Abstract
Mild micro-hepatic encephalopathy (MHE) is a severe complication of cirrhosis. At present, there are differences in the consistency of detection strategies and treatment directions for MHE. The characteristic changes in intestinal microbiota and serum metabolites in MHE patients and the possible relevant interaction mechanisms would inevitably affect the developmental direction of MHE. Therefore, the changes in the characteristics of intestinal microbiota and serum metabolites of MHE patients were determined, and the possible interactions between them were analyzed. Stool and serum tests were performed on both the MHE patients and healthy individuals. The 16S rRNA gene high-throughput sequencing and bioinformatics analyses were used to analyze the differences in intestinal microbiota in MHE patients. The serum metabolites were detected using liquid LC-MS/MS (liquid chromatography-mass spectrometry) technology, and the differences in the metabolic networks of blood metabolites in MHE patients were analyzed. A comprehensive bioinformatics analysis approach was adopted to identify the composition and characteristics of microbiota and serum metabolites and the possible correlation between them. The main characteristics of the structural imbalance in the intestinal microbiota of MHE patients included a decrease in the number of beneficial bacteria at the levels of phylum, class, order, family, and genus and an increase in the pathogenic bacteria, resulting in substantial changes in the relative abundances of bacteria in the intestinal microbiota. The main predicted functions that showed significant differences included chromosome, amino acid-related enzymes, methane metabolism, and arginine and proline metabolism. The detection of serum metabolites resulted in 10 different metabolites, including taurocholic acid, citrulline, d-phenyl-lactic acid, l-tyrosine, benzoate, phenylalanine, linoleic acid, eicosapedienic acid, alpha-dimorphecolic acid, and dehydroepiandrosterone. The subsequent metabolite pathways analysis showed differences in the metabolism of linoleic acid, phenyl-propane, caffeine, arginine, proline, glycine, serine, threonine, tyrosine, and pyrimidine compared to the control group. In summary, it seems that the changes in the microbiome that we have identified have resulted in corresponding changes to the serum metabolome. In turn, this may represent changes in the absorption of metabolites from the gut or reflect the changed metabolic capacity of the MHE liver or both. There were characteristic changes in the intestinal microbiota and serum metabolites in the MHE patients. There might be a related interaction mechanism between the two, which would provide evidence and direction for the detection and treatment strategies of MHE.
Highlights
Micro-hepatic encephalopathy (MHE) is a particular type of hepatic encephalopathy (HE), with usually no apparent signs and symptoms
Recent studies have found that cirrhosis is associated with changes in the composition and function of intestinal microbiota, which might accelerate the progression of multiple complications, including infections, such as MHE, spontaneous bacterial peritonitis (SBP), and renal dysfunction [4,5]
The original data were transformed into CDF format file by cdfbridge in masslynx 4.1 workstation software, and the xcms package was used for peak extraction, peak comparison, peak filtering, supplement of missing peaks and other data processing
Summary
Micro-hepatic encephalopathy (MHE) is a particular type of hepatic encephalopathy (HE), with usually no apparent signs and symptoms. Ammonia poisoning, caused by the disordered metabolism of ammonia, can trigger the cascade reaction of neuron apoptosis [3]. Both the MHE and dominant HE have different degrees of cognitive dysfunction but their. Literature evidence shows that the intestinal microbiota can directly affect the blood–brain barrier, myelin sheath, neurogenesis, maturation of microglial cells, and other basic neural development processes, regulating a variety of neurophysiological activities [7]. It forms tryptamine, an arylamine neurotransmitter, which affects the acquisition of amino acids used in the synthesis of neuroactive peptides. Starting from intestinal microbiota and serum metabolites, this study investigated the correlation between the structure, function, and metabolism of different bacteria with MHE and the characteristic serum metabolites and metabolic pathways
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