effective intervention approaches are limited. Brown adipose tissue, which helps maintain body temperature contributes to thermogenesis, is dependent on uncoupling protein1. Over the last decade, an in-creasing number of studies found that activating brown tissue browning white can protect against obesity-related metabolic disease. has gradually appealing therapeutic target for prevention re-versal obesity. some important issues remain unresolved. It not certain whether increasing activity cause or effect weight loss what risks might be sympathetic nervous system-dependent non-shivering thermogenesis. In this review, we comprehensively summarize and/or such as cold exposure, exercise, small-molecule treatment. We highlight functional mechanisms treatment transplantation using batokine, system gut microbiome. Finally, discuss causality between induced by bariatric surgery, activity.

Language: Английский

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Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity

Theranostics, Journal Year: 2020, Volume and Issue: 10(24), P. 11302 - 11323

Published: Jan. 1, 2020

Background: Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during treatment obesity. The endogenous mechanism promoting thermogenesis or browning has indicated that gut microbiota is crucial regulator host balance. However, whether effects therapeutic intervention-induced modulation on adipocyte involved regulation leptin remains unclear. Method: adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy H&E staining. gene protein expression tissue detected qRT-PCR, immunoblotting, immunohistochemistry immunofluorescence microbiome signature was identified 16S rRNA amplicon sequencing, both mice with high-fat diet-induced obesity (DIO) antibiotics-induced depletion subjected to fecal transplantation. Results: Treatment Panax notoginseng saponins (PNS) shaped murine abundances Akkermansia muciniphila Parabacteroides distasonis, as result, DIO harbored distal significantly increased capacity reduce adiposity. PNS-induced could increase (BAT) beige reconstruction activating leptin-AMPK/STAT3 signaling pathway, which results promotion expenditure. Leptin an essential influence anti-obesity PNS. In cases deficiency, exerts negative (WAT), indicates PNS fail gene-deficient mice. exerted minimal effect antibiotic-induced depletion, confirmed correlation between altered remodeling tissues direct via AMPKα/STAT3 pathway C3H101/2 cells supported our vivo signalling through induced PNS-modulated reconstruction. Conclusion: Our revealed critical alterations microbiota-fat crosstalk provide avenues intervention

Language: Английский

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Role of gut microbiota in identification of novel TCM-derived active metabolites

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(5), P. 394 - 410

Published: Sept. 15, 2020

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing a lack formal scientific validation, the absence information regarding mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by host, but rather enter intestine be transformed gut microbiota. The microbiota is microbial community living animal intestines, and functions maintain host homeostasis health. Increasing evidences indicate that herbs closely affect composition, which associated with conversion components into active metabolites. These may significantly therapeutic activity TCMs. Microbiota analyses, conjunction modern multiomics platforms, can together identify novel functional metabolites form basis future research.

Language: Английский

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A review of saponin intervention in metabolic syndrome suggests further study on intestinal microbiota

Pharmacological Research, Journal Year: 2020, Volume and Issue: 160, P. 105088 - 105088

Published: July 16, 2020

Language: Английский

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Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet

Food Research International, Journal Year: 2020, Volume and Issue: 139, P. 109956 - 109956

Published: Dec. 8, 2020

Language: Английский

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