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Updated: Jun 26, 2025
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice
Hongchao Wang1,2, Yuan He1,2, Danting Dang1,2
1State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.
Abstract:
Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.
Insights
Tryptophan metabolites from gut bacteria can reduce allergic asthma symptoms in mice. These compounds, particularly indole-3-carbaldehyde (I3C), improve survival and decrease inflammation by modulating the gut microbiota and its metabolic pathways.
Area of Science:
- Immunology
- Microbiology
- Metabolomics
Background:
- Asthma is a widespread respiratory condition characterized by airway inflammation.
- The gut microbiota plays a crucial role in immune system regulation and has been implicated in allergic diseases.
- Tryptophan metabolites, produced by gut bacteria, are increasingly recognized for their immunomodulatory effects.
Purpose of the Study:
- To investigate whether gut microbiota-derived tryptophan metabolites can alleviate allergic asthma inflammation in a mouse model.
- To explore the specific effects of kynurenine (KYN), indole-3-lactic acid (ILA), indole-3-carbaldehyde (I3C), and indole acetic acid (IAA) on asthma.
- To elucidate the underlying mechanisms involving gut microbiota composition and tryptophan metabolism.
Main Methods:
- An ovalbumin (OVA)-induced allergic asthma mouse model was established.
- Mice were treated with four specific tryptophan metabolites (KYN, ILA, I3C, IAA) via intraperitoneal injection.
- Evaluated outcomes included survival, weight, asthma symptom scores, serum IgE levels, bronchoalveolar lavage fluid (BALF) cytokines, gut microbiota composition (16S rRNA sequencing), and fecal targeted metabolomics.
Main Results:
- All four tested tryptophan metabolites improved survival, weight, and asthma symptoms, and reduced lung inflammatory cells, with I3C showing the most significant effects.
- I3C and IAA markedly reduced OVA-specific IgE and inflammatory cytokine levels.
- KYN restored gut microbiota diversity, while I3C, KYN, and ILA altered the abundance of specific bacterial genera (Anaeroplasma, Akkermansia, Ruminococcus_1). IAA enhanced overall gut microbial tryptophan metabolism.
Conclusions:
- Tryptophan metabolites demonstrate therapeutic potential in alleviating allergic asthma in mice.
- These metabolites may exert their effects by modulating the gut microbiota composition and enhancing tryptophan metabolic pathways.
- Findings suggest a promising role for targeting gut microbiota-derived tryptophan metabolites in clinical asthma management.
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