Baseline Gut Microbiome-Dependent Responses to Probiotic Treatments for IBD in Mice

Zeng Zhang , Zhihan Yang , Shuaiming Jiang , Yukai Sun , Yuesong Jiang , Shi Huang , Jiachao Zhang

Engineering ›› : 202502025

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Engineering ›› :202502025 DOI: 10.1016/j.eng.2025.02.025
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Baseline Gut Microbiome-Dependent Responses to Probiotic Treatments for IBD in Mice
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Abstract

Inflammatory bowel disease (IBD) is a significant global health issue, with probiotic interventions offering a potential avenue for personalized treatment. However, the IBD-associated gut microbiome can be highly individualized, which contributes to the observed poor effectiveness of probiotics. This study evaluated the effects of the probiotic Lactobacillus reuteri HNU872 in genetically identical mice with distinct baseline microbiomes, using an IBD model. Co-abundance network and clustering analyses were used to identify distinct health- and disease-associated microbial guilds. We found that a higher abundance of disease-associated guilds led to the compromise of the microbial network stability, IBD exacerbation, and an increase in probiotic receptivity. Multi-omics analysis demonstrated that the composition of baseline guilds affected probiotics’ ability to modulate indole-3-carboxylic acid and indole-3-propionic acid, and influence inflammation, immune gene expression, and treatment efficacy. These findings were validated using published microbiome data on IBD and probiotic treatments. We also verified these findings beyond strain-specific effects by repeating the experiment using Lactobacillus plantarum HNU082, a probiotic previously reported to exhibit anti-inflammatory properties in IBD mice. This study underscores the importance of baseline microbiome composition in determining IBD severity and probiotic effectiveness, highlighting the need for personalized probiotic therapies tailored to individual microbiomes.

Keywords

Inflammatory bowel disease / Guild / Baseline gut microbiome / Personalized probiotic therapies / Lactobacillus reuteri HNU872

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Zeng Zhang, Zhihan Yang, Shuaiming Jiang, Yukai Sun, Yuesong Jiang, Shi Huang, Jiachao Zhang. Baseline Gut Microbiome-Dependent Responses to Probiotic Treatments for IBD in Mice. Engineering 202502025 DOI:10.1016/j.eng.2025.02.025

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