Effect of gut microbiome-derived metabolites and extracellular vesicles on hepatocyte functions in a gut-liver axis chip

Kang, Seong Goo; Choi, Yoon Young; Mo, Sung Jun; Kim, Tae Hyeon; Ha, Jang Ho; Hong, Dong Ho; Lee, Hayera; Park, Soo Dong; Shim, Jae-Jung; Lee, Jung-Lyoul; Chung, Bong Geun

doi:10.1186/s40580-022-00350-6

Cited by 11 publications

(3 citation statements)

References 51 publications

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“…Via microbial EVs, the biomolecules within the microbiota are transferred to other tissues, organs, or cells of the host to modulate the synthesis and secretion of proteins, nucleic acids, lipids, or other metabolites in the recipient cells. However, the impacts of different strains of microbiota on the host exhibit some degrees of uncertainty and diversity [ 105 ]. Some bacteria-derived EVs contain proteins capable of modulating the host immune system, but the content of these substances is contingent upon the classification and specific characteristics of the parent species [ 74 ].…”

Section: Microbiome–gut–brain Axismentioning

confidence: 99%

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond

Wang,

Luo,

Wang

et al. 2024

IJMS

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The intestinal ecological environment plays a crucial role in nutrient absorption and overall well-being. In recent years, research has focused on the effects of extracellular vesicles (EVs) in both physiological and pathological conditions of the intestine. The intestine does not only consume EVs from exogenous foods, but also those from other endogenous tissues and cells, and even from the gut microbiota. The alteration of conditions in the intestine and the intestinal microbiota subsequently gives rise to changes in other organs and systems, including the central nervous system (CNS), namely the microbiome–gut–brain axis, which also exhibits a significant involvement of EVs. This review first gives an overview of the generation and isolation techniques of EVs, and then mainly focuses on elucidating the functions of EVs derived from various origins on the intestine and the intestinal microenvironment, as well as the impacts of an altered intestinal microenvironment on other physiological systems. Lastly, we discuss the role of microbial and cellular EVs in the microbiome–gut–brain axis. This review enhances the understanding of the specific roles of EVs in the gut microenvironment and the central nervous system, thereby promoting more effective treatment strategies for certain associated diseases.

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Section: Microbiome–gut–brain Axismentioning

confidence: 99%

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond

Wang,

Luo,

Wang

et al. 2024

IJMS

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“…Its two chambers are separated by a porous membrane to let the hepatocytes in but inhibit microorganisms entering the chamber. 373 Nano-poly-boronic acid regulates sugar intake and liver lipogenesis, and finally prevents fructose and glucose absorption in the gut. 374 In addition, certain microorganisms' components are prepared into nanotechnology like light-sensitive Lactococcus lactis which is an oral live biotherapeutic agent that makes communication from the gut to the host more manageable.…”

Section: Mechanisms Linking the Liver-brain Axismentioning

confidence: 99%

Gut liver brain axis in diseases: the implications for therapeutic interventions

Yan,

Man,

Sun

et al. 2023

Sig Transduct Target Ther

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Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

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“…Moreover, seminal studies have demonstrated the crucial role of gut microbiome in influencing several disease conditions (Bull & Plummer, 2014; Clemente et al., 2012; de Vos et al., 2022; Hou et al., 2022; Li et al., 2008; Vijay & Valdes, 2022). The imbalance of the gut microbiota, referred to as gut dysbiosis, has been associated with biological effects in distant organs, leading to the identification of microbiota‐gut‐brain, microbiota‐gut‐lung, microbiota‐gut‐liver and microbiota‐gut‐skin axes (Giridharan et al., 2022; Kang et al., 2023; Varela‐Trinidad et al., 2022). These gut‐organ axes are bi‐ or multi‐directional, or multi‐channel communications that allow the gut and extra‐intestinal organs to communicate with one another and dictate the effect of the gut microbiome on human health.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of LPS+ bacterial extracellular vesicles along the gut‐hepatic portal vein‐liver axis

Jain,

Kumar,

Almousa

et al. 2024

J of Extracellular Vesicle

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Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter‐kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet‐induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage‐specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation‐related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well‐established biological effects induced by gut bacteria on distant organs.

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Effect of gut microbiome-derived metabolites and extracellular vesicles on hepatocyte functions in a gut-liver axis chip

Cited by 11 publications

References 51 publications

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond

Gut liver brain axis in diseases: the implications for therapeutic interventions

Characterisation of LPS+ bacterial extracellular vesicles along the gut‐hepatic portal vein‐liver axis

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