Related Experiment Video
Updated: Jun 26, 2026
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis
Lei Peng1, Honghao Song1, Huijing Shi1
1Department of Anesthesiology, Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai 200003, People's Republic of China.
Abstract:
Sepsis-induced pulmonary injury represents a life-threatening global health challenge due to poorly defined pathological mechanisms. The gut-lung axis has been proven to be widely involved in sepsis-induced lung injury, yet effective interventions targeting gut microbiota homeostasis remain unknown. Single-cell sequencing revealed increased alveolar apoptosis and impaired macrophage efferocytosis during sepsis pathogenesis. Thus, we designed oral manganese-doped carbon dots (Mn-CDs) to alleviate septic lung injury by remodeling gut microbiota homeostasis and targeting the gut-lung axis. Biochemical characterization demonstrated Mn-CDs possess multienzyme mimetic activities (SOD-, CAT-, POD-, GPx-like) and potent ROS scavenging capacity. In murine sepsis models, Mn-CDs significantly improved systemic indices and were associated with macrophage anti-inflammatory states with enhanced efferocytosis, as evidenced by transcriptomic profiling. Integrated metagenomic/metabolomic analyses identified Mn-CDs-mediated enrichment of g_Clostridium and g_Bacteroides, concomitant with elevated indole-3-propionic acid (IPA) production. Subsequent in vitro studies demonstrate that IPA likely binds primarily to the aryl hydrocarbon receptor (AHR), promoting both efferocytosis and anti-inflammatory polarization in macrophages, thereby mitigating septic lung injury. Notably, the fecal microbiota transplantation (FMT) from Mn-CDs-treated mice not only alleviated systemic symptoms but also effectively promoted efferocytic polarization of pulmonary macrophages in septic mice. Depletion of the gut microbiota resulted in a significant loss of the protective efficacy of Mn-CDs in a murine model of septic lung injury. Collectively, the gut-lung axis mediated by microbiota-derived IPA and macrophage efferocytosis contributes to the remediation of septic lung injury, highlighting the potential of Mn-CDs in microbiome-directed critical care.
Insights
Manganese-doped carbon dots (Mn-CDs) treat sepsis-induced lung injury by restoring gut bacteria and enhancing macrophage efferocytosis via indole-3-propionic acid (IPA). This highlights the gut-lung axis for critical care interventions.
Area of Science:
- Biomedical Engineering
- Microbiology
- Immunology
Background:
- Sepsis-induced pulmonary injury is a critical condition with unclear pathology.
- The gut-lung axis plays a role in sepsis-induced lung injury, but effective interventions are lacking.
- Single-cell sequencing shows increased alveolar apoptosis and reduced macrophage efferocytosis in sepsis.
Purpose of the Study:
- To design oral manganese-doped carbon dots (Mn-CDs) for treating septic lung injury.
- To investigate Mn-CDs' effects on gut microbiota homeostasis and the gut-lung axis.
- To elucidate the mechanisms underlying Mn-CDs' therapeutic potential in sepsis.
Main Methods:
- Biochemical characterization of Mn-CDs for enzyme mimetic activities and ROS scavenging.
- Establishment of murine sepsis models to evaluate Mn-CDs' efficacy.
- Transcriptomic, metagenomic, and metabolomic analyses to identify molecular mechanisms.
- In vitro studies using macrophages and fecal microbiota transplantation (FMT).
Main Results:
- Mn-CDs exhibited SOD-, CAT-, POD-, and GPx-like activities and potent ROS scavenging.
- Mn-CDs improved systemic indices in sepsis models, promoting anti-inflammatory macrophages with enhanced efferocytosis.
- Mn-CDs enriched gut bacteria like Clostridium and Bacteroides, increasing indole-3-propionic acid (IPA) production.
- IPA promoted macrophage efferocytosis and anti-inflammatory polarization via the aryl hydrocarbon receptor (AHR).
- FMT from Mn-CDs-treated mice alleviated sepsis symptoms and enhanced pulmonary macrophage efferocytosis.
- Gut microbiota depletion abrogated Mn-CDs' protective effects.
Conclusions:
- The gut-lung axis, mediated by microbiota-derived IPA and macrophage efferocytosis, is crucial for mitigating septic lung injury.
- Mn-CDs represent a promising microbiome-directed therapeutic strategy for critical care, targeting the gut-lung axis.
- This study highlights the potential of Mn-CDs in managing sepsis-induced pulmonary injury through gut microbiota modulation.
Related Concept Videos
01:24Microbes and Other Elemental Cycles
01:24Microbial Corrosion