Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management

Xiaoang Li; Imran Khan; Ruixuan Han; Guoxin Huang; Wenrui Xia; Lin Yin; Wai Kit Leong; Lu Su; Betty Yuen-Kwan Law; Vincent Kam Wai Wong; Qiang Wu; Xiaoling Guo; W L Wendy Hsiao

doi:10.1016/j.phymed.2024.156101

Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management

Phytomedicine. 2024 Sep 30:135:156101. doi: 10.1016/j.phymed.2024.156101. Online ahead of print.

Authors

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
² Foshan Maternal and Child Health Research Institute, Foshan Women and Children's Hospital Affiliated to Southern Medical University, Foshan, China.
³ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Foshan Maternal and Child Health Research Institute, Foshan Women and Children's Hospital Affiliated to Southern Medical University, Foshan, China. Electronic address: bowhsiao@gamil.com.

PMID: 39522254
DOI: 10.1016/j.phymed.2024.156101

Abstract

Background: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

Purpose: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

Methods: To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

Results: GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

Conclusion: To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.

Keywords: Clostridium; Gut dysbiosis; Gynostemma pentaphyllum saponins; Lactobacillus; Parabacteroides distasonis; Peanut allergy.