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

Critical Care, Journal Year: 2023, Volume and Issue: 27(1)

Published: March 28, 2023

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

Language: Английский

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Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 11, 2023

Objective Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role pathophysiology sepsis. Antibiotic therapy can reduce a patient’s commensal bacterial population and raise their risk developing subsequent illnesses, where gut microbiota dysbiosis may be key factor. Methods In this study, we analyzed 16S rRNA fecal samples from both healthy people patients with sepsis determine if alterations bacteria are associated Then, developed mouse model using cecal ligation puncture (CLP) order examine effects transplantation (FMT) short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, microbiota, mucosal barrier function. Results patients’ composition significantly differed that people. At phylum level, amount Proteobacteria intestinal flora was much larger than control group, whereas number Firmicutes lower. Mice disorders (ANC group) were found have elevated death, inflammation, organ failure as compared CLP mice. However, all these could reversed by FMT SCFAs. SCFAs regulate abundance such Firmicutes, Proteobacteria, Escherichia Shigella, Lactobacillus, restoring them levels comparable those addition, they increased expression Occludin protein colon mice sepsis, downregulated NLRP3 GSDMD-N proteins, reduced release factors IL-1β IL-18 inhibit cell pyroptosis, ultimately playing protective Disccusion provide microbe-related benefit suggesting viable treatment for

Language: Английский

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Recent Advances in Gut‐ and Gut–Organ‐Axis‐on‐a‐Chip Models

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: Jan. 20, 2024

The human gut extracts nutrients from the diet while forming largest barrier against outer environment. In addition, actively maintains homeostasis through intricate interactions with microbes, immune system, enteric nervous and other organs. These influence digestive health and, furthermore, play crucial roles in systemic disease. Given its primary role absorbing metabolizing orally administered drugs, there is significant interest development of preclinical vitro model systems that can accurately emulate intestine vivo. A gut-on-a-chip system holds great potential as a testing screening platform because ability to physiological aspects vivo tissues expandability incorporate combine This review aims identify key features need be incorporated build more accurate models highlights recent progress competing technologies toward building physiologically relevant systems. Furthermore, various efforts construct multi-organ gut, called gut-organ-axis-on-a-chip models, are discussed. relevance provide valuable platforms for bridging gap between clinical studies.

Language: Английский

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Approach to the diagnosis and management of dysbiosis

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: April 19, 2024

All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered microbiome. The number of bacteria almost equal human cells, however, the genome these may be 100 times larger than genome. Every aspect physiology health can influenced by microbiome living in various parts our body. Any imbalance composition or function is seen as dysbiosis. Different types dysbiosis corresponding symptoms depend on site microbial imbalance. contribution intestinal extra-intestinal microbiota to influence systemic activities through interplay between different axes. Whole body complex process involving gut non-gut related It still at stage infancy has not yet been fully understood. Dysbiosis genetic factors, lifestyle habits, diet including ultra-processed foods food additives, well medications. associated with many diseases cannot diagnosed standard blood tests investigations. Microbiota derived metabolites analyzed useful management addressed altering proper modulation. effect interventions humans depends beneficial alteration mostly based animal studies evolving evidence from studies. There tremendous potential for diagnosis, treatment, prognosis diseases, as, monitoring disease humans. system-based approach diagnosis better pure taxonomic approach. could new therapeutic target conditions.

Language: Английский

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Sublethal systemic LPS in mice enables gut-luminal pathogens to bloom through oxygen species-mediated microbiota inhibition

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

Published: March 20, 2025

Abstract Endotoxin-driven systemic immune activation is a common hallmark across various clinical conditions. During acute critical illness, elevated plasma lipopolysaccharide triggers non-specific activation. In addition, compositional shift in the gut microbiota, including an increase gut-luminal opportunistic pathogens, observed. Whether causal link exists between endotoxemia and abundance of pathogens incompletely understood. Here, we model acute, pathophysiological concentrations mice show that exposure promotes 100–10’000-fold expansion Klebsiella pneumoniae , Escherichia coli Enterococcus faecium Salmonella Typhimurium within one day, without overt enteropathy. Mechanistically, this driven by Toll-like receptor 4-dependent oxygen species levels, which transiently halts microbiota fermentation fuels growth facultative anaerobic through oxidative respiration. Thus, perturbs homeostasis favours potentially increasing risk infection critically ill patients.

Language: Английский

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Crosstalk Between the Nervous System and Systemic Organs in Acute Brain Injury

Neurocritical Care, Journal Year: 2023, Volume and Issue: 40(1), P. 337 - 348

Published: April 20, 2023

Language: Английский

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Lower gut dysbiosis and mortality in acute critical illness: a systematic review and meta-analysis

Intensive Care Medicine Experimental, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 3, 2023

Abstract Background The human gastrointestinal tract harbours a complex multi-kingdom community known as the microbiome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness yet clinical implications are unresolved. review systematically evaluates association between gut dysbiosis outcomes of patients early illness. Methods Following PRISMA guidelines, prospectively registered search was undertaken MEDLINE Cochrane databases for observational studies undertaking metagenomic sequencing lower critically ill adults children within 72 h admission. Eligible reported an alpha diversity metric one or more primary outcome, in-hospital mortality, secondary outcomes. After aggregate data were requested, meta-analysis performed four with mortality stratified high low Shannon index. Results identified 26 systematic 4 had suitable meta-analysis. No effect seen on after binary transformation index (odds ratio 0.52, CI 0.12–4.98, I 2 = 0.64) however certainty evidence low. Pathogen dominance commensal depletion each frequently associated adverse ecological sequelae, particularly overabundance Enterococcus . Conclusions There paucity large, rigorous this population. Globally, dynamically reduced ICU admission not mortality. abundance taxa such spp. appears offer greater predictive capacity important

Language: Английский

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Nutritional and metabolic modulation of inflammation in critically ill patients: a narrative review of rationale, evidence and grey areas

Annals of Intensive Care, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 1, 2024

Abstract Background Inflammation is the hallmark of critical illness and triggers neuro-endocrine stress response an oxidative stress. Acute inflammation initially essential for patient’s survival. However, ongoing or exaggerated inflammation, due to persistent organ dysfunction, immune dysfunction poor resolution, associated subsequent hypermetabolism hypercatabolism that severely impact short long-term functional status, autonomy, as well health-related costs. Modulation thus tempting, with goal improve short- outcomes critically ill patients. Findings can be modulated by nutritional strategies (including timing enteral nutrition initiation, provision some specific macronutrients micronutrients, use probiotics) metabolic treatments. The most interesting seem n-3 polyunsaturated fatty acids, vitamin D, antioxidant micronutrients propranolol, given their safety, accessibility clinical use, benefits in studies context care. optimal doses, route administration are still unknown them. Furthermore, recovery phase not studied defined. Conclusion rationale modulation obvious, based on pathophysiology increasingly described effects pharmacological strategies. Regretfully, there isn’t always substantial proof from research regarding positive impacts directly brought about modulation. Some arguments come performed severe burn patients, but such results should transposed non-burn patients caution. Further needed explore how after a illness.

Language: Английский

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Characterization of Gut Microbiota Composition in Type 2 Diabetes Patients: A Population-Based Study

International Journal of Environmental Research and Public Health, Journal Year: 2022, Volume and Issue: 19(23), P. 15913 - 15913

Published: Nov. 29, 2022

(1) Background: A clinical laboratory index to assess gut dysbiosis is the F/B ratio < 0.8. In fact, an elevated proportion of Firmicutes and a reduced population Bacteroides in diabetes type 2 (T2D) subjects has been observed. This study aimed detail status Italian population, focusing on some pathogenic spectra or metabolic disorders. (2) Material methods: quantity 334 fecal samples was analyzed order perform genetic testing sequencing. (3) Results: trend over imbalance observed percentage Proteobacteria (median value: 6.75%; interquartile range (IQR): 3.57−17.29%). statistically significant association (χ2p = 0.033) between T2D, corresponding Odds Ratio (OR) 1.86. It noted that females with cystitis/candidiasis are significantly prevalent T2D patients (p 0.01; OR: 3.59; 95% CI: 1.43−8.99). Although, non-diabetic males, sugar craving associated rate males 0.05; OR 1.07; CI 1.00−1.16). (4) Conclusion: patients, Bacteroidetes/Firmicutes biased favor Proteobacteria, be expected due nutritional habits patients. Thus, had altered permeability favoring development infections vaginal tract.

Language: Английский

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Structure-function relationship and impact on the gut-immune barrier function of non-digestible carbohydrates and human milk oligosaccharides applicable for infant formula

Critical Reviews in Food Science and Nutrition, Journal Year: 2023, Volume and Issue: 64(23), P. 8325 - 8345

Published: April 10, 2023

Human milk oligosaccharides (hMOs) in mothers' play a crucial role guiding the colonization of microbiota and gut-immune barrier development infants. Non-digestible carbohydrates (NDCs) such as synthetic single hMOs, galacto-oligosaccharides (GOS), inulin-type fructans pectin oligomers have been added to infant formula substitute some hMOs' functions. HMOs NDCs can modulate barrier, which is multiple-layered functional unit consisting microbiota, mucus layer, gut epithelium, immune system. There increasing evidence that structures complex polysaccharides may influence their efficacy modulating barrier. This review focuses on different individual hMOs commonly applied formulas (i) direct regulation microbiota-independent manner (ii) modulation composition microbial metabolites these microbiota-dependent manner. Both shown be essential for an adequate but effects are very dependent structural features hMO or NDC. knowledge might lead tailored specific target groups.

Language: Английский

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