Herba Patriniae with probiotics targets Escherichia fergusonii and the 5-hydroxytryptophan-trimethylamine N-oxide axis in Parkinson's disease.

The Bacteroidaceae enterotype (ET-B) was identified as a high-risk enterotype for Parkinson's disease using public metagenomic data.

• Public metagenomic data from PD patients and healthy controls (HC) were analyzed to characterize enterotypes.
• ET-B was characterized by enrichment of Escherichia fergusonii compared to other enterotypes.
• Different enterotypes showed distinct gut microbiota and microbial metabolite profiles associated with PD susceptibility.

Escherichia fergusonii was associated with consumption of neuroprotective 5-hydroxytryptophan (5-HTP) and production of pro-inflammatory trimethylamine N-oxide (TMAO).

• E. fergusonii was enriched in the high-risk Bacteroidaceae enterotype.
• The bacterium was implicated in a 5-HTP-TMAO metabolic axis potentially linked to PD risk.
• The pathogenic role of E. fergusonii was validated using an in vitro gut-brain axis (GBA) model established by co-culturing PC12 neuronal cells and Caco-2 intestinal epithelial cells.

The F.l-HP combination therapy (Faecalibacterium prausnitzii, Lactiplantibacillus plantarum, and Herba Patriniae extract) significantly suppressed the growth of E. fergusonii while promoting the proliferation of beneficial probiotics.

• F.l-HP combined Patrinia scabiosaefolia Fisch (Herba Patriniae; HP) extract with probiotics F. prausnitzii and L. plantarum.
• The intervention was assessed on bacterial growth, key metabolites (5-HTP, TMAO, butyrate), neuroinflammation, oxidative stress, mitochondrial function, and gut barrier integrity.
• Suppression of E. fergusonii growth was accompanied by increased proliferation of the beneficial probiotic strains.

F.l-HP treatment restored metabolic balance by reducing 5-HTP consumption and TMAO production while increasing butyrate levels.

• The intervention reduced the consumption of neuroprotective 5-HTP associated with E. fergusonii activity.
• TMAO production, which is pro-inflammatory, was decreased following F.l-HP treatment.
• Butyrate levels were increased, consistent with a shift toward a more beneficial gut microbial metabolite profile.

F.l-HP treatment alleviated neuroinflammation and oxidative stress in neuronal cells and restored mitochondrial function via the p-Akt pathway.

• Effects were assessed in PC12 neuronal cells as part of the in vitro gut-brain axis model.
• Neuroinflammation and oxidative stress markers were reduced following F.l-HP intervention.
• Mitochondrial function restoration was mediated through activation of the p-Akt signaling pathway.

F.l-HP treatment enhanced gut barrier integrity in intestinal cells by upregulating zonula occludens-1 (ZO-1) expression and activating p-AMPKα signaling.

• Effects were assessed in Caco-2 intestinal epithelial cells.
• Zonula occludens-1 (ZO-1), a tight junction protein, was upregulated following F.l-HP treatment.
• Gut barrier integrity enhancement was associated with activation of the p-AMPKα signaling pathway.
• This finding suggests a mechanism by which F.l-HP may protect the intestinal barrier in the context of PD-related gut dysfunction.