Microbiome-gut-brain axis contributes to patients and Bama miniature pigs with acute large ischemic stroke.

Acute large hemispheric infarction (ALHI) is an overwhelming emergency with a great challenge of gastrointestinal dysfunction clinically. Here, we initially proposed delayed bowel movements as the clinical phenotype of strike to gut-brain axis (GBA) in ALHI patients by epidemiological analysis of 499 acute ischemic stroke (AIS) patients. 1H NMR-based metabolomics revealed that AIS markedly altered plasma global metabolic profiling of patients compared with healthy controls. Risk factors of strike on GBA were the National Institutes of Health Stroke Scale (NIHSS) score ≥ 5 and stroke onset time ≤ 24 h. As a result, first defecating time after admission to the hospital ≥2 days could be considered as a potential risk factor for strike on GBA. Subsequently, the ALHI Bama miniature (BM) pig model with acute symptomatic seizure was successfully established by ligation of the left ascending pharyngeal artery combined with local air injection. Clinical phenotypes of brain necrosis such as hemiplegia were examined with brain diffusion-weighted imaging (DWI) and pathological diagnosis. In addition to global brain injury and inflammation, we also found that ALHI induced marked alterations of intestinal barrier integrity, the gut microbial community, and microbiota-derived metabolites including serotonin and neurotransmitters in both plasma and multiple brain tissues of BM pigs. These findings revealed that microbiota-gut-brain axis highly contributed to the occurrence and development of ALHI.

Exploring plasma metabolomic changes in sepsis: a clinical matching study based on gas chromatography-mass spectrometry.

BACKGROUND: Sepsis is a deleterious systemic inflammatory response to infection, and despite advances in treatment, the mortality rate remains high. We hypothesized that plasma metabolism could clarify sepsis in patients complicated by organ dysfunction. METHODS: Plasma samples from 31 patients with sepsis and 23 healthy individuals of comparable age, gender, and body mass index (BMI) were collected. Plasma metabolites were detected through gas chromatography-mass spectrometry (GC-MS), and relevant metabolic pathways were predicted using the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway database. Student's t-test was employed for statistical analysis. In addition, to explore sepsis organ dysfunction, plasma samples of sepsis patients were further analyzed by metabolomics subgroup analysis according to organ dysfunction. RESULTS: A total of 222 metabolites were detected, which included 124 metabolites with statistical significance between the sepsis and control groups. Among these, we found 26 were fatty acids, including 3 branched fatty acids, 10 were saturated fatty acids, and 13 were unsaturated fatty acids that were found in sepsis plasma samples but not in the controls. In addition, 158 metabolic pathways were predicted, 74 of which were significant. Further subgroup analysis identified seven metabolites in acute kidney injury (AKI), three metabolites in acute respiratory distress syndrome (ARDS), seven metabolites in sepsis-induced myocardial dysfunction (SIMD), and four metabolites in acute hepatic ischemia (AHI) that were significantly different. The results showed that the sepsis samples exhibited extensive changes in amino acids, fatty acids, and tricarboxylic acid (TCA)-cycle products. In addition, three metabolic pathways-namely, energy metabolism, amino acid metabolism, and lipid metabolism-were downregulated in sepsis patients. CONCLUSIONS: The downregulated energy, amino acid, and lipid metabolism found in our study may serve as a novel clinical marker for the dysregulated internal environment, particularly involving energy metabolism, which results in sepsis.

Wulingsan (Oryeongsan/Goreisan) ameliorate lipid metabolism of obesity rats via regulation of the plasma metabolic profiling.

OBJECTIVES: Wulingsan has been used to cure disease about disorders related to fluid balance for thousands of years. The clinical practice of modern Chinese medicine has found that Wulingsan has the effect on reducing weight and fat, but its mechanism is not clear. This study investigated its effects on obesity rats and explored the underlying mechanisms by analyzing the plasma metabolic profiling. METHODS: The effects of Wulingsan on obesity were evaluated with obesity rats induced by high-fat diet. Ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers and evaluate whether Wulingsan could regulate these biomarkers. The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) in serum were assessed by ELISA kits. RESULTS: Remarkably, TG, TC, HDL-C and LDL-C in obesity rats were ameliorated after oral administration of Wulingsan. Further investigation indicated that the plasma metabolic profiles were clearly improved. Twelve potential biomarkers were identified. After intervention, these biomarkers turned back to normal level at some extent. CONCLUSION: The results showed that Wulingsan extract groups were normalized. Additionally, this study also showed that the metabonomics method was a promising tool to unravel how traditional Chinese medicines worked and these data can provide scientific basis for clinical application of Wulingsan.

Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling.

Malnutrition is a severe non-communicable disease, which is prevalent in children from low-income countries. Recently, a number of metagenomics studies have illustrated associations between the altered gut microbiota and child malnutrition. However, these studies did not examine metabolic functions and interactions between individual species in the gut microbiota during health and malnutrition. Here, we applied genome-scale metabolic modeling to model the gut microbial species, which were selected from healthy and malnourished children from three countries. Our analysis showed reduced metabolite production capabilities in children from two low-income countries compared with a high-income country. Additionally, the models were also used to predict the community-level metabolic potentials of gut microbes and the patterns of pairwise interactions among species. Hereby we found that due to bacterial interactions there may be reduced production of certain amino acids in malnourished children compared with healthy children from the same communities. To gain insight into alterations in the metabolism of malnourished (stunted) children, we also performed targeted plasma metabolic profiling in the first 2 years of life of 25 healthy and 25 stunted children. Plasma metabolic profiling further revealed that stunted children had reduced plasma levels of essential amino acids compared to healthy controls. Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition.