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

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.

Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis

“…Estevinho et al ( 35 ) observed a lower abundance of Escherichia coli and a higher abundance of SCFA-producing bacteria in anti-TNF therapy responders than in nonresponders. Likewise, a prior study ( 36 ) demonstrated that anti-TNF therapy nonresponders exhibited a reduction in biodiversity and SCFA-producing bacteria. Our study indicated a higher phylum-level abundance of Verrucomicrobiota in patients with remission than in the nonremission group.…”

Distinct alterations of fecal microbiota refer to the efficacy of adalimumab in Crohn’s disease

“…A comparison of fecal samples from the ADA-responsive and ADA-nonresponsive groups shows that the gut microbiota structure of the responsive group is clearly modified during the treatment period. In detail, protective bacterial genera such as Barnesiella , Anaerostipes , Tyzzerella , Lachnoclostridium , and Lachnospiraceae were found increased in the ADA-responsive samples , while pathogenic bacterial taxa such as Escherichia–Shigella genera were diminished contrarily ( Zhuang et al, 2020 ; Alatawi et al, 2021 ; Mo et al, 2021 ; Chen et al, 2022 ). Such modifications have been reported to reverse the disturbance of the microecosystem, produce more short-chain fatty acids, and correct immunity imbalance ( Cho et al, 2012 ; Meehan and Beiko, 2014 ), indicating that these bacteria may serve as potential microbiota biomarkers for predicting ADA treatment responses.…”

Sub-Chronic Difenoconazole Exposure Induced Gut Microbiota Dysbiosis in Mice

“…Dysgonomonas and Butyricicoccus were considered to be potential probiotic bacteria [34,35]. Roseburia and Ruminococcus could produce short chain fatty acids [36,37]. The short chain fatty acids were fermented by some gut microbiota and played an important role in gut health [38].…”