Microbial network disturbances in relapsing refractory Crohn’s disease

Abstract

Inflammatory bowel diseases (IBD) can be broadly divided into Crohn's disease (CD) and ulcerative colitis (UC) from their clinical phenotypes. Over 150 host susceptibility genes have been described, although most overlap between CD, UC and their subtypes, and they do not adequately account for the overall incidence or the highly variable severity of disease. Replicating key findings between two long-term IBD cohorts we have defined distinct networks of taxa associations within intestinal biopsies of CD and UC patients. Disturbances in an association network containing taxa of the Lachnospiraceae and Ruminococcaceae families, typically producing short chain fatty acids, characterize frequently relapsing disease and poor responses to treatment with anti-TNF-α therapeutic antibodies. Alterations of taxa within this network also characterize risk of later disease recurrence of patients in remission after the active inflamed segment of CD has been surgically removed.

Regulation of mononuclear phagocyte function by the microbiota at mucosal sites

“…These hyporesponsive properties of intestinal macrophages are thought to be a key contributor to the prevention of overactive harmful immune responses against the microbiota that occur during IBD. Indeed, in humans, intestinal macrophages from the inflamed mucosa in IBD produce excess pro‐inflammatory cytokines in response to LPS and low butyrate levels are found in the intestine in human IBD . Butyrate is recognized by cell surface expression of G‐protein‐coupled receptors including GPR109a, which is essential for the anti‐inflammatory effects of butyrate on intestinal macrophages .…”

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…Furthermore, in Crohn's disease, the abundance of Eggerthella , Clostridiales , and Oscillospira (Firmicutes) increased in patients with quiescent disease, whereas Enterobacteriaceae (among which Klebsiella ) were associated with a more severe clinical course. No significant differences were highlighted comparing patients with ulcerative colitis responding to anti‐TNF therapy with patients failing to respond to treatment …”

“…58 Recently, Yilmaz and collaborators published a similar paper focused on the role of microbiota composition in two independent long-term IBD cohorts (cohort 1 = 346 patients; cohort 2 = 156 patients). 59 Interestingly, patients with Crohn's disease responsive to infliximab or adalimumab therapy showed an increase of Actinobacteria, including Bifidobacterium, Eggerthella, and Collinsella, and Firmicutes, such as Lachnospira and Roseburia, and reduced Phascolarctobacterium (Firmicutes). Most of these taxa, in particular Lachnospiraceae and Roseburia, produce SCFA metabolites, which have important anti-inflammatory properties.…”

“…No significant differences were highlighted comparing patients with ulcerative colitis responding to anti-TNF therapy with patients failing to respond to treatment. 59 To determine whether the gut microbiome can predict responses to the anti-integrin monoclonal antibody vedolizumab in IBD, Ananthakrishnan et al 60 conducted a prospective study enrolling 85 patients at the beginning of the therapy (baseline microbiota), and at weeks 14, 30, and 54 after therapy initiation. Only patients with Crohn's disease achieving remission at week 14 showed a significantly more diversified microbiome composition and Roseburia inulinivorans and Burkholderiales species were more abundant.…”

Systematic interrogation of the distinct metabolic potential in gut microbiomes of inflammatory bowel disease patients with dysbiosis

“…AGORA enables the creation of personalized microbiome models from metagenomics data (Baldini et al, 2018) and has valuable applications in studying microbe-microbe and host-microbe interactions . AGORA has been successfully applied to investigating host-microbe interactions in colorectal cancer (Hale et al, 2018), predicting microbial cross-feeding at suboptimal growth (Henson and Phalak, 2018), modelling the lung microbiome in Cystic Fibrosis patients (Henson et al, 2019), predicting dietary supplements that promote short-chain fatty acid production in Crohn's Disease patients (Bauer and Thiele, 2018), and analyzing microbial network patterns in relapsing Crohn's Disease (Yilmaz et al, 2019).…”