Hypertension of liver-yang hyperactivity syndrome induced by a high salt diet by altering components of the gut microbiota associated with the glutamate/GABA-glutamine cycle.

The gut microbiota and metabolites are closely related to hypertension; however, the changes in the composition of the gut microbiome and metabolites linking a high salt diet to elevated blood pressure are not established. In this study, traditional Chinese medicine (TCM) syndrome of hypertension caused by high salt had been diagnosed and the pathogenesis of hypertension was explored from the perspective of intestinal microecology. Rats in a high salt diet-induced hypertension group (CG) and normal group (CZ) were compared by 16S rRNA gene full-length sequencing and liquid chromatography and mass spectrometry to identify differences in the bacterial community structure, metabolites, and metabolic pathways. Hypertension induced by a high salt diet belongs to liver-Yang hyperactivity syndrome. Alpha and beta diversity as well as the composition of microbiota from the phylum to species levels differed substantially between the CG and CZ groups. In an analysis of differential metabolites in the intestines, a high salt diet mainly affected the metabolism of amino acids and their derivatives; in particular, γ-aminobutyric acid (GABA) was down-regulated and glutamic acid and its derivatives were up-regulated under a high salt diet. Based on a KEGG analysis, high salt intake mainly altered pathways related to GABA and the glutamate/glutamine metabolism, such as the GABAergic synapse pathway and glutamatergic synapse pathway. The correlation analysis of differential gut microbes and differential metabolites suggested that a high salt diet promoted hypertension via the inhibition of Clostridiaceae_1 growth and alterations in the GABA metabolic pathway, leading to increased blood pressure. These findings suggest that a high salt diet induces hypertension of liver-Yang hyperactivity syndrome by mediating the microbiota associated with the glutamate/GABA-glutamine metabolic cycle via the gut-brain axis.

Bacterial Lactase Gene Characteristics in Intestinal Contents of Antibiotic-Associated Diarrhea Mice Treated with Debaryomyces hansenii.

BACKGROUND Debaryomyces hansenii exhibits a therapeutic effect on antibiotic-associated diarrhea (AAD) by promoting the growth of beneficial intestinal bacteria. Previous research has reported that AAD involves not only dysbacteriosis but also dysfunction of the activity of intestinal enzymes (such as lactase). Enzyme activities can be influenced by many other factors, such as gene expression. The present study showed that D. hansenii has a curative effect on AAD at the lactase gene level. MATERIAL AND METHODS The effect of D. hansenii on the lactase gene from intestinal bacteria in AAD mice was investigated. The diarrhea model was established with a gentamycin sulfate and cefradine capsule mixture. The antibiotic mixture (23.33 mL·kg⁻¹·day⁻¹) was intragastrically administered for 5 days. Subsequently, half of the diarrhea mice were treated with D. hansenii twice a day for 3 days while the other mice were intragastrically administered with the same volume of distilled water. Next, the intestinal contents were collected, and metagenomic DNA was extracted for high-throughput sequencing analysis. RESULTS The Chao1 and Shannon indices decreased significantly following treatment with D. hansenii (P<0.01 and P<0.05, respectively). Moreover, the clusters in the D. hansenii group mice were quite different from those in the normal group mice and model group mice. Following treatment with D. hansenii, the quantity of lactase genes in Enterobacter sp. 638 and Modestobacter increased markedly, and the richness of intestinal bacterial lactase genes in Fretibacterium recovered. CONCLUSIONS D. hansenii altered the lactase-producing bacterial community structure and promoted the growth of several critical lactase-producing bacteria, such as Enterobacter sp. 638 and Modestobacter.

Diversity of bacterial lactase genes in intestinal contents of mice with antibiotics-induced diarrhea.

AIM: To investigate the diversity of bacterial lactase genes in the intestinal contents of mice with antibiotics-induced diarrhea. METHODS: Following 2 d of adaptive feeding, 12 specific pathogen-free Kunming mice were randomly divided into the control group and model group. The mouse model of antibiotics-induced diarrhea was established by gastric perfusion with mixed antibiotics (23.33 mL·kg-1·d-1) composed of gentamicin sulfate and cephradine capsules administered for 5 days, and the control group was treated with an equal amount of sterile water. Contents of the jejunum and ileum were then collected and metagenomic DNA was extracted, after which analysis of bacterial lactase genes using operational taxonomic units (OTUs) was carried out after amplification and sequencing. RESULTS: OTUs were 871 and 963 in the model group and control group, respectively, and 690 of these were identical. There were significant differences in Chao1 and ACE indices between the two groups (P < 0.05). Principal component analysis, principal coordination analysis and nonmetric multidimensional scaling analyses showed that OTUs distribution in the control group was relatively intensive, and differences among individuals were small, while in the model group, they were widely dispersed and more diversified. Bacterial lactase genes from the intestinal contents of the control group were related to Proteobacteria, Actinobacteria, Firmicutes and unclassified bacteria. Of these, Proteobacteria was the most abundant phylum. In contrast, the bacterial population was less diverse and abundant in the model group, as the abundance of Bradyrhizobium sp. BTAi1, Agrobacterium sp. H13-3, Acidovorax sp. KKS102, Azoarcus sp. KH32C and Aeromonas caviae was lower than that in the control group. In addition, of the known species, the control group and model group had their own unique genera, respectively. CONCLUSION: Antibiotics reduce the diversity of bacterial lactase genes in the intestinal contents, decrease the abundance of lactase gene, change the lactase gene strains, and transform their structures.