Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation

Chen, Xia; Wu, Rong; Li, Lei; Zeng, Yunong; Chen, Jingrui; Wei, Mingyuan; Feng, Ying; Chen, Guiming; Wang, Yuhang; Lin, Lizhen; Luo, Haihua; Chen, A‐Li; Zeng, Zhenhua; He, Fangjie; Bai, Yang; Zhang, Siyou; Han, Yubing; Wang, Zhang; Zhao, Xiaoshan; Xiao, Wei; Jiang, Yong; Gong, Shenhai

doi:10.1016/j.immuni.2023.01.015

Cited by 47 publications

(17 citation statements)

References 51 publications

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“…Animal studies have shown that increased serum Mg 2+ levels occur after acute stress stimulus exposure (20,30). We observed a positive correlation between circulating histones and Mg 2+ levels in septic patients and mice, and a significant increase in serum Mg 2+ levels in mice injected intravenously with histones, which might be related to histone-mediated stress damage.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Sulfate Ameliorates Histone-Induced Coagulation Dysfunction and Lung Damage in Mice

Zhong,

Zhang,

Chen

et al. 2023

Shock

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Introduction Extracellular histones have been determined as significant mediators of sepsis, which can induce endothelial cell injury and promote coagulation activation, and ultimately contribute to multiorgan failure (MOF). Evidence suggests that magnesium sulfate (MgSO4) exerts a potential coagulation-modulating activity; however, whether MgSO4 ameliorates histone-induced coagulation dysfunction and organ damage remains unclear. Methods To measure circulating histone levels, blood specimens were collected from septic patients and mice, and the relationship between circulating histone levels, coagulation parameters, and Mg2+ levels in sepsis was investigated. Furthermore, to explore the possible protective effects of MgSO4, we established a histone-induced coagulation model in mice by intravenous histone injection. The survival rate of mice was assessed, and the histopathological damage of the lungs (including endothelial cell injury and coagulation status) was evaluated using various methods, including HE staining, immunohistochemistry, immunofluorescence, electron microscopy, and Q-PCR. Results The circulating histone levels in septic patients and mice were significantly associated with several coagulation parameters. In septic patients, histone levels correlated negatively with platelet counts and positively with prothrombin time and D-dimer levels. Similarly, in cecal ligation and puncture (CLP) mice, histones correlated negatively with platelet counts and positively with D-dimer levels. Interestingly, we also observed a positive link between histones and Mg2+ levels, suggesting that Mg2+ with anticoagulant activity is involved in histone-mediated coagulation alterations in sepsis. Further animal experiments confirmed that MgSO4 administration significantly improved survival and attenuated histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage in mice. Conclusion These results suggest that therapeutic targeting of histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage, for example with MgSO4, may be protective in septic individuals with elevated circulating histone levels.

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Section: Discussionmentioning

confidence: 99%

Magnesium Sulfate Ameliorates Histone-Induced Coagulation Dysfunction and Lung Damage in Mice

Zhong,

Zhang,

Chen

et al. 2023

Shock

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“…162,163 Innate immune system and T-cell development during early life may have particular importance in establishing antigen tolerance, [164][165][166] further highlighting the importance of early microbial colonization in infancy and childhood on lifelong health. 167 Changes in immune function occurring at subsequent life stages including pregnancy 168 may also disrupt the balance between microbes and the innate immune system. In addition, dietary factors, including the intake of sodium, can affect host:microbe homeostasis, leading to the activation of T H 17 cells, promoting the formation of proinflammatory isolevuglandins and increased risk of hypertension.…”

Section: Commensal Microbiota and Innate Immune Functionmentioning

confidence: 99%

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Gabriel

Ferguson

2023

Circulation Research

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Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and adulthood. Effects of microbiota, both during early development, and in later life, may induce changes in host metabolism that modulate risk mechanisms and predispose toward the development of cardiometabolic disease. In this review, we summarize the factors that influence gut microbiome composition and function during early life and explore how changes in microbiota and microbial metabolism influence host metabolism and cardiometabolic risk throughout life. We highlight limitations in current methodology and approaches and outline state-of-the-art advances, which are improving research and building toward refined diagnosis and treatment options in microbiome-targeted therapies.

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“…Pyroptosis activation can effectively inhibit tumor growth, while its inhibition can alleviate certain non-neoplastic diseases. [85,165,166] Recent studies have shown that excessive pyroptosis plays a role in the occurrence and progression of various diseases. [167] Hence, nanomaterials provide a promising therapeutic strategy to control pyroptosis by modulating its triggering conditions or inhibiting key factors in the pathway.…”

Section: Pyroptosis Inhibitors For Non-neoplastic Disease Therapymentioning

confidence: 99%

Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway

Wang

2023

Adv Healthcare Materials

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Pyroptosis differs significantly from apoptosis and cell necrosis as an alternative mode of programmed cell death. Its occurrence is mediated by the gasdermin protein, leading to characteristic outcomes including cell swelling, membrane perforation, and release of cell contents. Research underscores the role of pyroptosis in the etiology and progression of many diseases, making it a focus of research intervention as scientists explore ways to regulate pyroptosis pathways in disease management. Despite numerous reviews detailing the relationship between pyroptosis and disease mechanisms, few delve into recent advancements in nanomaterials as a mechanism for modulating the pyroptosis pathway to mitigate disease effects. Therefore, there is an urgent need to fill this gap and elucidate the path for the use of this promising technology in the field of disease treatment. This review article delves into recent developments in nanomaterials for disease management through pyroptosis modulation, details the mechanisms by which drugs interact with pyroptosis pathways, and highlights the promise that nanomaterial research holds in driving forward disease treatment.

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Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation

Cited by 47 publications

References 51 publications

Magnesium Sulfate Ameliorates Histone-Induced Coagulation Dysfunction and Lung Damage in Mice

Magnesium Sulfate Ameliorates Histone-Induced Coagulation Dysfunction and Lung Damage in Mice

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway

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