Gut microbiota alters the Th1/Th2 balance and aggravates food-allergic enteropathy in a mouse model
Abstract
In non-IgE-mediated food allergy, food protein-induced enteropathy (FPE) can be evoked by the Th2 response. Some reports show that either Th2-biased immune responses or gut microbial dysbiosis can exacerbate food-allergic gastrointestinal inflammation. Nevertheless, it remains unclear whether gut microbiota directly affect Th2-biased immune responses involving FPE. To address this issue, we used OVA23-3 × BALB/cA mice, which is an FPE-like model. Feeding the mice an egg-white diet (EW) induced excessive Th2-type immune responses in CD4⁺ T cells in the mesenteric lymph nodes (MLNs), resulting in weight loss and enteropathy. Firstly, we compared specific pathogen-free (SPF) OVA23-3 × BALB/cA mice with germ-free (GF) OVA23-3 × BALB/cA mice when fed an EW diet. Symptoms shown in SPF mice were attenuated in GF mice, suggesting that gut microbiota may contribute to exacerbating symptoms. Additionally, we orally administered broad-spectrum antibiotics (Abx) to OVA23-3×BALB/cA mice and analyzed the gut microbiota. Compared with a no-Abx administration group, we found that Abx administration significantly altered the alpha and beta diversity of the gut microbiota in EW-fed mice. The presence of Alloprevotella, Bacteroides, and Muribaculaceae was reduced to approximately 10%. Both weight loss and enteropathy in EW-fed mice were ameliorated after Abx administration. Furthermore, administration of Abx to the EW-fed group improved the Th1/Th2 balance in MLN cells and decreased the mRNA expression of IL-33 and the aryl hydrocarbon receptor in the jejunum. These results suggest that some members of the gut microbiota disturb Th1/Th2 responses in the MLN, by affecting the small intestinal epithelium, thereby exacerbating Th2-biased responses and inducing food-allergic enteropathy.
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BibTeX
@article{nishitsuji2026microbiota,
title = {{Gut microbiota alters the Th1/Th2 balance and aggravates food-allergic enteropathy in a mouse model}},
author = {Kosuke NISHITSUJI and Tomohiro HOSHINO and Masato TSUDA and Yoshiyo BAMBA and Shigeru KAKUTA and Hiroyuki ADACHI and Naoki SHIMOJO and Huijuan JIA and Akira HOSONO and Kazuhiro HIRAYAMA and Satoshi HACHIMURA and Haruyo NAKAJIMA-ADACHI},
journal = {Bioscience of Microbiota, Food and Health},
year = {2026},
month = oct,
doi = {10.12938/bmfh.2025-106},
url = {https://www.jstage.jst.go.jp/article/bmfh/45/4/45_2025-106/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gut microbiota alters the Th1/Th2 balance and aggravates food-allergic enteropathy in a mouse model
AU - Kosuke NISHITSUJI
AU - Tomohiro HOSHINO
AU - Masato TSUDA
AU - Yoshiyo BAMBA
AU - Shigeru KAKUTA
AU - Hiroyuki ADACHI
AU - Naoki SHIMOJO
AU - Huijuan JIA
AU - Akira HOSONO
AU - Kazuhiro HIRAYAMA
AU - Satoshi HACHIMURA
AU - Haruyo NAKAJIMA-ADACHI
PY - 2026
DA - 2026/10/08
JO - Bioscience of Microbiota, Food and Health
DO - 10.12938/bmfh.2025-106
UR - https://www.jstage.jst.go.jp/article/bmfh/45/4/45_2025-106/_article
AB - In non-IgE-mediated food allergy, food protein-induced enteropathy (FPE) can be evoked by the Th2 response. Some reports show that either Th2-biased immune responses or gut microbial dysbiosis can exacerbate food-allergic gastrointestinal inflammation. Nevertheless, it remains unclear whether gut microbiota directly affect Th2-biased immune responses involving FPE. To address this issue, we used OVA23-3 × BALB/cA mice, which is an FPE-like model. Feeding the mice an egg-white diet (EW) induced excessive Th2-type immune responses in CD4⁺ T cells in the mesenteric lymph nodes (MLNs), resulting in weight loss and enteropathy. Firstly, we compared specific pathogen-free (SPF) OVA23-3 × BALB/cA mice with germ-free (GF) OVA23-3 × BALB/cA mice when fed an EW diet. Symptoms shown in SPF mice were attenuated in GF mice, suggesting that gut microbiota may contribute to exacerbating symptoms. Additionally, we orally administered broad-spectrum antibiotics (Abx) to OVA23-3×BALB/cA mice and analyzed the gut microbiota. Compared with a no-Abx administration group, we found that Abx administration significantly altered the alpha and beta diversity of the gut microbiota in EW-fed mice. The presence of Alloprevotella, Bacteroides, and Muribaculaceae was reduced to approximately 10%. Both weight loss and enteropathy in EW-fed mice were ameliorated after Abx administration. Furthermore, administration of Abx to the EW-fed group improved the Th1/Th2 balance in MLN cells and decreased the mRNA expression of IL-33 and the aryl hydrocarbon receptor in the jejunum. These results suggest that some members of the gut microbiota disturb Th1/Th2 responses in the MLN, by affecting the small intestinal epithelium, thereby exacerbating Th2-biased responses and inducing food-allergic enteropathy.
SN - 2186-3342
ER -