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

Hanan Alatawi,Mahmoud Mosli,Marfat Alatawy,Dikhnah Alshehri,Sherif Edris,Ahmad Bahieldin,Rashad Al-Hindi,Hadba Al-Amrah,Omar I Saadah,Vito Annese

doi:10.17305/bjbms.2021.6436

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 key role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influence unresponsiveness to anti-TNF-α treatments in primary non-responder 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 or Crohn’s disease, 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 non-responder 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 was identified as predictors of clinical non-response 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 non-response 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 non-responders to anti-TNF-α therapy.

Highlights

Ulcerative colitis (UC) and Crohn’s disease (CD) are the primary subtypes of inflammatory bowel disease (IBD), found in individuals with genetic susceptibility subject to particular environmental conditions [1]
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 intestinal microbiota performs a vital role in the degradation of indigestible carbohydrates to produce short-chain fatty acids (SCFAs), and is important for vitamins synthesis, amino acids synthesis, and regulation of fat metabolism

Summary

Introduction

Ulcerative colitis (UC) and Crohn’s disease (CD) are the primary subtypes of inflammatory bowel disease (IBD), found in individuals with genetic susceptibility subject to particular environmental conditions [1]. According to various molecular studies in a number of different cultures with various genetic profiles, more than 1000 species of microbiota colonize the gastrointestinal ecosystem, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria [2, 6]. The intestinal microbiota performs a vital role in the degradation of indigestible carbohydrates to produce short-chain fatty acids (SCFAs), and is important for vitamins synthesis (vitamin K, vitamin B12, and folic acid), amino acids synthesis, and regulation of fat metabolism. All these processes are necessary for the preservation of intestinal barrier functions [7]. Microbiota present in colonic epithelial cells consume butyrate to produce energy, while acetate and propionate remain in the intestinal cell [9]

Objectives

Methods

Results

Discussion

Conclusion