In humans, intestinal flora (also called the microbiome) is made of numerous bacterial communities which play a key role in the immunology of the gastrointestinal tract. Unfortunately, several pathophysiological factors can disturb the normal flora and lead to ‘dysbiosis’, defined as a disequilibrium among these communities. The gastrointestinal mucosal immune system detects and clears most food-borne pathogens, and keeps potential opportunists under control without excess harm to beneficial bacteria and host tissues. A central component of the mucosal immune system is the sophisticated system of receptors that recognize microbial products. Primary classes of such receptors include the Toll-like (TLR) receptors that recognize a variety of bacterial products including lipopolysaccharide (LPS), flagellin, peptidoglycan, and bacterial DNA. The primary consequence of TLRs is to induce host-defense gene expression that can protect against numerous microbes. Today, it is well recognized that the main TLR pathway is mediated by the TLR4 receptor, which is triggered by LPS, its main ligand.
LPS is a structural component of intestinal gram-negative bacteria. Triggering TLR4 receptors lead to a cascade of immunological events involving numerous cytokines and chemokines, including TNF-alpha and interleukins. These signaling pathways cause an increased gut permeability and mucosal inflammation. So far, most of the clinical experience on LPS neutralization has come from the area of sepsis. The essential role of LPS in sepsis has led to the clinical use of LPS binding agents like polymyxin B, which has become the reference product in this application.
Ulcerative colitis (UC) and Crohn’s disease (CD) are both inflammatory bowel diseases (IBD) and are characterized by an exaggerated immune response at the gut associated lymphoreticular tissue level. Such an abnormal and dysregulated immune response may be directed against luminal and/or enteric bacterial antigens, as also supported by IBD murine models caused by microorganisms. Bacterial endotoxins and LPS have been detected in the plasma of IBD patients and an abnormal microflora and/or an increased permeability of the intestinal mucosa have been invoked as cofactors responsible for endotoxemia. In IBD, pro-inflammatory cytokines and chemokines are present in elevated amounts in mucosal tissue and in peripheral blood.

Moreover, LPS derived from intestinal gram negative bacteria appear to play a key role in the inflammation cascade and its persistence in celiac disease. Mucosal TLR4 receptors are triggered by LPS, inducing immunological signalling pathways leading to increased gut permeability and epithelial cells tight junctions abnormalities. While LPS may not be the leading causal factor in celiac disease, it does participate to the mucosal damage process and associated malabsorption problems. Several studies point towards alteration in gut microbiota composition and function in celiac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce celiac- disease-associated immunopathology. Animal models have provided proof-of-concept studies demonstrating that host responses to gluten can be modified by the composition of the gut microbiome.
Finally, it is well established that acute gastrointestinal infections initiate the onset of symptoms in at least a subgroup of patients with Irritable Bowel Syndrome (IBS), in particular with its diarrhea predominant form (IBS-D). Some IBS patients display persistent signs of low-grade mucosal inflammation with activated T lymphocytes, mast cells, and enhanced expression of pro-inflammatory cytokines. Because major risk factors for the development of post-inflammatory abdominal symptoms include the intensity and duration of an acute inflammation, it might be speculated that immune activation predicts the symptom pattern and severity. Innate immune responses to LPS and flagellin are likely important in microbial–host interactions and intestinal homeostasis. It is currently hypothesized that bacterial translocation and activation of mucosal immunity against common microbial antigens might be involved in the development of IBS. Moreover, post-infectious IBS, which bears close resemblance to IBS-D, is a surprisingly common result of acute gastroenteritis (primarily of bacterial aetiology) with a 30 % reported incidence. The suggested pathophysiologic mechanisms include increased intestinal permeability, altered motility, and persistent intestinal inflammation.