Contribution of gut microbiota toward renal function in sepsis

Xu, Yaya; Kong, Xiangmei; Zhu, Yue; Xu, Jiayue; Mao, Haoyun; Li, Jiru; Zhang, Jianhua; Zhu, Xiaoyan

doi:10.3389/fmicb.2022.985283

Cited by 9 publications

(8 citation statements)

References 117 publications

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“…Studies have shown that dysbiosis of the gut microbiota could exacerbate AKI [22,23]. Therefore, we utilized the 16S rRNA technique to examine the gut flora of each group of mice.…”

Section: Discussionmentioning

confidence: 99%

Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism

Xiang,

Wang,

Yang

et al. 2023

Molecules

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Acute kidney injury (AKI) is a complication of a wide range of serious illnesses for which there is still no better therapeutic agent. We demonstrated that M-18C has a favorable inhibitory effect on monoacylglycerol lipase (MAGL), and several studies have demonstrated that nerve inflammation could be effectively alleviated by inhibiting MAGL, suggesting that M-18C has good anti-inflammatory activity. In this study, we investigated the effect of M-18C on LPS-induced acute kidney injury (AKI), both in vivo and in vitro, by using liquid chromatography-mass spectrometry (LC-MS), 16S rRNA gene sequencing, Western blot, and immunohistochemistry. The results showed that both in vivo and in vitro M-18C reduced the release of TNF-α and IL-1β by inhibiting the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) protein; in addition, M-18C was able to intervene in LPS-induced AKI by ameliorating renal pathological injury, repairing the intestinal barrier, and regulating gut bacterial flora and serum metabolism. In conclusion, this study suggests that M-18C has the potential to be a new drug for the treatment of AKI.

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“…Studies have shown that dysbiosis of the gut microbiota could exacerbate AKI [22,23]. Therefore, we utilized the 16S rRNA technique to examine the gut flora of each group of mice.…”

Section: Discussionmentioning

confidence: 99%

Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism

Xiang,

Wang,

Yang

et al. 2023

Molecules

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“…and Candida albicans [26,27]. This combination of increased permeability and overgrowth of potentially harmful pathogens at the mucosal surface results in a ‘leaky gut’, in which toxins and bacteria penetrate the systemic circulation, promote pathological systemic inflammation, and drives multiorgan dysfunction as seen in the lungs [28], kidney [29] and the brain [30 ▪ ]. Prevention or restoration of the intestinal microbial ecosystems might, therefore, be key in breaking the vicious circle that leads to the immune dysregulation and organ dysfunction that is the hallmark of sepsis.…”

Section: Microbiota-mediated Immunomodulation and Sepsis Pathophysiologymentioning

confidence: 99%

Leveraging the microbiome in the treatment of sepsis: potential pitfalls and new perspectives

Biemond

McDonald

Haak

2023

Current Opinion in Critical Care

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Purpose of reviewThis review aims to provide an overview of the current knowledge about microbiota-targeted therapies in sepsis, and calls out – despite recent negative studies – not to halt our efforts of translating these tools into regular medical practice.Recent findingsThe intestinal microbiome has an important role in shaping our immune system, and microbiota-derived metabolites prime innate and adaptive inflammatory responses to infectious pathogens. Microbiota composition is severely disrupted during sepsis, which has been linked to increased risk of mortality and secondary infections. However, efforts of using these microbes as a tool for prognostic or therapeutic purposes have been unsuccessful so far, and recent trials studying the impact of probiotics in critical illness did not improve patient outcomes. Despite these negative results, researchers must continue their attempts of harnessing the microbiome to improve sepsis survival in patients with a high risk of clinical deterioration. Promising research avenues that could potentially benefit sepsis patients include the development of next-generation probiotics, use of the microbiome as a theranostic tool to direct therapy, and addressing the restoration of microbial communities following ICU discharge.SummaryAlthough research focused on microbiome-mediated therapy in critically ill patients has not yielded the results that were anticipated, we should not abandon our efforts to translate promising preclinical findings into clinical practice.

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“…Acute kidney injury (AKI) is a common complication of sepsis, and sepsis-associated AKI (SA-AKI) increases the risk of patient mortality (Peng et al, 2014). Existing research suggests that the gut microbiota is involved in the occurrence and progression of SA-AKI (Zhang et al, 2018;Chavez-Iñiguez et al, 2022;Xu et al, 2022). Meijers et al proposed the concept of the "gut-kidney axis" in 2011; subsequently, Pahl et al refined the theory (Meijers and Evenepoel, 2011;Pahl and Vaziri, 2015).…”

Section: Introductionmentioning

confidence: 99%

Investigating gut microbiota–blood and urine metabolite correlations in early sepsis-induced acute kidney injury: insights from targeted KEGG analyses

Xu,

Zhu

et al. 2024

Front. Cell. Infect. Microbiol.

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BackgroundThe interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI.MethodsUtilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns.ResultsOur study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation.ConclusionsSignificant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.

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Contribution of gut microbiota toward renal function in sepsis

Cited by 9 publications

References 117 publications

Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism

Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism

Leveraging the microbiome in the treatment of sepsis: potential pitfalls and new perspectives

Investigating gut microbiota–blood and urine metabolite correlations in early sepsis-induced acute kidney injury: insights from targeted KEGG analyses

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