ABSTRACT
Objective@#To explore the microbial correlation between oral tongue coating (TC) and gastric mucosa (GM) in patients with gastric intestinal metaplasia (GIM).@*Methods@#The present study recruited 1360 volunteers for upper gastrointestinal cancer screening. The microbiota in TC and GM were profiled by long-read sequencing of full-length 16S rRNA gene. The microbial diversity, community structure, and linear discriminant analysis effect size (LEfSe) were analyzed by the software Visual Genomics. SparCC correlation analysis was used to construct the commensal network and the graphical display was conducted by R software.@*Results@#The population included 44 patients with precancerous GIM, and 28 matched controls with negative rapid urease test (RUT) and non-symptomatic chronic superficial gastritis (CSG). No significant difference in diversity was observed between GIM patients and controls in TC or GM microbiota (P > 0.05). Patients had a higher percentage of 41 – 60 co-occurring operational taxonomic units (OTUs) between TC and GM than controls (34.1% vs. 25.0%) (P < 0.05). The LEfSe showed that TC Prevotella melaninogenica and three gastric Helicobacter species (i.e., Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) were enriched in patients with GIM. Furthermore, GIM patients with positive RUT had a lower percentage of co-occurring OTUs over 20 (P < 0.05), and lower abundances of gastric Veillonella, Pseudonocardia, and Mesorhizobium than those with negative RUT (P < 0.05). The commensal network between TC and GM was more complex in GIM patients than in controls. GIM patients with positive RUT demonstrated more bacterial correlations between TC and GM than those with negative RUT. Finally, the serum ratio of PG-I/II was negatively correlated with three gastric Helicobacter species (Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) in patients with negative RUT (P < 0.05), and negatively correlated with two TC species (Fusobacterium nucleatum subsp. nucleatum and Campylobacter showae) in patients with positive RUT (P < 0.05).@*Conclusion@#The development of GIM potentiated the commensal network between oral TC and GM, providing microbial evidence of the correlation between TC and the stomach.
ABSTRACT
This study investigated the modulatory effect of synthetic cannbinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-Hr3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique.The results showed that:(!) The majority of examined neurons (78.70％) were sensitive to 5-HT (3-300 μmol/L).5-HT induced inward currents in a concentrationdependent manner and the currents were blocked by ICS 205-930 (1 μmol/L),a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01-1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners.The concentration-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value.The EC50values of two curves were very close (17.5±4.5) μmol/L vs.(15.2±4.5) μmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HI3 by (48.65±4.15)％; (3) Neither AM281,a selective CBI receptor antagonist,nor AM630,a selective CB2 receptor antagonist reversed the inhibition of I5-HT3by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application,inhibitory effect was gradually increased and the maximal inhibition took place at 90 s,and the inhibition remained at the same level after 90 s.We are led to concluded thatWIN55,212-2 inhibited I5-Hr3 significantly and neither CB1 receptor antagonist nor CB2 receptor antagonist could reverse the inhibition of I5-HT3 by WIN55,212-2.Moreover,WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor.WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner.The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2,but the mechanism by which WIN55,212-2 inhibits I5-HT3 warrants further investigation.