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bacterial lipopolysaccharide membrane model

Lipopolysaccharide (LPS)


Lipopolysaccharide (LPS), a potent endotoxin present in the outer membrane of Gram-negative bacteria, causes chronic immune responses associated with inflammation. LPS are chemical molecules located in the outer membrane of Gram-negative bacteria.

Lipopolysaccharide (LPS) is a molecule found on the outer surface of certain types of bacteria. It is made up of a lipid (fat) and a polysaccharide (sugar) and serves as a protective barrier for the bacteria. LPS is also known as endotoxin because it can cause a toxic reaction when it enters the body.

In the human body, LPS is found mainly in the outer membranes of gram-negative bacteria, which are a type of bacteria with a thin outer membrane and are characterized by their ability to resist certain antibiotics. When gram-negative bacteria die or are disrupted, LPS can be released into the body and trigger an immune response. This immune response can cause inflammation, fever, and other symptoms.

LPS has also been shown to play a role in developing certain autoimmune and inflammatory disorders, such as sepsis and multiple sclerosis. However, the exact mechanisms by which LPS contributes to these conditions are not fully understood, and more research is needed to clarify its role.

Lipopolysaccharides and Inflammation

LPS promotes inflammation mainly by signaling through Toll-like receptor (TLR) 4 on macrophages, monocytes, and other cells of the innate immune system. [x  Emerging data supports the association of TLR4 and TLR4 polymorphisms with several diseases with an inflammatory etiology, including cancer, atherosclerosis, and autoimmune conditions.  

A number of studies also suggest a possible role of TLR4 in cardiovascular disease [x,x], inflammatory bowel disease [x], Alzheimer’s disease [x], rheumatoid arthritis [x], renal disease [x], obesity, and both type I and type II diabetes [x]. The increasing body of evidence suggesting a link between TLR4 and many diseases suggests that developing therapeutic compounds that target this receptor may generate some tremendously important advances in the coming years. 

ObesityRecently, it has been shown that obesity is associated with chronic and systemic low-grade inflammation which is due to an innate immune response to LPS. It is considered an endotoxin and found at low concentrations in the blood of healthy persons. But substantially high concentrations of LPS have been demonstrated in obese individuals, where the obesity is diet-induced and has a genetic predisposition.  

Studies found that plasma levels of LPS were elevated in obese individuals compared with controls (P < 0.001) and were reduced after bariatric surgery [x], suggesting that translocation of gut bacteria are a potential trigger for obesity and diabetes and that the antidiabetic effects of bariatric surgery may be owed to this mechanism.
Diabetes Type IIDiabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both [x] .

The prevalence and incidence of DM have increased recently, especially in Western countries [x]. Short and long-term complications due to uncontrolled glycemia lead to high human, social, and economic burdens [x]. Therefore, understanding the features involved in the pathophysiology of DM is of considerable value in treating DM and preventing its progression. 

The data indicate that DM favors LPS endotoxin translocation across the intestinal barrier, leading to its mild increase in concentration in the bloodstream [x].   The Lipid A component is responsible for much of LPS toxicity. Toll-like receptors (TLR) of the innate immune system recognize lipid A and then trigger immune and inflammatory responses in DM models [x].   

Systematic Reviews find that diabetic subjects present higher fasting and postprandial LPS concentrations compared to lean non-diabetic subjects and/or obese subjects. [x]  Evidence also suggests that LPS endotoxin is involved in the onset of Type 1 Diabetes Mellitus since LPS concentrations were also higher at the disease onset [x,x]
AutismIn recent years, there has been an emerging interest in the possible role of the gut microbiota as a co-factor in the development of autism spectrum disorders (ASDs), as many studies have highlighted the bidirectional communication between the gut and brain (the so-called “gut-brain axis”). Accumulating evidence has shown a link between alterations in the composition of the gut microbiota and both gastrointestinal and neurobehavioural symptoms in children with ASD.  

A maternal high-fat diet during pregnancy alters the microbiota in neonates and appears to be associated with ASD in humans [x]  A considerable number of subjects with ASD have significant gastrointestinal dysfunction, particularly altered bowel habits and chronic abdominal pain that accompany their neurological alterations [x].  Further, the gastrointestinal (GI) symptoms of individuals with ASD seem to correlate strongly with the severity of their ASD [x]

In recent years, several studies have shown significant changes in the composition of the gut microbiota in children with ASD [x,xand have suggested that GI symptoms in ASD may be a manifestation of the underlying inflammatory process [x]. In particular, dysbiosis is associated with a disruption of the mucosal barrier that leads to increased intestinal permeability of exogenous peptides of dietary origin or neurotoxic peptides of bacterial origin such as lipopolysaccharide [x]

The microbiota and its metabolites are crucial in maintaining epithelial barrier integrity; therefore, dysbiosis in ASD patients may alter gut permeability [x]. This condition, called “leaky gut” [x], may allow the passage of bacteria, toxins such as LPS, and metabolites that activate the immune response and induce an inflammatory state into the bloodstream [x]

Lipopolysaccharide (LPS) Summary

• Lipopolysaccharide (LPS) is a molecule found on the outer surface of certain types of bacteria, made up of lipids and polysaccharides.

• It can cause an immune response when it enters the body, leading to inflammation, fever, and other symptoms.

• LPS has also been linked to autoimmune and inflammatory disorders such as sepsis and multiple sclerosis.

• It promotes inflammation mainly by signaling through Toll-like receptor 4 on macrophages or monocytes in the innate immune system.

• Obesity is associated with chronic low-grade inflammation due to an innate immune response from LPS; bariatric surgery reduces plasma levels of LPS in obese individuals suggesting that translocation may be involved in obesity development.

• Diabetes Type II has been shown to favor endotoxin translocation across the intestinal barrier leading a mild increase in blood concentration; evidence suggests involvement at onset for Type I diabetes mellitus as well since concentrations were higher at disease onset than controls or non-diabetics

• Autism spectrum disorder patients have significant changes/alterations in gut microbiota composition, which leads to increased permeability allowing passage for toxins such as lipopolysaccharides into the bloodstream, activating immune responses and inducing an inflammatory state.

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