Attributes of intestinal microbiota composition and their correlation with clinical primary nonresponse to anti-TNF-α agents in inflammatory bowel disease patients

  • Hanan Alatawi Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Biological Sciences, College of Science, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0000-0003-3476-5821
  • Mahmoud Mosli Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah , Saudi Arabia; Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia https://orcid.org/0000-0002-6975-1297
  • Omar I. Saadah Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia ; Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia https://orcid.org/0000-0002-3744-9907
  • Vito Annese Fakeeh University Hospital, Dubai, United Arab Emirates
  • Rashad Al-Hindi Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia https://orcid.org/0000-0002-4674-617X
  • Marfat Alatawy Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Biological Sciences, College of Science, University of Tabuk, Tabuk, Saudi Arabia.
  • Hadba Al-Amrah Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia https://orcid.org/0000-0002-3783-1890
  • Dikhnah Alshehri Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Biological Sciences, College of Science, University of Tabuk, Tabuk, Saudi Arabia. https://orcid.org/0000-0003-3261-8860
  • Ahmad Bahieldin Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetics, Ain Shams University, Cairo, Egypt https://orcid.org/0000-0002-6496-7881
  • Sherif Edris Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetics, Ain Shams University, Cairo, Egypt Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia https://orcid.org/0000-0002-2810-3736
Keywords: Inflammatory bowel disease, non-responders, microbiota

Abstract

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

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Published
2021-11-10
How to Cite
1.
Alatawi H, Mosli M, Saadah OI, Annese V, Al-Hindi R, Alatawy M, Al-Amrah H, Alshehri D, Bahieldin A, Edris S. Attributes of intestinal microbiota composition and their correlation with clinical primary nonresponse to anti-TNF-α agents in inflammatory bowel disease patients. Bosn J of Basic Med Sci [Internet]. 2021Nov.10 [cited 2021Dec.6];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/6436
Section
Microbiology