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

Microbiome diversity protects against pathogens by nutrient blocking DOI
Frances Spragge, Erik Bakkeren, Martin T. Jahn

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6676)

Published: Dec. 14, 2023

The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack ability to predict which communities will be protective. We studied how bacteria influence two major bacterial both vitro and gnotobiotic mice. Whereas single species alone had negligible effects, resistance greatly increased with community diversity. Moreover, this community-level rested critically upon certain being present. explained these ecological patterns through collective resistant consume nutrients that overlap those used pathogen. Furthermore, applied our findings successfully resist a novel target strain. Our work provides reason why diversity is beneficial suggests route for rational design pathogen-resistant communities.

Language: Английский

Citations

166
Microbial transmission in the social microbiome and host health and disease DOI Creative Commons
Amar Sarkar,

Cameron J.A. McInroy,

Siobhán Harty

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(1), P. 17 - 43

Published: Jan. 1, 2024

Language: Английский

Citations

38
The conceptual foundations of innate immunity: Taking stock 30 years later DOI Creative Commons
Thomas Pradeu, Bart P. H. J. Thomma, Stephen E. Girardin

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 613 - 631

Published: April 1, 2024

SummaryWhile largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding immunology. Innate provides first barrier infection in vertebrates, and it is sole mechanism host defense invertebrates plants. also plays a critical role maintaining homeostasis, shaping microbiota, disease contexts such as cancer, neurodegeneration, metabolic syndromes, aging. The emergence field has led an expanded view system, no longer restricted vertebrates instead concerns all metazoans, plants, even prokaryotes. study given rise new concepts language. Here, we review history definition core immunity, discussing their value fruitfulness long run.

Language: Английский

Citations

36
Commensal consortia decolonize Enterobacteriaceae via ecological control DOI Creative Commons
Munehiro Furuichi, Takaaki Kawaguchi, Marie‐Madlen Pust

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, may perpetuate dysregulated immunity tissue damage

Language: Английский

Citations

27
Host control of the microbiome: Mechanisms, evolution, and disease DOI Creative Commons
Jacob Wilde, Emma Slack, Kevin R. Foster

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6706)

Published: July 18, 2024

Many species, including humans, host communities of symbiotic microbes. There is a vast literature on the ways these microbiomes affect hosts, but here we argue for an increased focus how hosts their microbiomes. Hosts exert control over symbionts through diverse mechanisms, immunity, barrier function, physiological homeostasis, and transit. These mechanisms enable to shape ecology evolution generate natural selection microbial traits that benefit host. Our result from perpetual tension between symbiont evolution, can leverage host's evolved abilities regulate microbiota prevent treat disease. The study will be central our ability both understand manipulate microbiotas better health.

Language: Английский

Citations

26
Bacillus siamensis Targeted Screening from Highly Colitis-Resistant Pigs Can Alleviate Ulcerative Colitis in Mice DOI Creative Commons

Xiuyu Fang,

Haiyang Liu,

Yongqing Du

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of epithelial structures, which are closely associated with changes in the microbiota. We previously revealed that Min pigs, a native Chinese breed, more resistant to dextran sulfate sodium (DSS)-induced than commercial Yorkshire pigs. Characterizing microbiota pigs would allow identification core microbes confer resistance. By analyzing linked disease course we observed

Language: Английский

Citations

22
Growth of microbes in competitive lifestyles promotes increased ARGs in soil microbiota: insights based on genetic traits DOI Creative Commons
Zishu Liu,

Xiangwu Yao,

Cheng‐Yi Chen

et al.

Microbiome, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 13, 2025

The widespread selective pressure of antibiotics in the environment has led to propagation antibiotic resistance genes (ARGs). However, mechanisms by which microbes balance population growth with enrichment ARGs remain poorly understood. To address this, we employed microcosm cultivation at different (i.e., Oxytetracycline, OTC) stresses across concentrations from environmental clinical. Paired shot-gun metagenomics analysis and quantification bacterial growth, trait-based assessment soil microbiota was applied reveal association between key ARG subtypes, representative taxa, functional-gene features that drive ARGs. Our results illuminate resistome variation is closely associated growth. A non-monotonic change abundance richness observed over a concentration gradient none 10 mg/l. Soil exposed intermediate OTC 0.1 0.5 mg/l) showed greater increases total Community compositionally, i.e., Pseudomonadaceae considered boost increase It chromosomally carried kinds multidrug such as mexAB-oprM mexCD-oprJ could mediate intrinsic OTC. Streptomycetaceae shown better adaptive ability than other clinical concentrations. it contributed less represents stress-tolerant lifestyle grows slowly carries fewer In terms community genetic features, aggregated traits further indicates enhancement resource acquisition yield driving abundance. Moreover, optimizations energy production conversion, alongside streamlining bypass metabolic pathways, sub-inhibitory conditions. this study suggest competitive lifestyles are selected under stress nutrient scarcity. They possess substrate utilization capacity carry more ARGs, due they were faster growing leading This expanded application assessments understanding ecology propagation. And finding illustrated changes accompanied switching microbiome, theoretically supports control approach based on principle species exclusion.

Language: Английский

Citations

4
Monosaccharides drive Salmonella gut colonization in a context-dependent or -independent manner DOI Creative Commons
Christopher Schubert, Bidong D. Nguyen, Andreas Sichert

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 18, 2025

Language: Английский

Citations

4
Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era DOI Creative Commons
Xinjun Wang, Di Zhao, Dexi Bi

et al.

Science Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms DOI Creative Commons
Lisa Osbelt, Éva Almási,

Marie Wende

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(7), P. 1792 - 1811

Published: June 11, 2024

The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. strains can produce enterotoxins, namely, tilimycin tilivalline, while also contributing to colonization resistance (CR). relationship between these seemingly contradictory roles not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis various mouse models, we show that provides CR against Salmonella Typhimurium. In vitro, antimicrobial activity depended on production was induced simple carbohydrates. vivo, toxin in germ-free mice, it largely toxin-independent mice residual microbiota. This linked relative levels toxin-inducing carbohydrates vivo. Finally, dulcitol utilization essential for gnotobiotic mice. Together, this demonstrates nutrient availability key both toxin-dependent substrate-driven competition Salmonella.

Language: Английский

Citations

16