In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation

Li, Xiaoyü; Qu, Shaoqi; Song, Xiangbin; Wu, Congming; Shen, Jianzhong; Zhu, Kui

doi:10.1002/advs.202302950

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…Recently, Li et al . proposed an all-in-one drug delivery strategy equipped with bactericidal, LPS neutralization, and detoxification activities to treat sepsis-associated infections and hyperinflammation [59]. Our study also highlighted the important role of endogenous gut-derived LPS induced by Leptospira infection.…”

Section: Discussionmentioning

confidence: 79%

“…Our results showed that doxycycline treatment significantly reduced the leptospiral load in the blood in severe leptospirosis; however, the gene expression of proinflammatory cytokines was upregulated, which was consistent with the Jarisch-Herxheimer Reaction [5] . Recently, Li et al proposed an all-in-one drug delivery strategy equipped with bactericidal, LPS neutralization, and detoxification activities to treat sepsis-associated infections and hyperinflammation [59] . Our study also highlighted the important role of endogenous gut-derived LPS induced by Leptospira infection.…”

Section: Discussionmentioning

confidence: 99%

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Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Xie,

Chen,

Zhang

et al. 2024

Preprint

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Leptospirosis is an emerging infectious disease caused by pathogenicLeptospiraspp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed thatLeptospirainfection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated LPS levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines afterLeptospirainfection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription ofTNF-α,IL-1β,IL-10, andTLR4in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Xie,

Chen,

Zhang

et al. 2024

Preprint

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“…The use of endotoxins and their purified derivative LPS as immunomodulating agents is severely limited by their ability to induce clinical symptoms, including shock, fever, shaking chills, bronchoconstriction and changes in the level of nonspecific bronchial hyperresponsiveness [36]. Therefore, numerous attempts using physical, chemical or biosynthetic engineering approaches have been made to attenuate LPS and to separate endotoxic and immunostimulatory activities [37][38][39][40][41]. Moreover, ionizing radiation ( 60 Co-gamma) has also been used for the detoxification of LPS [42].…”

Section: Introductionmentioning

confidence: 99%

Radiation-Detoxified Form of Endotoxin Effectively Activates Th1 Responses and Attenuates Ragweed-Induced Th2-Type Airway Inflammation in Mice

Bácsi,

Ágics,

Pázmándi

et al. 2024

IJMS

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Urbanization with reduced microbial exposure is associated with an increased burden of asthma and atopic symptoms. Conversely, environmental exposure to endotoxins in childhood can protect against the development of allergies. Our study aimed to investigate whether the renaturation of the indoor environment with aerosolized radiation-detoxified lipopolysaccharide (RD-LPS) has a preventative effect against the development of ragweed-induced Th2-type airway inflammation. To explore this, cages of six-week-old BALB/c mice were treated daily with aerosolized native LPS (N-LPS) or RD-LPS. After a 10-week treatment period, mice were sensitized and challenged with ragweed pollen extract, and inflammatory cell infiltration into the airways was observed. As dendritic cells (DCs) play a crucial role in the polarization of T-cell responses, in our in vitro experiments, the effects of N-LPS and RD-LPS were compared on human monocyte-derived DCs (moDCs). Mice in RD-LPS-rich milieu developed significantly less allergic airway inflammation than mice in N-LPS-rich or common environments. The results of our in vitro experiments demonstrate that RD-LPS-exposed moDCs have a higher Th1-polarizing capacity than moDCs exposed to N-LPS. Consequently, we suppose that the aerosolized, non-toxic RD-LPS applied in early life for the renaturation of urban indoors may be suitable for the prevention of Th2-mediated allergies in childhood.

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Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis

Zhang,

Yang,

Zhou

et al. 2024

Front. Med.

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BackgroundThe association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.MethodsOriginal articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.ResultsA total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. “Nutrients” had the highest number of publications, while “Frontiers in Cellular and Infection Microbiology,” “Frontiers in Immunology” and “the International Journal of Molecular Sciences” have shown increasing attention to this field in the past 2 years. Author keywords appearing more than 100 times included “gut microbiota (GM),” “sepsis” and “microbiota.” Finally, this study identified “lipopolysaccharides (LPS),” “short-chain fatty acids (SCFAs),” “probiotics,” “fecal microbiota transplantation (FMT)” and “gut-liver axis” as the research hotspots and potential frontier directions in this field.ConclusionThis bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.

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In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation

Cited by 6 publications

References 56 publications

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe leptospirosis

Radiation-Detoxified Form of Endotoxin Effectively Activates Th1 Responses and Attenuates Ragweed-Induced Th2-Type Airway Inflammation in Mice

Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis

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