Revolution in sepsis: a symptoms-based to a systems-based approach? DOI Creative Commons
Geoffrey P. Dobson, Hayley L. Letson, Jodie L. Morris

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: May 30, 2024

Abstract Severe infection and sepsis are medical emergencies. High morbidity mortality linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy multiple organ dysfunction. Males appear have a higher risk of than females. Currently, there few or no effective drug therapies protect the brain, maintain blood brain barrier, resolve inflammation reduce secondary injury in other vital organs. We propose major reason for lack progress is consequence treat-as-you-go, single-nodal target approach, rather more integrated, systems-based approach. A new revolution required better understand how body responds an infection, identify markers detect its progression discover system-acting drugs treat it. In this review, we present brief history followed by pathophysiology from systems’ perspective future opportunities. argue that targeting body’s early immune-driven CNS-response may improve patient outcomes. If barrage PAMPs DAMPs can be reduced early, CNS-organ circuits (or axes) will preserved reduced. been developing systems-based, small-volume, fluid therapy comprising adenosine, lidocaine magnesium (ALM) endotoxemia. Our studies indicate ALM shifts sympathetic parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces corrects coagulopathy, tissue O 2 supply. Future research investigate potential translation humans.

Language: Английский

Synbiotic combination of 2’-Fucosyllactose and Bifidobacterium mitigates neurodevelopmental disorders and ASD-like behaviors induced by Valproic Acid DOI
Ying He, Bo Zhang, Xin Yu

et al.

Food & Function, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders characterized by social deficits and repetitive behaviors. Increasing evidence suggests that the gut microbiota influences neurodevelopment behavior. In this study, we established an ASD model administering valproic acid (VPA) to pregnant females, with male offspring receiving daily synbiotic intervention for four weeks post-weaning. The results indicate combination 2'-Fucosyllactose (2'-FL) Bifidobacterium animalis subsp. lactis BB-12 (BB-12) outperformed 2'-FL Lactobacillus paracasei L9300BH (L9300BH) in alleviating deficits, behaviors, neuronal damage, dysregulated expression social-related genes neuroinflammatory markers mice. Additionally, improved morphology barrier integrity, reduced inflammation, optimized structure increasing abundance Bifidobacteria Akkermansia, known producers short-chain fatty acids (SCFAs). Notably, levels acetate, propionate, butyrate were significantly elevated fecal samples. summary, supports homeostasis, enhances SCFA levels, mitigates abnormalities

Language: Английский

Citations

1

The Core‐Shell Microneedle with Probiotic Extracellular Vesicles for Infected Wound Healing and Microbial Homeostasis Restoration DOI Open Access
Fangfang Qi, Yujie Xu, Bowen Zheng

et al.

Small, Journal Year: 2024, Volume and Issue: 20(46)

Published: Aug. 7, 2024

Abstract Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing viable treatment needs across different stages critical challenge in wound management. Herein, novel core‐shell microneedle (CSMN) patch designed for sequential delivery tannic acid‐magnesium (TA‐Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application sites, CSMN@TA‐Mg/LDEV releases TA‐Mg first counteract pathogenic overload reduce reactive oxygen species (ROS), aiding proliferative phase. Subsequently, sustained release LDEVs enhances activities keratinocytes fibroblasts, promotes vascularization, modulates collagen deposition. Notably, track composition demonstrates that can both inhibit aggressive pathogen increase diversity at sites. Functional analysis further highlights potential facilitating skin barrier restoration. Moreover, it confirmed accelerate closure improve post‐recovery quality murine wound. Conclusively, this innovative CSMN offers rapid high‐quality alternative emphasizes significance homeostasis.

Language: Английский

Citations

8

Integrating research on bacterial pathogens and commensals to fight infections—an ecological perspective DOI Creative Commons
Lisa Maier, Christoph K. Stein‐Thoeringer, Ruth E. Ley

et al.

The Lancet Microbe, Journal Year: 2024, Volume and Issue: 5(8), P. 100843 - 100843

Published: April 9, 2024

The incidence of antibiotic-resistant bacterial infections is increasing, and development new antibiotics has been deprioritised by the pharmaceutical industry. Interdisciplinary research approaches, based on ecological principles fitness, competition, transmission, could open avenues to combat infections. Many facultative pathogens use human mucosal surfaces as their major reservoirs induce infectious diseases aid lateral transmission host organisms under some pathological states microbiome host. Beneficial commensals can outcompete specific pathogens, thereby lowering capacity spread cause serious Despite clinical relevance, however, understanding commensal–pathogen interactions in natural habitats remains poor. In this Personal View, we highlight directions intensify between context microbiomes biology that lead innovative sustainable ways preventing treating diseases.

Language: Английский

Citations

7

Assessing phage-host population dynamics by reintroducing virulent viruses to synthetic microbiomes DOI Creative Commons
Jacob Wilde,

Randy Boyes,

Avery Robinson

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(5), P. 768 - 778.e9

Published: April 22, 2024

Microbiomes feature complex interactions between diverse bacteria and bacteriophages. Synthetic microbiomes offer a powerful way to study these interactions; however, major challenge is obtaining representative bacteriophage population during the bacterial isolation process. We demonstrate that colony reliably excludes virulent viruses from sample sources with low virion-to-bacteria ratios such as feces, creating "virulent virus-free" controls. When dsDNA virome reintroduced 73-strain synthetic gut microbiome in bioreactor model of human colon, target susceptible strains without significantly altering community structure or metabolism. In addition, we detected signals prophage induction associate predation. Overall, our findings indicate dilution-based methods generate are heavily depleted, if not devoid, viruses, reintroduced, have targeted effect on assembly, metabolism, replication.

Language: Английский

Citations

7

Revolution in sepsis: a symptoms-based to a systems-based approach? DOI Creative Commons
Geoffrey P. Dobson, Hayley L. Letson, Jodie L. Morris

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: May 30, 2024

Abstract Severe infection and sepsis are medical emergencies. High morbidity mortality linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy multiple organ dysfunction. Males appear have a higher risk of than females. Currently, there few or no effective drug therapies protect the brain, maintain blood brain barrier, resolve inflammation reduce secondary injury in other vital organs. We propose major reason for lack progress is consequence treat-as-you-go, single-nodal target approach, rather more integrated, systems-based approach. A new revolution required better understand how body responds an infection, identify markers detect its progression discover system-acting drugs treat it. In this review, we present brief history followed by pathophysiology from systems’ perspective future opportunities. argue that targeting body’s early immune-driven CNS-response may improve patient outcomes. If barrage PAMPs DAMPs can be reduced early, CNS-organ circuits (or axes) will preserved reduced. been developing systems-based, small-volume, fluid therapy comprising adenosine, lidocaine magnesium (ALM) endotoxemia. Our studies indicate ALM shifts sympathetic parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces corrects coagulopathy, tissue O 2 supply. Future research investigate potential translation humans.

Language: Английский

Citations

7