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Background <p>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.</p> Methods <p>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 <i>Caldifermentibacillus hisashii</i> 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 <i>C. hisashii</i> N11 (AP028807.1).</p> Results <p>Oral administration of <i>C. hisashii</i> 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 <i>C. hisashii</i> confirmed biosynthetic gene clusters for butyrate and AIB-containing lantibiotics, supporting the structural importance of these metabolites in diarrhoeal remission.</p> Conclusion <p>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 <i>C. hisashii</i> 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.</p> <p><MediaObject ID="MOESM3"> <VideoObject FileRef="MediaObjects/40168_2026_2476_MOESM3_ESM.mp4" VideoID="-brUQHV94FF3kj-gXshmQt"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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Gut-protective metabolic phenotype for diarrhoeal remission caused by an environmental probiotic thermophile

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • 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,
  • Hisashi Miyamoto,
  • Jun Kikuchi,
  • Masahira Hattori,
  • Takumi Nishiuchi,
  • Naoki Yamamoto,
  • Hiroshi Ohno

摘要

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.

Video Abstract