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IDDF2024-ABS-0442 A predictive machine learning model based on gut microbial signatures for clinical remission in inflammatory bowel disease treated with biologics: a comprehensive multi-cohort analysis
  1. Yun Zhong1,
  2. Haifeng Lian2,
  3. Zicheng Huang3,
  4. Qingyang Zheng1,
  5. Xuneng Zhang1,
  6. Bing Lan1,
  7. Zichuan He1,
  8. Jieru Zhuang1,
  9. Hui Wang1,
  10. Huaiming Wang1,
  11. Keli Yang1
  1. 1Department of General Surgery (Colorectal surgery), Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Key Laboratory of Human Microbiome and Chronic Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, China
  2. 2Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, China
  3. 3Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education; Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, China

Abstract

Background The onset and progression of inflammatory bowel disease (IBD) are closely associated with gut microbiota. Emerging evidence suggests a potential link between gut microbiota and the effectiveness of biologics in IBD. However, the specific gut microbial features that correlate with the effectiveness of biologics remain poorly defined. This study aims to identify specific gut microbial signatures for clinical remission (CR) in IBD patients treated with biologics and to develop a predictive machine-learning model based on these signatures.

Methods This meta-analysis included 2331 stool samples of 16S rRNA gene sequencing data from two independent studies (231 patients). All the participants were treated with biologics: 23 with infliximab, 22 adalimumab and 186 ustekinumab. Alterations in diversity and taxonomic compositions of gut microbiota were compared between patients with CR and those without (non-CR). A machine learning model was developed to predict CR based on gut microbial signatures.

Results Principal coordinate analysis showed significant differences in beta diversity between CR and non-CR patients across cohorts (P < 0.05), while no significant differences in alpha diversity were found (P > 0.05). Forty-one differential genera were identified between CR and non-CR patients. Notably, genera Parabacteroides B 862066, Lachnoclostridium B, Faecalibacterium, Faecousia, Onthenecus, SFMI01, Butyribacter, and Merdibacter were significantly decreased (P < 0.05) in the non-CR group, while UMGS1375 and Anaeroglobus were significantly increased. The prediction model, trained by the top 10 differential genera, effectively discriminates between patients achieving CR and non-CR with an area under the receiver operating characteristic curve of 0.80.

Conclusions This study is the first to demonstrate that IBD treatment outcomes are associated with distinct gut microbiota profiles across multiple cohorts. Significant changes in gut microbiota are associated with CR in patients treated with biologics. A machine learning model based on gut microbial signatures effectively predicted CR. Further studies are needed to explore the potential benefits of modulating the gut microbiome to improve the efficacy of biological treatments for IBD.

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