Causal effects of gut microbiota on sepsis and sepsis-related death: insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 2, 2024

Abstract Background Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship underlying mechanisms remain unclear. Methods We evaluated association between gut composition using two-sample Mendelian randomization (MR) analysis based on published genome-wide study (GWAS) summary statistics. Sensitivity analyses were conducted to validate robustness of results. Reverse MR integration GWAS expression quantitative trait loci (eQTL) data performed identify potential genes therapeutic targets. Results Our identified 11 bacterial taxa associated with sepsis, increased abundance six showing positive relationships. Ten had effects 28-day survival outcome septic patients, associations. confirmed these did not provide evidence reverse causality. Integration eQTL revealed 76 passing data-based (SMR) test. Differential was observed patients healthy individuals. These represent targets for sepsis. Molecular docking predicted drug-target interactions, further supporting their potential. Conclusion provides insights development personalized treatment strategies offers preliminary candidate drugs future drug development.

Language: Английский

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Unpacking the sepsis controversy

Trauma Surgery & Acute Care Open, Journal Year: 2025, Volume and Issue: 10(1), P. e001733 - e001733

Published: March 1, 2025

Despite its many definitions and revisions, consensus statements clinical guidelines, the term 'sepsis' continues to be referred as a discrete entity that is often claimed direct cause of mortality. The assertion sepsis can defined 'life-threatening organ dysfunction caused by dysregulated host response infection,' has led field dominated failed trials informed host-centered, pathogen-agnostic, animal experiments in which models do not recapitulate condition. observations from National Health Service England claim 77.5% deaths occur those aged 75 years or older USA indicating most patients dying have also been diagnosed with 'hospice qualifying conditions,' seem refute by, rather than associated with, 'dysregulated response.' This piece challenges current conceptual framework forms basis definition. Here we posit result both definition use inappropriate models, ineffective treatments continue pursued this field.

Language: Английский

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Impact of Dietary Fiber on Inflammation and Insulin Resistance in Older Patients: A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2365 - 2365

Published: May 18, 2023

The beneficial impact of dietary fiber on the prevention and management several chronic conditions associated with aging, including diabetes, neurodegenerative, cardiovascular diseases, cancer, is well-known. High intake has been reduced inflammatory mediators counteracting low-grade inflammation typical older age. In addition, improves postprandial glucose response insulin resistance. contrast, during acute its effects resistance modulation immune are unclear. aim this narrative to summarize evidence for potential in adults, a particular focus those acutely ill. Available suggests that counteract improve metabolic health. gut microbiota composition may contribute improved function, particularly setting aging-associated dysbiosis. This phenomenon relevant implications ill, whom dysbiosis can be exacerbated. Our review leads conclusion interventions based manipulation could exploit resistance, if conducted from precision nutrition perspective. also true ill patient, even though strong lacking.

Language: Английский

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Practical Lessons on Antimicrobial Therapy for Critically Ill Patients

Antibiotics, Journal Year: 2024, Volume and Issue: 13(2), P. 162 - 162

Published: Feb. 6, 2024

Sepsis stands as a formidable global health challenge, with persistently elevated mortality rates in recent decades. Each year, sepsis not only contributes to heightened morbidity but also imposes substantial healthcare costs on survivors. This narrative review aims highlight the targeted measures that can be instituted alleviate incidence and impact of intensive care. Here we discuss reduce nosocomial infections prevention equipment patient colonisation by resilient pathogens. The overarching crisis bacterial resistance newly developed antimicrobial agents intensifies imperative for stewardship de-escalation. urgency has been accentuated years, notably during COVID-19 pandemic, high-dose steroids opportunistic presented escalating challenges. Ongoing research into airway colonisation’s role influencing disease outcomes among critically ill patients underscores importance tailoring treatments endotypes within heterogeneous populations, which are important lessons intensivists training. Looking ahead, significance novel delivery systems drug monitoring is poised increase. delves multifaceted barriers facilitators inherent effectively treating vulnerable infections. future trajectory care medicine hinges meticulous implementation vigilant programs, robust infection control measures, continued exploration innovative efficient technological solutions this demanding landscape.

Language: Английский

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The Interplay between Antibiotics and the Host Immune Response in Sepsis: From Basic Mechanisms to Clinical Considerations: A Comprehensive Narrative Review

Antibiotics, Journal Year: 2024, Volume and Issue: 13(5), P. 406 - 406

Published: April 28, 2024

Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and system, aiming clarify involved mechanisms their clinical impacts. From pre-clinical studies, exhibit various immunomodulatory effects, including regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation P38/Pmk-1 Pathway, inhibition Matrix Metalloproteinases, blockade nitric oxide synthase, caspase-induced apoptosis. Additionally, antibiotic-induced alterations microbiome are associated changes in systemic immunity, affecting cellular humoral responses. The adjunctive use sepsis patients, particularly macrolides, has attracted attention immune-regulatory effects. However, there limited data comparing different types macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially severe cases hyper-inflammatory response. While septic shock have shown mixed results regarding mortality rates response modulation, conflicting findings also observed macrolides acute respiratory distress syndrome. In conclusion, is pressing need tailor antibiotic therapy based patient’s profile optimize outcomes management.

Language: Английский

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Sepsis‑induced cardiac dysfunction and pathogenetic mechanisms (Review)

Molecular Medicine Reports, Journal Year: 2023, Volume and Issue: 28(6)

Published: Oct. 17, 2023

Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead multi‑organ failure. Health care advances have improved outcomes in critical illness, but it still remains leading cause death. Septic cardiomyopathy heart dysfunction brought on by sepsis. common consequence sepsis has mortality rate up 70%. There lack understanding septic pathogenesis; knowledge its pathogenesis identification potential therapeutic targets reduce patients with clinical improvements. The present review aimed summarize cardiac sepsis, focus mitochondrial dysfunction, metabolic changes cell death modalities pathways. summarized diagnostic criteria outlook for treatment, goal identifying appropriate treatment methods this disease.

Language: Английский

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Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

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

Published: Jan. 31, 2024

Background It is unclear what the causal relationship between gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a link exists two. Methods This study used publicly available genome-wide association studies (GWAS) summary data of microbiota, sepsis, sepsis (critical care), (28-day death in critical care) perform two-sample MR analysis. To ensure robustness results, also conducted sensitivity Results For susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78–0.94, p 0.0017) was protective against while Lentisphaerae 0.89, 0.80–0.99), Gammaproteobacteria 1.37, 1.08–1.73), Clostridiaceae1 1.21, 1.04–1.40), RuminococcaceaeUCG011 1.10, 1.01–1.20), Dialister 0.85, 0.74–0.97), Coprococcus2 0.81, 0.69–0.94) presented suggestive with development (all < 0.05). IVW indicated 0.70, 0.53–0.93), 0.67, 0.50–0.91), Anaerostipes 0.49, 0.31–0.76), LachnospiraceaeUCG004 0.51, 0.34–0.77), Coprococcus1 0.66, 0.44–0.99) showed negative correlation suggested four bacterial taxa had normally significant risk sepsis-related death, including 0.54, 0.30–0.95), 0.34, 0.14–0.83), Ruminiclostridium6 0.43, 0.22–0.83), 0.45, 0.21–0.97), two were significantly positively linked namely, Mollicutes 2.03, 1.01–4.08) Bacteroidales 2.65, 1.18–5.96) The above correlations verified by additional analyses. Conclusion research found several causally care, 28-day mortality care.

Language: Английский

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Sex differences and individual variability in the captive Jamaican fruit bat (Artibeus jamaicensis) intestinal microbiome and metabolome

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

Published: Feb. 9, 2024

Abstract The intestinal microbiome plays an important role in mammalian health, disease, and immune function. In light of this function, recent studies have aimed to characterize the microbiomes various bat species, which are noteworthy for their roles as reservoir hosts several viruses known be highly pathogenic other mammals. Despite ongoing research, its function especially effects changes on host remains nebulous. Here, we describe a novel methodology investigate captive Jamaican fruit bats ( Artibeus jamaicensis ). We observed high degree individual variation addition sex- cohort-linked differences. was correlated with metabolite composition, possibly contributing differences status. This work provides basis future infection field examine detail antiviral immunity.

Language: Английский

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Functional connectivity within sensorimotor cortical and striatal regions is regulated by sepsis in a sex-dependent manner

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 120995 - 120995

Published: Jan. 1, 2025

Sepsis is a state of systemic immune dysregulation and organ failure that frequently associated with severe brain disability. Epidemiological studies have indicated younger females better prognosis clinical outcomes relative to males, though the sex-dependent response sepsis during post-sepsis recovery remains largely uncharacterized. Using modified polymicrobial intra-abdominal murine model surgical sepsis, we characterized acute effects on peripheral inflammation, inflammation functional connectivity in young adult mice both sexes. Following male female survived procedure, regained body weight within 7 days showed reduced diversity their gut microbiome. Interestingly, compared sepsis-induced changes observed mice, post-septic exhibited comparatively robust profile splenic cell expansion intracerebral glial proliferation healthy counterparts. Analysis resting-state Magnetic Resonance Imaging (fMRI) data collected from revealed while somatosensory cortex were affected equally sexes, intra-network strength striatum preferentially increased males but remained near baseline mice. Additionally, network alterations projections periaqueductal gray superior colliculus as also between anterior cingulate striatum. Coupled sustained gliosis response, intra-striatal fMRI patterns could signify delayed sepsis. Together, our study provides evidence influences immunity, immunity manner, strongly indicating cognitive benefits recovering

Language: Английский

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Effects of probiotic treatment on the prognosis of patients with sepsis: a systematic review

World Journal of Emergency Medicine, Journal Year: 2025, Volume and Issue: 16(1), P. 18 - 18

Published: Jan. 1, 2025

Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that beneficial the host may benefit sepsis outcomes, but their effects still inconclusive. This study aimed evaluate overall effect of probiotics on prognosis patients with sepsis. We searched several sources for published/presented studies, including PubMed, EMBASE, Web Science, Cochrane Library US National Medicine Clinical Trials Register (www.clinicaltrials.gov) updated through July 30, 2023, identify all relevant randomized controlled trials (RCTs) or observational studies assessed effectiveness synbiotics in reported mortality. focused primarily mortality during period analyzed secondary 28-day mortality, in-intensive care unit (ICU) other outcomes. Data from 405 five RCTs 108 one cohort were included analysis. The quality was satisfactory, clinical heterogeneity existed. All adult tendency reduce sepsis, most decreasing trend incidence infectious complications, length ICU stay duration antibiotic use. There only RCT involving children. show promise improving reducing particularly patients. Despite limited number especially children, these findings will be encouraging practice treatment suggest gut microbiota-targeted therapy improve

Language: Английский

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