The leaky gut and the gut microbiome in sepsis – targets in research and treatment

Clinical Science, Journal Year: 2023, Volume and Issue: 137(8), P. 645 - 662

Published: April 1, 2023

Abstract Both a leaky gut (a barrier defect of the intestinal surface) and dysbiosis change in microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, worsen The syndrome refers status with which there is an increased permeability allowing translocation molecules from into blood circulation. It not just symptom gastrointestinal involvement, but also underlying that develops independently, its presence could be recognized by detection, blood, lipopolysaccharides (1→3)-β-D-glucan (major components microbiota). Gut-dysbiosis consequence reduction some bacterial species microbiome, as mucosal immunity defect, caused hypoperfusion, immune cell apoptosis, variety enteric neuro-humoral-immunity responses. A bacteria produce short-chain fatty acids barriers, leading pathogen molecules, circulation where it causes systemic inflammation. Even fungi might human patients sepsis, even though this has been consistently observed murine models probably because longer duration antibiotic use patients. virobiome partly consists bacteriophages detectable contents different between normal hosts. These alterations altogether interesting target for adjuvant therapies, e.g., faecal transplantation or probiotic therapy. Here, current information on along potential biomarkers, new treatment strategies, future research topics mentioned.

Language: Английский

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Probiotics as functional foods: How probiotics can alleviate the symptoms of neurological disabilities

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114816 - 114816

Published: May 8, 2023

Neurological disorders are diseases of the central nervous system with progressive loss tissue. One most difficult problems associated neurological is that there no clear treatment for these diseases. In this review, physiopathology some neurodegenerative diseases, etiological causes, drugs used and their side effects, finally role probiotics in controlling symptoms presented. Recently, researchers have focused more on microbiome gut-brain axis, which may play a critical maintaining brain health. Probiotics among important bacteria positive effects balance homeostasis via influencing microbiome. Other functions alleviating include anti-inflammatory properties, short-chain fatty acid production, production various neurotransmitters. The control abnormalities seen led to being referred as "psychobiotic. Given axis imbalance gut etiology disorders, could be considered safe agents positively affect complementary options disorders.

Language: Английский

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NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota

Nutrients, Journal Year: 2023, Volume and Issue: 15(13), P. 2992 - 2992

Published: June 30, 2023

The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as cofactor many cellular reactions well coenzyme different NAD+-consuming enzymes involved in the physiological homeostasis organs and systems. In mammals, synthesized from tryptophan or other vitamin B3 intermediates that precursors. Recent research suggests precursors play crucial role maintaining integrity gut barrier. Indeed, its deficiency has been associated with enhanced inflammation leakage, dysbiosis. Conversely, NAD+-increasing therapies confer protection against intestinal experimental conditions human patients, accumulating evidence indicating such favorable effects could be, at least part, mediated by concomitant changes composition microbiota. However, mechanisms which NAD+-based treatments affect microbiota are still poorly understood. this context, we have focused specifically on impact dysbiosis animal models. We further explored relationship between improved host metabolism immunity vivo. Overall, comprehensive review aims to provide new perspective effect strategies physiology.

Language: Английский

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Lupus exacerbation in ovalbumin-induced asthma in Fc gamma receptor IIb deficient mice, partly due to hyperfunction of dendritic cells

Asian Pacific Journal of Allergy and Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Background: Although allergy might be another factor that exacerbates lupus as demonstrated by several epidemiologic studies, the direct correlation between activities and is still in question. Objective:To explore allergic reaction activities. Methods:The asthma model using ovalbumin (OVA) administration wildtype (WT) Fc gamma receptor IIb deficient (FcgRIIb-/-) mice (a lupus-prone model) together with vitro experiments on bone marrow-derived dendritic cells (DCs) were performed.Results: At 2-weeks-post OVA, both WT FcgRIIb-/-mice similar indicated an elevation of IgE IL-4 serum asthma-liked lung histology (lung weight, inflammatory score, bronchial thickness) increased spleen weight.Apoptosis lungs spleens (activated caspase 3 immunohistochemistry) was detected only OVA-administered FcgRIIb-/-mice.Surprisingly, FcgRIIb-/-mice, active nephritis, anti-dsDNA, proteinuria, renal immune complex deposition (immunohistochemistry analysis) implying impact activities.Meanwhile, creatinine gut permeability defect (FitC-dextran assay endotoxemia) not different OVA versus control.In parallel, FcgRIIb-/-DCs more susceptible to activations lipopolysaccharide (LPS) than DCs CD80 major histocompatibility II (MHC II) flow cytometry analysis.Conclusions: OVA-induced exacerbated activity, possibly due hyper-responsiveness over from loss inhibitory FcgRIIb.The proper control beneficial for lupus.

Language: Английский

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Metagenomic symphony of the intestinal ecosystem: How the composition affects the mind

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 18, 2023

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and characterized by the damage to multiple target organs. The pathogenesis SLE complex, its etiology mainly involves genetic environmental factors. At present, there still lack effective means cure SLE. In recent years, growing evidence has shown gut microbiota, as an factor, triggers autoimmunity through potential mechanisms including translocation molecular mimicry, leads immune dysregulation, contributes development Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation other ways modulate microbiota appear be treatment for this review, dysbiosis in SLE, linking dysregulation associated with are summarized.

Language: Английский

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miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

United European Gastroenterology Journal, Journal Year: 2023, Volume and Issue: 11(8), P. 750 - 766

Published: Sept. 18, 2023

Abstract Background/Aim Diabetes has substantive co‐occurrence with disorders of gut‐brain interactions (DGBIs). The pathophysiological and molecular mechanisms linking diabetes DGBIs are unclear. MicroRNAs (miRNAs) key regulators gut dysmotility. We investigated whether impaired barrier function is regulated by a miRNA, miR‐10b‐5p, Methods created new mouse line using the Mb3Cas12a/Mb3Cpf1 endonuclease to delete mir‐10b globally. Loss studies in knockout (KO) mice were conducted characterize diabetes, dysmotility, dysfunction phenotypes these mice. Gain injecting KO miR‐10b‐5p mimic. Further, we performed miRNA‐sequencing analysis from colonic mucosa KO, wild type, mimic injected confirm (1) deficiency mice, (2) restoration after injection. Results Congenital loss led development hyperglycemia, dysfunction. Gut permeability was increased, but expression tight junction protein Zonula occludens‐1 reduced colon Patients or constipation‐ predominant irritable bowel syndrome, known DGBI that linked leaky gut, had significantly expression. Injection rescued alterations phenotypes. Conclusions Our study uncovered potential pathophysiologic mechanism links both dysmotility lacking miR‐10b‐5p. Treatment reversed diabetic, phenotypes, highlighting translational

Language: Английский

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Syk inhibitor attenuates lupus in FcγRIIb−/− mice through the Inhibition of DNA extracellular traps from macrophages and neutrophils via p38MAPK-dependent pathway

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 17, 2025

Abstract Spleen tyrosine kinase (Syk), an important hub of immune signaling, is activated by several signalings in active lupus which could be interfered Syk inhibitor but still not completely evaluated innate cells associated with activity. Hence, a (fostamatinib; R788) was tested vivo using Fc gamma receptor-deficient (FcγRIIb −/− ) mice and vitro (macrophages neutrophils). After 4 weeks oral inhibitor, 40 week-old FcγRIIb (a full-blown model) demonstrated less prominent parameters (serum anti-dsDNA, proteinuria, glomerulonephritis), systemic inflammation, as serum TNFa, IL-6, citrullinated histone H3 (CitH3), gut permeability defect, indicated FITC dextran assay, lipopolysaccharide (LPS), (1 → 3)-β-D-glucan (BG), extracellular traps (ETs) complex deposition spleens kidneys (immunofluorescent staining CitH3 immunoglobulin G) than placebo. Due to the spontaneous elevation LPS BG serum, plus (LPS + BG) used activate macrophages neutrophils. stimulation, neutrophils predominant abundance phosphorylated (Western blotting), pro-inflammatory responses (CD86 flow cytometry analysis, supernatant cytokines, ETs immunofluorescent, cytometry-based apoptosis). With RNA sequencing analysis western blotting, Syk-p38MAPK-dependent pathway suggested downregulating inflammatory pathways BG-activated Although both inhibitors against p38MAPK attenuated macrophage neutrophil WGP, apoptosis inhibition observed. These results that (fostamatinib) improved severity caused defect partly through Syk-p38MAPK anti-inflammation inhibited ET formation cytokine production from cells.

Language: Английский

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The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Neutrophil extracellular traps (NETs) are unique fibrous structures released by neutrophils in response to various pathogens, exhibiting both anti-inflammatory and proinflammatory effects. In autoimmune conditions, NETs serve as crucial self-antigens triggering inflammatory cascades activating the inflammasome complement systems, disrupting self-tolerance mechanisms accelerating responses. Furthermore, play a pivotal role modulating immune cell activation, affecting adaptive This review outlines intricate relationship between diseases, including arthritis, systemic Behçet's disease, lupus erythematosus, kidney skin sclerosis, vasculitis, gouty arthritis. It highlights potential of targeting therapeutic strategy diseases. By examining dynamic balance NET formation clearance this offers critical insights theoretical foundation for future research on NET-related mechanisms. Advances systems biology, flow cytometry, single-cell multiomics sequencing have provided valuable tools exploring molecular NETs. These advancements renewed focus offering promising avenues further investigation into their clinical implications.

Language: Английский

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Intratracheal Candida administration induced lung dysbiosis, activated neutrophils, and worsened lung hemorrhage in pristane-induced lupus mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 21, 2025

Because the innate immunity might and fungi in lungs enhance severity of lupus-induced diffuse alveolar hemorrhage (DAH), intraperitoneal pristane injection was performed C57BL6 mice with intratracheal administration by Candida albicans or phosphate buffer solution (PBS). Despite similar pristane-induced lupus (proteinuria, serum creatinine, anti-dsDNA) at 5 weeks model, worsened several characteristics, including mortality, body weight, cytokines (TNF-α IL-6), lung score, tissue (TNF-α, IL-6, IL-10), but not gut permeability (FITC-dextran assay), IL-10, immune cells spleens (flow cytometry analysis), activities peritoneal macrophages (polymerase-chain reaction). Although reduced proteobacterial abundance altered alpha beta diversity compared PBS control, microbiota different between pristane- non-pristane-administered mice. prominent Gram-negative bacteria role neutrophils DAH, lipopolysaccharide (LPS) without heat-killed preparation tested. Indeed, LPS induced more severe pro-inflammatory than stimulation alone as indicated expression genes IL-1β, Dectin-1, NF-κB). In conclusion, partly through enhanced neutrophil responses against fungi. More studies on colonization sputum from patients DAH are interesting.

Language: Английский

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