Gut bacterial extracellular vesicles: important players in regulating intestinal microenvironment

Liang, Xiao; Dai, Nini; Sheng, Kangliang; Lu, Hengqian; Wang, Jingmin; Chen, Liping; Wang, Yongzhong

doi:10.1080/19490976.2022.2134689

Cited by 52 publications

(29 citation statements)

References 167 publications

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“…In recent years, both our understanding of the gut microbiota and its complex relationship to disease have significantly increased. For instance, obesity contributes to altered intestinal microenvironments that support a greater variety of virus species than those found in hosts that are slimmer 32 . In this context, pathogenic mutations that can cause severe disease are more likely to be produced.…”

Section: Pathogenesis and Pathophysiology Of Obesitymentioning

confidence: 99%

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

Chen,

Wang,

Chen

et al. 2024

Pharmacology Res & Perspec

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Obesity is a major risk factor for morbidity and mortality because it has a close relationship to metabolic illnesses, such as diabetes, cardiovascular diseases, and some types of cancer. With no drugs available, the mainstay of obesity management remains lifestyle changes with exercise and dietary modifications. In light of the tremendous disease burden and unmet therapeutics, fresh perspectives on pathophysiology and drug discovery are needed. The development of epigenetics provides a compelling justification for how environmental, lifestyle, and other risk factors contribute to the pathogenesis of obesity. Furthermore, epigenetic dysregulations can be restored, and it has been reported that certain natural products obtained from plants, such as tea polyphenols, ellagic acid, urolithins, curcumin, genistein, isothiocyanates, and citrus isoflavonoids, were shown to inhibit weight gain. These substances have great antioxidant potential and are of great interest because they can also modify epigenetic mechanisms. Therefore, understanding epigenetic modifications to target the primary cause of obesity and the epigenetic mechanisms of anti‐obesity effects with certain phytochemicals can prove rational strategies to prevent the disease and develop novel therapeutic interventions. Thus, the current review aimed to summarize the epigenetic mechanisms and advances in therapies for obesity based on natural products to provide evidence for the development of several potential anti‐obesity drug targets.

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Section: Pathogenesis and Pathophysiology Of Obesitymentioning

confidence: 99%

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

Chen,

Wang,

Chen

et al. 2024

Pharmacology Res & Perspec

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“…Furthermore, to clarify the gut microbiota‐targeted mechanisms of miR‐29a, we explored the relationship between these gut bacteria and HFD‐induced inflammation and examined the expression of IL‐6 in the gut and liver. Previous studies have reported that the abundance of Parabacteroides , Bacteroides , and Mucispirillum is positively correlated with the blood levels of IL‐6 and LPS in chronic inflammation [ 70,71 ] and the brain cortex. [ 72 ] Together with our earlier report, [ 73 ] the present work confirmed that miR‐29a could modulate IL‐6 expression and reduce tissue inflammation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐29a Compromises Hepatic Adiposis and Gut Dysbiosis in High Fat Diet‐Fed Mice via Downregulating Inflammation

Yang

Huang

Wang

et al. 2023

Molecular Nutrition Food Res

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Scope: miR-29a expression patterns influence numerous physiological phenomena. Of note, upregulation of miR-29a ameliorates high-fat diet (HFD)-induced liver dysfunctions in mice. However, the miR-29a effect on gut microbiome composition and HFD-induced gut microbiota changes during metabolic disturbances remains unclear. The study provides compelling evidence for the protective role of miR-29a in gut barrier dysfunction and steatohepatitis. Methods and results: miR-29a overexpressed mice (miR-29aTg) are bred to characterize intestinal, serum biochemical, and fecal microbiota profiling features compared to wild-type mice (WT). Mice are fed an HFD for 8 months to induce steatohepatitis, and intestinal dysfunction is determined via histopathological analysis. miR-29aTg has better lipid metabolism capability that decreases total cholesterol and triglyceride levels in serum than WT of the same age. The study further demonstrates that miR-29aTg contributes to intestinal integrity by maintaining periodic acid Schiff positive cell numbers and diversity of fecal microorganisms. HFD-induced bacterial community disturbance and steatohepatitis result in more severe WT than miR-29aTg. Gut microorganism profiling reveals Lactobacillus, Ruminiclostridium_9, and Lachnoclostridium enrichment in miR-29aTg and significantly decreases interleukin-6 expression in the liver and intestinal tract. Conclusion: This study provides new evidence that sheds light on the host genetic background of miR-29a, which protects against steatohepatitis and other intestinal disorders.

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“…In order to achieve a precise modulation of gut microbiome with clinical effectiveness, it is essential to identify the regulatory mechanisms that control the host-microbiome interactions. Recently, microbiome-released extracellular vesicles (MEVs) have emerged as a key delivery mechanism in controlling intestinal microenvironment and bacteria-host communications 13,48 . MEVs are small membrane-bound phospholipid vesicles that encase a spectrum of biologically active molecules (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids) that protect them from lytic enzymes and RNases in the extracellular environment 49 and facilitate their horizontal transfer across both short and distant locations, such as the brain 50,51 .…”

Section: Discussionmentioning

confidence: 99%

“…have emerged as a key delivery mechanism in controlling intestinal microenvironment and bacteria-host communications 13,48 . MEVs are small membrane-bound phospholipid vesicles that encase a spectrum of biologically active molecules (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids) that protect them from lytic enzymes and RNases in the extracellular environment 49 and facilitate their horizontal transfer across both short and distant locations, such as the brain 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive multi-omics characterization of gut microbiome extracellular vesicles reveals a connection to gut-brain axis signaling

Sultan

Yousuf

Yeo

et al. 2022

Preprint

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Microbiota-gut-brain axis is an evident pathway of host-microbiota crosstalk that is linked to multiple brain disorders. Microbiota released extracellular vesicles (MEVs) has emerged as a key player in intercellular signaling in host microbiome communications. However, their role in gut-brain axis signaling is poorly investigated. Here, we performed a deep multi-omics profiling of MEVs content generated ex vivo and from stool samples in order to get some insights on their role in gut-brain-axis signaling. Metabolomics profiling identified a wide array of metabolites embedded in MEVs, including lipids, carbohydrates, amino acids, vitamins, and organic acids. Interestingly, many neurotransmitter-related compounds were detected inside MEVs, including arachidonyl-dopamine (NADA), gabapentin, glutamate and N-acylethanolamines. Next, we aimed to identify commensal microbes with psychobiotic activity. We isolated 58 Bacteroides strains assigned to four genera, 11 species, and 4 new species based on 16S rDNA sequencing. We performed whole genome sequencing of 18 representative isolates, followed by a comparative analysis of the structure of polysaccharide utilization loci (PUL) and glutamate decarboxylase (GAD), a genetic system involved in GABA production. Quantifying GABA was done using competitive ELISA, wherein three isolates (B. finegoldii, B. faecis, and B. caccae) showed high GABA production (4.5-7 mM range) in supernatant whereas 2.2 to 4 uM GABA concentration was detected inside microvesicles extracted using ultracentrifugation. To test the biodistribution of MEVs from the gut to other parts of the body, CACO-2, RIN-14 B, and hCMEC/D3 cells showed a capacity to internalize labeled MEVs through an endocytic mechanism. Additionally, MEVs exhibited a dose dependent paracellular transport through CACO-2 intestinal cells and hCMEC/D3 brain endothelial cells. In vivo results showed biodistribution of MEVs to liver, stomach and spleen. Overall, our results reveal the capabilities of MEVs to cross the intestinal and blood brain barriers to deliver their cargoes of neuroactive molecules to the brain as a new signaling mechanism in microbiota-gut-brain axis communications.

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Gut bacterial extracellular vesicles: important players in regulating intestinal microenvironment

Cited by 52 publications

References 167 publications

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

MicroRNA‐29a Compromises Hepatic Adiposis and Gut Dysbiosis in High Fat Diet‐Fed Mice via Downregulating Inflammation

Comprehensive multi-omics characterization of gut microbiome extracellular vesicles reveals a connection to gut-brain axis signaling

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