Daily Sepsis Research Analysis
Global modeling shows sepsis cases and deaths surged in 2020–2021, reversing prior gains and highlighting rising burden among older adults and as a complication of non-infectious diseases. Integrative neonatal microbiome-metabolome data link probiotic-driven ecosystem shifts and bacterial fermentation products to late-onset sepsis risk. Preclinical work identifies dihydroartemisinin as a candidate therapy for sepsis-associated encephalopathy via microglial ferroptosis modulation.
Summary
Global modeling shows sepsis cases and deaths surged in 2020–2021, reversing prior gains and highlighting rising burden among older adults and as a complication of non-infectious diseases. Integrative neonatal microbiome-metabolome data link probiotic-driven ecosystem shifts and bacterial fermentation products to late-onset sepsis risk. Preclinical work identifies dihydroartemisinin as a candidate therapy for sepsis-associated encephalopathy via microglial ferroptosis modulation.
Research Themes
- Global sepsis epidemiology and policy prioritization
- Microbiome-metabolite signatures predicting neonatal late-onset sepsis
- Neuroinflammation and ferroptosis as targets in sepsis-associated encephalopathy
Selected Articles
1. Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis.
Using GBD 2021 data across 149 million deaths and 250 million hospital admissions, the authors estimate 166 million sepsis cases and 21.4 million sepsis-related deaths (31.5% of all deaths) in 2021. Progress from 1990 to 2019 reversed in 2020–2021, with rising incidence and mortality among adults—especially those aged ≥70 years—and increasing sepsis as a complication of non-infectious underlying causes (e.g., stroke, COPD, cirrhosis).
Impact: Provides the most comprehensive, post-pandemic global update on sepsis burden, quantifying shifts by age, syndrome, and underlying causes. It reframes sepsis as a common terminal pathway of non-infectious diseases, informing policy and prevention priorities.
Clinical Implications: Guides resource allocation toward older adults and chronic disease populations, emphasizes prevention of bloodstream and lower respiratory infections (including COVID-19) in non-infectious disease care pathways, and underscores the need for surveillance systems that capture implicit sepsis.
Key Findings
- In 2021, an estimated 166 million sepsis cases and 21.4 million sepsis-related deaths occurred, accounting for 31.5% of all global deaths.
- Progress from 1990 to 2019 reversed, with a surge in sepsis burden in 2020–2021.
- Adults ≥15 years experienced increased incidence (230% since 1990) and mortality (26.3%), with 9.28 million deaths among those ≥70 years.
- Sepsis increasingly complicates non-infectious underlying causes (notably stroke, COPD, and cirrhosis).
- Bloodstream infections and lower respiratory infections (including COVID-19) are predominant infectious syndromes in sepsis-related deaths.
Methodological Strengths
- Integration of multiple data sources (cause-of-death, hospital, tissue sampling, linked records) across 4290 location-years.
- Explicit and implicit sepsis capture with age–sex–location modeling over 1990–2021.
Limitations
- Model-based estimates depend on data quality and assumptions; under-ascertainment likely in low-resource settings.
- Potential misclassification when identifying implicit sepsis from coding patterns.
Future Directions: Enhance sepsis surveillance linking hospital EHRs with vital statistics; target prevention for older adults and those with chronic non-infectious diseases; evaluate the impact of vaccination and infection control on sepsis endpoints.
BACKGROUND: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. METHODS: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths.
2. Bacterial metabolite patterns of infants receiving multi-strain probiotics and risk of late-onset sepsis.
Leveraging a policy-driven natural experiment in VLBW infants, probiotic supplementation (B. longum subsp. infantis plus L. acidophilus) shifted gut communities toward beneficial taxa and away from nosocomial pathobionts. Notably, prior to LOS diagnosis, probiotic-exposed infants showed significantly lower concentrations of B. longum fermentation products (e.g., acetate) than matched non-LOS cases, linking metabolite signatures to imminent sepsis risk.
Impact: Integrates metagenomics and metabolomics to reveal pre-sepsis metabolic signatures and ecosystem shifts in a high-risk neonatal population, informing both mechanistic understanding and potential early-warning biomarkers.
Clinical Implications: Supports targeted microbiome monitoring and metabolite-based risk stratification for LOS in VLBW infants and suggests that probiotic strategies should consider functional metabolite outputs, not just taxonomic shifts.
Key Findings
- Unit policy to administer B. longum subsp. infantis plus L. acidophilus enabled a natural experiment (97 infants post-change, 78 pre-change; LOS cases 38 vs 32).
- Probiotic supplementation increased beneficial taxa and reduced nosocomial pathobionts such as Klebsiella spp.
- Before LOS diagnosis, probiotic-exposed infants exhibited significantly lower concentrations of B. longum fermentation products (e.g., acetate) than matched non-LOS cases.
Methodological Strengths
- Natural experiment leveraging a unit-level policy change.
- Integrated metagenomic and metabolomic profiling with matched comparisons.
Limitations
- Single-center design limits generalizability; observational nature precludes causal inference.
- Incomplete reporting of effect sizes and p-values in abstract; potential residual confounding.
Future Directions: Prospective multicenter validation of metabolite-based early warning models, mechanistic studies linking specific fermentation pathways to host immunity, and RCTs testing timing/formulation of probiotics in VLBW infants.
The effect of multi-strain probiotics containing Bifidobacterium longum (B. longum) on late-onset sepsis (LOS) risk in very-low-birth-weight infants (VLBWIs; birth weight < 1,500 g) remains uncertain. In a single-center study, we analyzed intestinal metagenome and metabolome data in VLBWIs during the period of highest vulnerability of LOS. Using a unit's policy change to routinely administer B. longum subspecies infantis plus Lactobacillus acidophilus as natural experiment, we compared 97 infants (including 38 LOS cases) after change with 78 infants (including 32 LOS cases) before. Probiotic supplementation was associated with more beneficial bacteria and reduced abundance of nosocomial pathobionts, such as Klebsiella spp. Infants in the probiotic group had significantly lower concentrations of B. longum fermentation products prior to sepsis diagnosis than matched non-LOS cases (acetate: p
3. Dihydroartemisinin alleviates sepsis-associated encephalopathy by reducing microglial iron accumulation and mitochondrial dysfunction via HIF1A/HMOX1 pathway.
Dihydroartemisinin bound HIF1A, crossed the blood–brain barrier, and improved survival, sepsis scores, neuroinflammation, and cognition in CLP-induced SAE. It reduced microglial ferroptosis (lipid peroxidation, Fe2+, ROS) and mitochondrial dysfunction (TMRE, mtDNA) while downregulating HIF1A/HMOX1 and modulating SLC7A11/GPX4 in hippocampal microglia.
Impact: Identifies a mechanistic, druggable pathway—microglial ferroptosis via HIF1A/HMOX1—linking sepsis to brain dysfunction and demonstrates a repurposable compound with blood–brain barrier penetration and multi-system validation.
Clinical Implications: Positions dihydroartemisinin as a potential candidate for SAE, motivating dose-finding and safety trials, and supports ferroptosis-targeted strategies as adjuncts to sepsis care.
Key Findings
- Network pharmacology and transcriptomics identified HIF1A/HMOX1 as core DHA-related pathways; docking, MDS, and SPR confirmed strong DHA–HIF1A binding.
- LC/MS demonstrated DHA penetration into the hippocampus across the blood–brain barrier.
- In CLP-induced SAE, DHA improved survival, sepsis scores, cognitive function, and reduced neuroinflammation.
- DHA inhibited microglial ferroptosis (reduced lipid peroxidation, Fe2+, ROS) and mitochondrial dysfunction (improved TMRE, mtDNA content), with downregulation of HIF1A/HMOX1 and modulation of SLC7A11/GPX4.
Methodological Strengths
- Convergent validation across in silico (docking/MDS), biophysical (SPR), in vitro (BV2), and in vivo (CLP) systems.
- Behavioral, survival, histologic, and molecular endpoints enhance mechanistic rigor.
Limitations
- Preclinical study; human dosing, safety, and efficacy are unknown.
- Sample sizes and randomization/blinding details are not specified in the abstract.
Future Directions: Define pharmacokinetics/pharmacodynamics and optimal dosing in larger animal models, assess safety, and conduct early-phase clinical trials for SAE with ferroptosis-related biomarkers as endpoints.
BACKGROUND: Sepsis-associated encephalopathy (SAE) refers to acute brain dysfunction caused by sepsis without direct central nervous system infection, in which microglia plays a pivotal role. Microglial ferroptosis is one of the key drivers of SAE. Dihydroartemisinin (DHA) is a natural product with anti-inflammatory effects and associated with ferroptosis. However, no current studies indicating that DHA plays a role in SAE or microglial ferroptosis, and further exploration is needed. OBJECTIVE: To investigate therapeutic effects of DHA on SAE induced by caecal ligation and puncture (CLP), and its regulation of microglial ferroptosis. METHODS: Network pharmacology, transcriptome sequencing, and bioinformatics were used to identify potential pathways and core DHA targets for SAE treatment. Molecular docking, molecular dynamics simulations (MDS) and Surface plasmon resonance (SPR) were performed to validate these targets. Models were created in vitro and in vivo utilizing lipopolysaccharide (LPS)-stimulated BV2 cells and CLP, respectively, to assess the therapeutic benefits of DHA. The in vivo therapeutic effectiveness of DHA was assessed using behavioral tests, survival analysis, and hematoxylin and eosin and Nissl staining. To validate important pathways and targets, RT-qPCR, immunofluorescence, Western blotting, ELISA, and flow cytometry were used.