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

---

Macrophage depletion alters bacterial gut microbiota partly through fungal overgrowth in feces that worsens cecal ligation and puncture sepsis mice

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 4, 2022

Abstract Because macrophage dysfunction from some emerging therapies might worsen gut-derived sepsis, cecal ligation and puncture (CLP) sepsis are performed in mice with clodronate-induced depletion. Macrophage depletion (non-sepsis) increased fecal Ascormycota, a subtle change bacterial microbiota, that possibly induced gut-barrier defect as Candida pintolopesii Enterococcus faecalis were identified blood. Sepsis macrophage-depleted was more severe than control indicated by mortality, cytokines, organ injury (liver, kidney, spleen), gut-leakage (FITC-dextran), Proteobacteria, blood organisms (bacteria fungi). Lysate of C. or purified (1 → 3)-β- d -glucan (BG; major component fungal cell wall) enhanced growth Klebsiella pneumoniae Escherichia coli isolated the CLP implying direct enhancer to species. Moreover, synergy LPS BG on enterocytes (Caco-2) (Transepithelial electrical resistance) neutrophils (cytokines) also supported an influence gut fungi worsening sepsis. In conclusion, through selectively facilitated bacteria (dysbiosis) worsened leading profound systemic responses against gut-translocated BG. Our data possible adverse effect severity spontaneous elevation fungi.

Language: Английский

---

Mitochondrial DNA Efflux Maintained in Gingival Fibroblasts of Patients with Periodontitis through ROS/mPTP Pathway

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 15

Published: June 8, 2022

Mitochondria have their own mitochondrial DNA (mtDNA). Aberrant mtDNA is associated with inflammatory diseases. believed to induce inflammation via the abnormal release. Periodontitis an infectious, oral disease. Human gingival fibroblasts (HGFs) from patients chronic periodontitis (CP) shown generate higher reactive oxygen species (ROS) that cause oxidative stress and decreased copy number. Firstly, cell-free was identified in plasma CP mice through qRT-PCR. Next, we investigated whether efflux maintained primary cultures of HGFs possible underlying mechanisms using adenovirus-mediated transduction live cell imaging qRT-PCR analysis. Here, reported increased mice. Additionally, confirmed had significant mitochondria compared healthy HGFs. Furthermore, lipopolysaccharide (LPS) Porphyromonas gingivalis can also release Mechanistically, LPS upregulated ROS levels permeability transition pore (mPTP) opening by inhibition pyruvate dehydrogenase kinase (PDK)2 expression, resulting Importantly, even persistent after removed cells were passaged next three generations, indicating abnormalities retained vitro, similar hosts. Taken together, our results elucidate ROS/mPTP activity. Therefore, work indicates may be a diagnostic therapeutic target for periodontitis.

Language: Английский

---

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Cells, Journal Year: 2022, Volume and Issue: 11(7), P. 1103 - 1103

Published: March 24, 2022

Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases-mild (upper respiratory tract symptoms without pneumonia; n = 27), moderate (pneumonia hypoxia; 28), severe with 20)-versus healthy control (n 15) were evaluated, together vitro experiments. Accordingly, counts, serum cytokines (IL-6 IL-8), lipopolysaccharide (LPS), bacteria-free DNA, NETs parameters (fluorescent-stained nuclear morphology, dsDNA, elastase, histone-DNA complex, myeloperoxidase-DNA complex) found differentiate severity, whereas (1→3)-β-D-glucan (BG) was different cases. Despite non-detectable DNA volunteers, using bacteriome analysis, proteobacterial similarly predominant both cases (all severities). In parallel, only from cases, but not mild activated NETs, as determined by supernatant Peptidyl Arginine Deiminase 4, morphology. With experiments, LPS plus BG (LPS + BG) more prominently induced cytokines, NFκB, reactive oxygen species, when compared activation each molecule alone. conclusion, pathogen molecules translocation along neutrophilia cytokinemia COVID-19-activated, NETs-induced hyperinflammation.

Language: Английский

---

The causality of gut microbiota on onset and progression of sepsis: a bi-directional Mendelian randomization analysis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Several observational studies have proposed a potential link between gut microbiota and the onset progression of sepsis. Nevertheless, causality sepsis remains debatable warrants more comprehensive exploration.

Language: Английский

---

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

---

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

---

Sepsis Encephalopathy Is Partly Mediated by miR370-3p-Induced Mitochondrial Injury but Attenuated by BAM15 in Cecal Ligation and Puncture Sepsis Male Mice

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5445 - 5445

Published: May 13, 2022

BAM15 (a mitochondrial uncoupling agent) was tested on cecal ligation and puncture (CLP) sepsis mice with in vitro experiments. attenuated as indicated by survival, organ histology (kidneys livers), spleen apoptosis (activated caspase 3), brain injury (SHIRPA score, serum s100β, miR370-3p, TNF-α, apoptosis), systemic inflammation (cytokines, cell-free DNA, endotoxemia, bacteremia), blood-brain barrier (BBB) damage (Evan's blue dye the presence of green fluorescent

Language: Английский

---

More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 4026 - 4026

Published: April 5, 2022

(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs reported to have various effects. Here, BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles many (1→6)-glycosidic bonds), Oat-BG (1→4)-linkages), were tested. In comparison dextran sulfate solution (DSS) alone in mice, DSS each these did not alter the weight loss, stool consistency, colon injury (histology cytokines), endotoxemia, serum BG, fecal microbiome but Pachyman-DSS-treated mice demonstrated highest cytokine elicitation (TNF-α IL-6). Likewise, a tail vein injection together intraperitoneal lipopolysaccharide (LPS) induced levels cytokines at 3 h post-injection than LPS or other BGs. With bone marrow-derived macrophages, BG only TNF-α (most prominent Pachyman), while additively increased several (TNF-α, IL-6, IL-10); inflammatory genes (iNOS, IL-1β, Syk, NF-κB); cell energy alterations (extracellular flux analysis). conclusion, proinflammatory synergistic effect on followed by WGP, possibly through Syk-associated interactions between Dectin-1 TLR-4 signal transduction pathways. Selection proper form for specific clinical conditions might be beneficial.

Language: Английский

---

Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Bio-Design and Manufacturing, Journal Year: 2022, Volume and Issue: 6(3), P. 255 - 267

Published: Dec. 28, 2022

Language: Английский

---