The interplay between microbes and the immune response in inflammatory bowel disease

Abstract

The aetiology and pathogenesis of inflammatory bowel disease (IBD) remains unclear but involves a complex interplay between genetic risk, environmental exposures, the immune system and the gut microbiota. Nearly two decades ago, the first susceptibility gene for Crohn's disease, NOD2, was identified within the IBD 1 locus. Since then, over 230 genetic risk loci have been associated with IBD and yet NOD2 remains the strongest association to date. As an intracellular innate immune sensor of bacteria, investigations into host-microbe interactions, involving both innate and adaptive immune responses, have become of particular interest in understanding the pathogenesis of IBD. Advancements in sequencing technology have lead to the groundbreaking characterization of the gut microbiota and its role in health and disease. While an altered microbiome has been described for IBD, whether it is a cause or an effect of the intestinal inflammation has yet to be determined. Moreover, the bidirectional relationship between the gut microbiota and the mucosal immune system adds to the multifaceted complexity of intestinal homeostasis. A better understanding of how host genetics, including NOD2, influence immune-microbe interactions and alter susceptibility to IBD is necessary in order to develop therapeutic and preventative treatments.

An Oral Rinse Active Matrix Metalloproteinase-8 Point-of-Care Immunotest May Be Less Accurate in Patients with Crohn’s Disease

“…Both CD and periodontitis have been linked to a disrupted immunological response to the local microbiota. The innate immune Biomolecules 2020, 10, 395 2 of 11 system, particularly neutrophils and their inadequate function, plays a major role in the pathogenesis of these diseases [8][9][10]. Of tissue-degrading matrix metalloproteinases (MMPs), MMP-8 is the key inflammatory mediator in their inter-relationship; elevated MMP-8 levels have been detected in CD patients both in the intestine and in the oral cavity [11,12].…”

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

“…These diseases are characterized by abdominal pain, diarrhea, rectal bleeding and bowel obstruction or fistulae [1]. Although IBD etiology is not yet fully understood, gut inflammation results from unregulated immune reactions in genetically susceptible individuals [2][3][4]. IBD response is driven by cytokines and leukocyte infiltrate in the gut [5][6][7], with histological features of crypt cell hyperplasia, interstitial edema and mucosa ulcerations [8].…”

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

“…An inauspicious alteration of the constitutional composition and variety of the gastrointestinal microbiota (dysbiosis) is observed and reported in IBD patients which affects the host immune system functionality and barrier integrity, resulting in chronic inflammation and aberrant immune responses [76]. Studies into host-microbe interactions, involving both innate and acquired/adaptive immune responses, have shown to be of particular interest in understanding the possible etiopathogenesis of IBD [76,77]. Evolutions in sequencing advance technology have triumphed to the groundbreaking findings and characterization of the gut microbiota and its role in health and disease.…”