L-arginine metabolism as pivotal interface of mutual host–microbe interactions in the gut

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 26, 2023

L-arginine (L-arg) is a versatile amino acid and central intestinal metabolite in mammalian microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways the regulation cell division growth. It also serves source carbon, nitrogen, energy or substrate for protein synthesis. Consequently, can simultaneously modify immune functions, intraluminal metabolism, microbiota, pathogenesis. While dietary intake, turnover de novo synthesis usually supply sufficient amounts, expression several key enzymes metabolism change rapidly dramatically following inflammation, sepsis, injury. availability be restricted due to increased catabolism, transforming into an essential acid. Here, we review enzymatic cells their role function, colonization resistance, pathogenesis gut.

Language: Английский

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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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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Language: Английский

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From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3001 - 3001

Published: Feb. 3, 2023

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two many measures increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis multisystem inflammatory syndrome children (MIS-C). This paper integrates currently disparate innate hyperactivation relates these to SARS-CoV-2 activation immunity. Aggregated data include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat pyrin-domain-containing (NLRPs), retinoic acid-inducible gene I (RIG-I) melanoma-differentiation-associated 5 (MDA-5). mainly activates virus-associated TLR3, TLR7, TLR8, NLRP3, RIG-1 MDA-5. Severe COVID-19, however, is characterized by additional TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 NOD2, which primarily responsive bacterial antigens. The patterns Kawasaki disease, or MIS-C, mimic those rather than alone suggesting autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral known synergize produce required support disease pathology. Additional studies demonstrate anti-bacterial antibodies account for autoantigen targets complications.

Language: Английский

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Helicobacter pylori, Protected from Antibiotics and Stresses Inside Candida albicans Vacuoles, Cause Gastritis in Mice

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8568 - 8568

Published: Aug. 2, 2022

Due to (i) the simultaneous presence of

Language: Английский

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Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: June 17, 2022

Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), serum (1→3)-β-D-glucan (BG), from the to blood circulation (gut translocation) in dengue are still less studied. Perhaps, infection might induce pathogenic molecules that affect disease severity. At enrollment, there were 31 cases febrile critical phases at 4.1 ± 0.3 days 6.4 1.1 illness, respectively, with leaky as indicated by positive lactulose-to-mannitol excretion ratio. With bacteriome, patients phase (more severe dengue; n = 23) demonstrated more predominant abundance Bacteroidetes Escherichia spp. lower Bifidobacteria when compared healthy control (n 5). Meanwhile, most bacteriome results stage 8) comparable control, except for cases. Additionally, endotoxemia enrollment was five (62.5%) 19 (82.6%) phases, while BG detectable two (25%) 20 (87%) respectively. There higher peripheral non-classical monocytes natural killer cells (NK cells) phage than stage. Then, (CD14 - CD16 + ) NK (CD56 increased 4 7 illness stages, elevation LPS and/or day also associated increase monocytes, cells, cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria bacteriomes) along syndrome) be collaborated impaired microbial (lower causing infection.

Language: Английский

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Cyclic GMP–AMP Synthase (cGAS) Deletion Reduces Severity in Bilateral Nephrectomy Mice through Changes in Neutrophil Extracellular Traps and Mitochondrial Respiration

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1208 - 1208

Published: April 18, 2023

Uremia-induced systemic inflammation is partly caused by the dissemination of microbial molecules such as lipopolysaccharide and bacterial double-stranded DNA from leaked gut damaged immune cells in response to molecules. Cyclic GMP-AMP synthase (cGAS) can recognize fragmented induce cGAMP synthesis for activation stimulator interferon genes (STING) pathway. To study effect cGAS uremia-induced inflammation, we performed bilateral nephrectomy (BNx) wild-type knock-out mice found that leakage blood uremia both groups were similar. However, serum cytokines (TNF-α IL-6) neutrophil extracellular traps (NETs) decreased significantly cGAS-/- neutrophils after stimulation with LPS or cell-free DNA. Transcriptomic analysis LPS-stimulated also confirmed down-regulation effector functions. The flux showed exhibited a higher respiratory rate than despite having similar mitochondrial abundance function. Our results suggest may control functions respiration

Language: Английский

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Extracellular traps in peripheral blood mononuclear cell fraction in childhood-onset systemic lupus erythematosus

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 5, 2024

Although the role of low-density granulocytes (LDGs), neutrophils in peripheral blood mononuclear cell (PBMC) fraction, and neutrophil extracellular traps (NETs) assessing lupus disease severity is acknowledged, data specific to childhood-onset remains scarce. This study analyzed 46 patients with systemic erythematosus (82.6% females, mean age 14.5 ± 0.3 years), including 26 cases normal complement levels 20 low levels, along healthy adult volunteers. Key parameters that distinguished volunteers from differentiated between were serum interferon (IFN)-α, citrullinated histone 3 (CitH3), (ETs) LDGs. However, NETs (assessed by nuclear staining morphology), LDG abundance, other (such as endotoxemia, cytokines, double-stranded (ds) DNA) did not show such differentiation. When lipopolysaccharide (LPS) was administered LDGs PBMC it induced ETs both groups, indicating inducible nature ETs. In volunteers, activation recombinant IFN-α or dsDNA isolated (identified using immunofluorescent for CitH3, myeloperoxidase, elastase) at 45 min h post-stimulation, respectively. Additionally, approximately half underwent late apoptosis determined flow cytometry analysis. Activation also led a more pronounced expression CD66b, an adhesion molecule, compared regular-density neutrophils, suggesting higher activity conclusion, and/or may transform into before progressing NETosis apoptosis, potentially exacerbating through death-induced self-antigens. Therefore, could provide deeper insights pathophysiology lupus.

Language: Английский

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Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(15), P. 2283 - 2293

Published: April 14, 2023

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health event, resulting in significant social and economic burden. Although COVID-19 was initially characterized as an upper pulmonary infection, recent evidence suggests that it is complex including gastrointestinal symptoms, such diarrhea, nausea, vomiting. Moreover, remains unclear whether symptoms are direct infection of tract SARS-CoV-2 or result systemic immune activation subsequent dysregulation homeostatic mechanisms. This review provides brief overview mechanisms which disrupts integrity barrier mechanical barrier, chemical microbial barrier.

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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