喫煙による潰瘍性大腸炎の症状緩和の成因を解明~喫煙が腸内環境に与える影響を明らかに~

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2025-08-26 理化学研究所,群馬大学,順天堂大学,東京慈恵会医科大学,日本医療研究開発機構

理化学研究所らの共同研究グループは、喫煙が腸内環境を介して潰瘍性大腸炎(UC)の症状を緩和する仕組みを解明しました。UC患者の解析では、喫煙者の便中で芳香族化合物(ヒドロキノン等)が増加し、大腸粘膜で口腔内細菌(Streptococcus, Haemophilus)が増えることが判明。これらの代謝物は一部細菌の増殖を促進し、腸内細菌叢を変化させました。さらに、Streptococcusを投与したUCモデルマウスではTh1細胞が増加し、Th2応答が抑制され炎症が緩和。この結果、喫煙が腸内細菌と免疫応答を変化させUCを軽減する可能性が示されました。本知見は禁煙後の症状悪化理解や、新たな腸内環境を標的とした治療法開発につながると期待されます。成果は『Gut』に掲載されました。

喫煙による潰瘍性大腸炎の症状緩和の成因を解明~喫煙が腸内環境に与える影響を明らかに~
喫煙が腸内環境に与える影響

<関連情報>

喫煙は、代謝プロファイルと粘膜微生物叢を調節することで、炎症性腸疾患患者の腸免疫系に影響を与える Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota

Eiji Miyauchi,,Takashi Taida,,Kan Uchiyama,Yumiko Nakanishi,Tamotsu Kato,Shigeo Koido,Nobuo Sasaki,Toshifumi Ohkusa,Nobuhiro Sato,Hiroshi Ohno
Gut  Published: August 25, 2025
DOI:10.1136/gutjnl-2025-334922

Abstract

Background The aetiology and pathogenesis of IBD are intricate, involving genetic and environmental factors. Notably, cigarette smoking has contrasting effects, being detrimental to Crohn’s disease (CD) and beneficial to UC. However, the mechanisms underlying these opposite effects remain unclear.

Objective This study aimed to elucidate the precise mechanisms by which smoking influences IBD pathogenesis, by focusing on the roles of microbiota and metabolomics.

Design We analysed the microbiota composition of saliva, faeces and the colonic mucosa, and the faecal metabolite profile of patients with IBD and healthy participants. The effects of smoking-associated bacteria on the gut immune system and colitis were evaluated using gnotobiotic mice and murine models of UC and CD.

Results People with UC who smoke showed increased concentrations of short-chain fatty acids and aromatic compounds in the faeces compared with the people who quit smoking. The analysis of the mucosal microbiota revealed that smoking is associated with the increased oral bacteria in the colonic mucosa. Monocolonisation of germ-free mice with Streptococcus mitis, one of the oral bacteria ectopically increased in the colonic mucosa, induced interferon (IFN)-γ-producing T cells in the colon. S. mitis also attenuated inflammation in a murine model of UC but exacerbated it in a CD model.

Conclusion We demonstrated that smoking affects the gut immune system by modulating mucosal microbiota. Our findings provide insights into how smoking can have beneficial or detrimental effects on UC or CD, respectively, and may shed light on the reasons why individuals with UC who quit smoking experience disease exacerbation.

医療・健康
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