Metabolic endotoxemia

Cani, P. D., BibUoni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., et al. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 57(6), 1470-1481. 

Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 56 1761—1772. 

The first question has been well addressed by Cani et al. (2007) who demonstrated that lipopolysaccharide (LPS) from Gram-negative bacteria can translocate from the gut lumen to the blood stream causing "metabolic endotoxemia" leading to a low-grade systemic inflammation and obesity, a state that may also be triggered in response to HFD feeding (discussed in the section Interactions between Gut Microbes and Obesity "The Inflammation Theory"). 

Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 56(7) 1761—1772. Neyrinck AM, Possemiers S, Verstraete W, De Backer F, Cani PD, Delzenne NM. Dietary modulation of clostridial cluster XlVa gut bacteria (Roseburia spp.) by chitin-glucan fiber improves host metabolic alterations induced by high-fat diet in mice. / Nutr Biochem. 2012 23... 

Gut microbiota composition may also modulate systemic inflammation. LPS, a constituent of Gram negative bacteria triggers the secretion of proinflammatory molecules. Elevated LPS levels in blood circulation, mainly through a high-fat diet, contribute to metabolic endotoxemia which modulate glucose and insulin metabolism... 

Neyrinck AM, Van Hee VF, Piront N, et al. Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogerric gut peptides and reduce metabolic endotoxemia in diet-induced obese mice. Nutr Diabetes. 2012 2 e28. 

Chylomicron and high density lipoprotein metabolism Endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes 178... 

Raised concentrations of lithocholate, portal bacteremia, and/or endotoxemia have all been suggested as contributing to hepatic triaditis in patients with inflammatory bowel disease receiving parenteral nutrition. Toxic amino acids or their metabolic products, excessive calorie administration and a disturbed carbohydrate/protein... 

In the non-exercising horse, increased blood lactate concentrations are sufficient evidence of a metabolic disturbance to initiate fluid therapy. They are an indication of poor tissue perfusion or increased circulating epinephrine (adrenaline) concentrations (James et al 1999). Hypovolemia and endotoxemia are common causes of increased lactate concentrations in the horse. Endotoxemia increases tissue lactate production both through circulatory changes, which reduce blood flow to the tissues and inappropriate anaerobic metabolism (Fink 1997). Whereas lactate is a good indicator of the need to start fluid therapy, continued high lactate concentrations should be assessed in the context of cardiovascular parameters, such as pulse rate, urine output and blood pressure, because decreases in plasma lactate concentration... 

As discussed, increased blood or plasma lactate concentrations are usually caused by poor tissue perfusion in gastrointestinal diseases but may also result from acute renal failure, hepatic failure and anaerobic metabolism during endotoxemia. The clinical signs related to the disease causing the lactic acidosis are likely to overshadow the direct effects of the lactemia, such as decreased myocardial contractility (Yatani et al 1981). 

Armstrong, J., Tempel, G.E., Cook, J.A., Wise, W.C. and Halushka, P.V. (1986). The effects of alpha adrenergic blockade on arachidonic acid metabolism and shock sequelae in endotoxemia. Circ. Shock, 20, 151-159... 

Ivanyi Z, Hauser B, Pittner A et al. Systemic and hepatosplanchnic hemodynamic and metabolic effects of the PARP inhibitor PJ34 during hyperdynamic porcine endotoxemia. Shock 2003 19 415-21. 

The mechanism of induction of low-grade chronic inflammation that accompanies HF-diet-induced obesity was demonstrated to be dependent on TLR-4. Interestingly, in the absence of TLR-4/CD14 receptor for LPS, no low-grade chronic inflammation and insulin resistance were induced by HF feeding in mice. Recently also TLR-2 and TLR-5 were shown to be involved in the innate immune system activation that is responsible for the inflammation induced after HF diet. These results confirm gut microbiota implication in the onset of metabolic disorders associated with obesity. Moreover, in animal studies at least, this high-fat-induced metabohc endotoxemia and subsequent metabolic disease may be reversed using prebiotic dietary fibers and certain bacterial supplements... 

Severe multisystem trauma, endotoxemia, or situations in which there is a raised metabolic demand for thiamin, such as pregnancy, thyrotoxicosis, and intercurrent illness or impaired absorption (e.g., alcohol abuse or gastrointestinal disease or resection), can produce subclinical evidence of thiamin deficiency or more severe life-threatening aspects of beriberi, such as renal and/or cardiovascular failure. The elderly may be particularly at risk of subclinical thiamin deficiency. One Belgian study on patients with a mean age of 83 years reported that 40% had a raised TDP effect (>15%), in whom there was a high proportion of Alzheimer s disease, depression, cardiac failure, and falls. The diuretic furosemide was also more frequently taken by the thiamin-deficient patients. 

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