Anwei decoction alleviates chronic atrophic gastritis by modulating the gut microbiota-metabolite axis and NLRP3 inflammasome activity.

AWD demonstrated an overall effective rate of 82.5% in a multicenter cohort study of CAG patients.

• The multicenter cohort study showed statistically significant results (P < 0.01)
• The overall effective rate was 82.5% for clinical symptom improvement
• This clinical finding motivated the mechanistic investigation of AWD against CAG

AWD significantly reduced serum levels of pro-inflammatory cytokines in the CAG rat model.

• AWD reduced serum levels of IL-1β, IL-18, tumor necrosis factor-α, and lipopolysaccharide
• All reductions demonstrated significant statistical differences (all P < 0.01)
• Cytokine concentrations were determined by enzyme-linked immunosorbent assay
• The CAG rat model was established using N-methyl-N'-nitro-N-nitrosoguanidine

AWD substantially inhibited NLRP3 inflammasome signaling at both the mRNA and protein levels in gastric mucosal tissue.

• AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue (P < 0.01)
• AWD concurrently decreased protein abundance of NLRP3, IL-1β, and caspase-1 (all P < 0.01)
• mRNA levels were measured by quantitative real-time polymerase chain reaction
• Protein expression was detected by Western blotting
• These findings indicate suppression of inflammasome signaling activation

AWD intervention significantly increased the relative abundance of beneficial gut bacteria in CAG rats.

• Gut microbiota structural alterations were analyzed using high-throughput 16S rRNA sequencing
• AWD increased the relative abundance of beneficial bacteria
• Associated microbial metabolites were identified as likely inhibitors of the NLRP3 inflammasome pathway
• The mechanism was proposed to occur through modulation of immune cell function

Non-targeted metabolomics revealed that AWD exerts anti-inflammatory effects by regulating multiple critical metabolic pathways.

• Metabolomics analysis was performed using liquid chromatography-mass spectrometry based untargeted metabolomics
• Regulated pathways included the Kaposi's sarcoma-associated herpesvirus infection pathway, autophagy processes, and glycosylphosphatidylinositol-anchor biosynthesis
• Serum-derived constituents transferred from AWD were identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry
• The integrated approach combined 16S rRNA sequencing and metabolomics to characterize multi-target therapeutic mechanisms

AWD remodels intestinal microbiota-metabolite homeostasis and enhances intestinal barrier function alongside its direct anti-inflammatory effects.

• AWD was found to operate through dual mechanisms: direct suppression of gastric mucosal inflammation and remodeling of intestinal microbiota-metabolite homeostasis
• AWD enhanced intestinal barrier function and regulated mucosal immune responses
• The gut microbiota-metabolite axis was identified as a key therapeutic target of AWD
• The integrated gut microbiota and metabolomics approach systematically clarified AWD's multi-target therapeutic mechanisms against CAG