The Characteristics and Function of Bacterial Lipopolysaccharides and Their Endotoxic Potential in Humans

Abstract

Cross-talk between enteral microbiota and human host is essential for the development and maintenance of the human gastrointestinal and systemic immune systems. The presence of lipopolysaccharides (LPS) lysed from the cell membrane of Gram-negative bacteria in the gut lumen is thought to promote the development of a balanced gut immune response whilst the entry of the same LPS into systemic circulation may lead to a deleterious pro-inflammatory systemic immune response. Recent data suggest that chronically low levels of circulating LPS may be associated with the development of metabolic diseases such as insulin resistance, type 2 diabetes, atherosclerosis and cardiovascular disease. This review focuses on the cross-talk between enteral commensal bacteria and the human immune system via LPS. We explain the structural characterisation of the LPS molecule and its function in the bacteria. We then examine how LPS is recognised by various elements of the human immune system and the signalling pathways that are activated by the structure of the LPS molecule and the effect of various concentrations. Further, we discuss the sequelae of this signalling in the gut-associated and systemic immune systems i.e. the neutralisation of LPS and the development of tolerance to LPS.

Analysis of Bacterial Lipooligosaccharides by MALDI-TOF MS with Traveling Wave Ion Mobility

“…Recognition of Gram-negative bacteria by the innate immune system involves binding of LOS or LPS with Toll-like receptor 4 (TLR4) on human cells, which induces inflammatory cytokines and engages host defense mechanisms [5]. Variation in structural features of the lipid A and oligosaccharide components of LOS can be correlated with differences in bioactivity [5].…”

“…Variation in structural features of the lipid A and oligosaccharide components of LOS can be correlated with differences in bioactivity [5]. A key determinant of toxicity and pathophysiology of infections with Neisseria spp.…”

Cocaine- and amphetamine-regulated transcript (CART) peptide in the nerve fibres of the porcine gallbladder wall under physiological conditions and after Salmonella Enteritidis lipopolysaccharides administration

“…Probably these mechanisms take place even in the case of low doses of LPS using during the present study. On the other hand, changes observed in this investigation can be connected with other actions of LPS, such as the blockade of synaptic transmissions, neurodegenerative activity and/or the influence on sensory stimuli conduction [6,11,31]. Direct reasons of observed changes are also not clear.…”

“…First of all, the fluctuation in CART-like immunoreactivity may be connected with relatively well-known pro-inflammatory effects of LPS [11]. This LPS activity has been also described within the enteric nervous system, where bacterial endotoxins caused the significant increase in the synthesis of the major pro-inflammatory cytokine -tumour necrosis factor-alpha [6].…”

“…Previous studies described, among others, LPS-induced cholecystitis and fluctuations in mucin secretion by gallbladder epithelial cells [5,20], but the changes in the innervation of this organ after LPS administration has not been investigated at all. Moreover, the majority of previous studies concerned the high doses of LPS [11,19,20], while this study was performed on "low single dose", which can simulate the asymptomatic carrier state of Salmonella spp.…”