The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential

Zhang, Xue; Liu, Hong; Hashimoto, Kenji; Yuan, Shiying; Zhang, Jiancheng

doi:10.1186/s13054-022-04090-1

Cited by 50 publications

(28 citation statements)

References 171 publications

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“…The levels of butyric acid were decreased in critical patients, which was closely related to the reduction in butyrate-producing bacteria in septic patients (10). Because of the protective role of butyric acid in intestinal integrity, immune responses, liver injury, and brain injury (28–30), the lower abundance of butyrate-producing bacteria might be a risk factor for sepsis onset (10). In the current study, we observed decreasing trends in fecal SCFAs from septic patients over 3 weeks upon ICU admission.…”

Section: Discussionmentioning

confidence: 99%

Global Signatures of the Microbiome and Metabolome During Hospitalization of Septic Patients

Long

Zhang

et al. 2023

Shock

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Background: The gut plays an important role in the development of sepsis and acts as one of the possible drivers of multiple-organ dysfunction syndrome. This study aimed to explore the dynamic alterations in the gut microbiota and its metabolites in septic patients at different stages of intensive care unit (ICU) admission. Methods: In this prospective observational study, a total of 109 fecal samples from 23 septic patients, 16 nonseptic ICU patients and 10 healthy controls were analyzed. 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry targeted metabolomics were used for microbiota and metabolome analysis. A prediction model combining the Sequential Organ Failure Assessment score, Klebsiella, taurocholic acid, and butyric acid was used to predict the prognosis of sepsis. Results: The diversity and dominant species of the gut microbiota of septic patients were significantly disturbed. The proportions of normal gut microbiota, such as Firmicutes on the phylum level, as well as Faecalibacterium, Subdoligranulum, Ruminococcus, Agathobacter, and Blautia on the genus level, were decreased at different stages of ICU admission, while the proportions of potential pathogenic bacteria, such as Proteobacteria on the phylum level, and Enterococcus and Stenotrophomonas on the genus level were significantly increased. In addition, the amount of short-chain fatty acids and secondary bile acids decreased in septic patients, while that of the primary bile acids increased markedly. Bacterial richness and diversity were lower in the nonsurviving patients than those in the surviving patients in the later stage of ICU admission. In the nomogram model, the higher abundance of Klebsiella, concentration of taurocholic acid, and Sequential Organ Failure Assessment score, combined with a lower butyric acid concentration, could predict a higher probability of death from sepsis. Conclusions: Our study indicated that the dynamical alterations of gut microbiota and its metabolites were associated with the prognosis of the sepsis. Based on these alterations and clinical indicators, a nomogram model to predict the prognosis of septic patients was performed.

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Section: Discussionmentioning

confidence: 99%

Global Signatures of the Microbiome and Metabolome During Hospitalization of Septic Patients

Long

Zhang

et al. 2023

Shock

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“…Clinical study has found that gut microbiota is associated with 28-day mortality among critically ill patients [22]. Given the interactions with various organs, the gut dysbiosis and compromised intestinal barrier integrity deeply participate in the development and exacerbation of critical illness [23][24][25]. Since the gut dysbiosis has profound effects on the development, maintenance, and outcomes of sepsis [26], the different performances of D-lactate, LPS and DAO in our study can be explained that even under similar challenges from IECs damage, patients with gut dysbiosis are more susceptible to compromised intestinal barrier integrity, bacterial translocation and sepsis, and subsequent worse outcome.…”

Section: The Effect Of Compromised Intestinal Barrier Integrity On Di...mentioning

confidence: 99%

Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?

Wang

Liang

Liu

et al. 2022

Diabetol Metab Syndr

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Background Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia. Methods This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups. Results A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group. Conclusions Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia.

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“…During critical illness, gastrointestinal transit changes, as well as unique medication and nutrition patterns, can drive dramatic changes in the gut microbiota [ 1 ]. Conversely, a disturbed microbiome provides a niche for the growth of pathogenic microbes, whose components can translocate across an impaired gut barrier and worsen the condition [ 4 ]. Although previous studies have focused on the microbial features of patients with sepsis, the role of bacteria found to be altered in sepsis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis

et al. 2023

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Background The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. Method In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. Results Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. Conclusion Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

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The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential

Cited by 50 publications

References 171 publications

Global Signatures of the Microbiome and Metabolome During Hospitalization of Septic Patients

Global Signatures of the Microbiome and Metabolome During Hospitalization of Septic Patients

Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis

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