家畜における一過性腸内かく乱を改善する好熱菌 -離乳期の下痢寛解のための分子機序の推察-

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2026-08-21 理化学研究所,九州大学,千葉大学,金沢大学,広島大学,北里大学,慶應義塾大学先端生命科学研究所,国立健康危機管理研究機構

理化学研究所、九州大学、千葉大学などの共同研究グループは、好熱菌 Caldifermentibacillus hisashii(C. hisashii)を含む高温発酵飼料が、黒毛和種子牛の一過性の下痢を寛解させる現象と、その作用機序の一端を明らかにした。フィールドモデル試験で投与前後の糞便を調べ、腸内細菌叢・代謝物・投与菌のゲノム・プロテオームを統合したマルチオミクス解析を実施。その結果、下痢寛解に伴って酪酸や2-アミノイソ酪酸(AIB)などの代謝物が変化し、C. hisashiiには酪酸生合成経路とAIBを含むランチビオティックの生合成遺伝子クラスターが存在することを確認した。これらが腸内代謝環境を調節し、腸管保護や病原性微生物の抑制を通じて下痢改善に寄与する可能性が示された。抗菌薬への依存を減らし、薬剤耐性菌対策や持続可能な畜産、One Healthへの貢献が期待される。

家畜における一過性腸内かく乱を改善する好熱菌 -離乳期の下痢寛解のための分子機序の推察-
本研究の概要

<関連情報>

環境プロバイオティクス好熱菌による下痢寛解のための腸管保護代謝表現型 Gut-protective metabolic phenotype for diarrhoeal remission caused by an environmental probiotic thermophile

Hirokuni Miyamoto,Hideyuki Takahashi,Wataru Suda,Haruki Yamano,Yudai Inabu,Hiroaki Kodama,Yumiko Nakanishi,Shigeharu Moriya,Takashi Satoh,Tamotsu Kato,Chie Shindo,Naoko Tsuji,Makiko Matsuura,Chitose Ishii,Teruno Nakaguma,Tetsuji Etoh,Yuji Shiotsuka,Motoaki Udagawa,Atsushi Kurotani,Kenta Suzuki,Hiroshi Masuya,Satoshi Wada,Shinji Fukuda,Yukihiro Tashiro,… Hiroshi Ohno
Microbiome  Published:05 August 2026
DOI:https://doi.org/10.1186/s40168-026-02476-9

Abstract

Background
Controlling diarrhoea in humans and livestock is a global challenge with diverse aetiologies. However, the dynamics of the microbiome for diarrhoeal remission are not sufficiently understood, and effective intervention strategies based on environmental microorganisms have not been fully explored.

Methods
We investigated the metabolic structure associated with diarrhoeal remission using a combination of statistical, genomic, and proteomic approaches in a cattle model. Oral administration of the compost-derived thermophile Caldifermentibacillus hisashii significantly ameliorated persistent diarrhoea. Faecal bacterial populations and metabolites were characterised by a multi-step statistical pipeline comprising difference-in-differences (DID) analysis, Cliff’s delta effect size estimation with permutation-based validation. The functional importance of the selected feature components was validated through genomic and proteomic analysis of C. hisashii N11 (AP028807.1).

Results
Oral administration of C. hisashii significantly ameliorated persistent diarrhoea in calves. Although no significant differences in faecal bacterial community composition were observed, integrated analysis of faecal metabolites identified butyrate and 2-aminoisobutyrate (AIB) as the most discriminative features associated with diarrhoeal remission. Genomic and proteomic analyses of C. hisashii confirmed biosynthetic gene clusters for butyrate and AIB-containing lantibiotics, supporting the structural importance of these metabolites in diarrhoeal remission.

Conclusion
These findings suggest that diarrhoeal remission observed in this study involves characteristic shifts in faecal metabolite profiles rather than marked changes in overall gut microbial community composition, highlighting a protective role of C. hisashii as an environmental probiotic against diarrhoeal dysbiosis through modulation of gut microbial metabolic output. This offers a perspective that bridges environmental microbiology and gut health within a One Health framework.

生物化学工学
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