Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice.

Growing evidence has demonstrated that cold and humid environmental stress triggers gastrointestinal (GI) disorders. In this study, we explored the effects of intestinal microbiota homeostasis on the intestinal mucus barrier and GI disorders by cold and humid environmental stress. Moreover, the inner link between the intestinal mucosal microbiota and metabolites in mice with cold and humid environmental stress was interpreted by integrative analysis of PacBio HiFi sequencing microbial genomics and targeted metabolomics. In the current study, we found (1) after the cold and wet cold and humid environmental stress intervened in the intestinal microbiota disorder and homeostasis mice respectively, the bacterial culturing and fluorescein diacetate (FDA) microbial activity detection of intestinal microbiota including feces, intestinal contents, and intestinal mucosa suggested that the cold and humid environmental stress decreased the colony of culturable bacteria and microbial activity, in which intestinal microbiota disorder aggravated the injury of the intestinal mucus barrier and the GI symptoms related to cold and humid environmental stress; (2) the serum amino acid transferases such as glutamate pyruvic transa (GPT), and glutamic oxaloacetic transaminase (GOT) in cold and humid environmental stressed mice increased significantly, indicating that the intestinal microbiota adapted to cold and humid environmental stress by regulating the host's amino acid metabolism; (3) the integrative analysis of multi-omics illustrated a prediction model based on the microbiota Lactobacillus reuteri abundance and host amino acid level that can predict intestinal mucoprotein Muc2 with an adjusted R2 of 75.0%. In conclusion, the cold and humid environmental stress regulates the neurotransmitter amino acids metabolic function both in intestinal mucosal microbiota and host serum by adjusting the composition of the dominant bacterial population Lactobacillus reuteri, which contributes to the intestinal mucus barrier injury and GI disorders caused by cold and humid environmental stress.

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.

[Study on pharmacokinetics-pharmacodynamics correlation of yin teng gu bi kang prescription].

OBJECTIVE: To study pharmacokinetics-pharmacodynamics (PK-PD) correlation of Yin Teng Gu Bi Kang (YTGBK) prescription through determination of Tanshinone II(A) concentration and the level of Malondialdehyde (MDA) in plasma in normal and blood stasis rats treated with YTGBK prescription. METHODS: The concentration of Tanshinone II(A) in the plasma was measured by HPLC-UV and loratadine was used as internal standard; Thiobarbituric acid reactive substance assay (TBARS) was adopted to determine the concentration of MDA in the plasma Area under the concentration-time curve (AUC) and area under the effect-time curve (AUE) were calculated using linear trapezoid rule. The correlation and regression analysis was performed by plotting AUE (Y) versus lgAUC (X) using linear regression. RESULTS: YTGBK prescription could significantly decrease MDA level in the plasma in above two different physiological rats at the analyzed time point (P < 0.05). Scatter plots of AUE-lgAUC showed an upward trend. The results of the correlation and regression analysis were as follows: Y = 53.367 X -30.780, r = 0. 822, P = 0.007 for normal rats and Y = 61.091 X -39.863, r = 0.777, P = 0.003 for model rats, respectively. CONCLUSION: There is a positive correlation between Tanshinone II(A) level in plasma and the antioxidant activity of YTGBK prescription in decreasing MDA level, which indicates that Tanshinone II(A) is the antioxidant effective substance of YTGBK prescription.

[Comparison of pharmaceutical chemistry difference of effective parts from yin teng gu bi kang prescription in normal rats and rats with acute blood stasis].

OBJECTIVE: To elucidate the material basis of Yin Teng Gu Bi Kang Prescription (YTGBKP) for efficacy of promoting blood circulation by means of comparing the pharmaceutical chemistry difference of effective parts in normal rats and rats with acute blood stasis. METHODS: The pharmaceutical chemistry fingerprints of effective parts under physiological and pathological status (acute blood stasis) were established by HPLC,and the in vitro and in vivo chromatographic peaks were compared and analyzed. RESULTS: Five batches of drug-containing plasma samples had 14 chromatographic peaks under normal physiological status,among which 3 rooted in plasma, 9 existed originally in YTGBKP,2 were metabolites. The compound with retention lime at 12 min was identified as ferulic acid by comparing with reference standard; While under pathological status (acute blood stasis), five batches of the drug-containing plasma samples had 14 chromatographic peaks, among which 3 rooted in plasma, 9 existed originally in YTGBKP, 2 were metabolites. The compounds with retention time at 12 min and 32 min were identified as ferulic acid and icariin respectively by comparing with reference standards. There were 10 common peaks under normal physiological and pathological status (acute bloodl stasis) excluding peaks in blank plasma. The intensity of the common peaks produced under pathological status was stronger than that under normal physiological status significantly; Variance analysis showed that there were significant differences (P < 0.05) in peak areas of 3 peaks. CONCLUSION: Blood stasis has influence on the absorption and metabolism of most ingredients from YTGBKPi; Prototypes and metabolites may be the effective substance on promoting blood circulation.