Abstract

Intestinal tuberculosis (ITB) and Crohn’s disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.

Highlights

  • Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis, remains a public health problem and is one of the top 10 causes of death worldwide

  • There was no significant difference of age, gender, and body mass index (BMI) among patients with Crohn’s disease (CD), Intestinal tuberculosis (ITB), and healthy controls (HC)

  • In order to get a comprehensive profile of the gut microbiota, mucosal samples were collected from three intestinal segments of each subject, including ileum, ascending colon, and descending colon, and 16S rRNA gene sequencing was performed

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Summary

Introduction

Tuberculosis (TB), caused by the bacillus Mycobacterium tuberculosis, remains a public health problem and is one of the top 10 causes of death worldwide. About a quarter of the global population is infected with M. tuberculosis, and China is one of the 22 countries identified as having a high TB burden (World Health Organization, 2020). TB may involve any part of the body, including the lung, the primarily affected organ, and the gastrointestinal tract. Intestinal TB (ITB) is a chronic intestinal disease with non-specific clinical manifestation and endoscopic features, which were similar to Crohn’s disease (CD; He Y. et al, 2019). The therapeutic strategies between ITB and CD are completely different. ITB patients were treated with antituberculosis medication, while CD patients were administered immunosuppressive agents.

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