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      Lipopolysaccharides in food, food supplements, and probiotics: should we be worried?

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          The fever-inducing effect of lipopolysaccharides (LPS) is well known, and human blood is extremely responsive to this pyrogen. Recently, the safety of LPS-containing food supplements and probiotic drugs as immune-stimulants has been questioned, although these products are orally taken and do not reach the bloodstream undigested. The concerns are understandable, as endotoxaemia is a pathological condition, but the oral uptake of probiotic products containing LPS or Gram-negative bacteria does not pose a health risk, based on the available scientific evidence, as is reviewed here. The available methods developed to detect LPS and other pyrogens are mostly used for quality control of parentally applied therapeuticals. Their outcome varies considerably when applied to food supplements, as demonstrated in a simple comparative experiment. Products containing different Escherichia coli strains can result in vastly different results on their LPS content, depending on the method of testing. This is an inherent complication to pyrogen testing, which hampers the communication that the LPS content of food supplements is not a safety concern.

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          Most cited references 37

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          Metabolic endotoxemia with obesity: Is it real and is it relevant?

          Obesity is associated with metabolic derangements in multiple tissues, which contribute to the progression of insulin resistance and the metabolic syndrome. The underlying stimulus for these metabolic derangements in obesity are not fully elucidated, however recent evidence in rodents and humans suggests that systemic, low level elevations of gut derived endotoxin (lipopolysaccharide, LPS) may play an important role in obesity related, whole-body and tissue specific metabolic perturbations. LPS initiates a well-characterized signaling cascade that elicits many pro- and anti-inflammatory pathways when bound to its receptor, Toll-Like Receptor 4 (TLR4). Low-grade elevation in plasma LPS has been termed "metabolic endotoxemia" and this state is associated with a heightened pro-inflammatory and oxidant environment often observed in obesity. Given the role of inflammatory and oxidative stress in the etiology of obesity related cardio-metabolic disease risk, it has been suggested that metabolic endotoxemia may serve a key mediator of metabolic derangements observed in obesity. This review provides supporting evidence of mechanistic associations with cell and animal models, and provides complimentary evidence of the clinical relevance of metabolic endotoxemia in obesity as it relates to inflammation and metabolic derangements in humans. Discrepancies with endotoxin detection are considered, and an alternate method of reporting metabolic endotoxemia is recommended until a standardized measurement protocol is set forth.
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            A guiding map for inflammation

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              Bacterial sensing, cell signaling, and modulation of the immune response during sepsis.

              Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. The complexity of the infection/injury-induced immune response could be better appreciated with the application of genomics and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.

                Author and article information

                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                September 2018
                : 8
                : 3
                : 63-69
                [1 ] Molecular Microbiology and Genomics Consultancy , Tannenstrasse 7, 55576 Zotzenheim, Germany
                [2 ] SymbioPharm GmbH , Herborn, Germany
                Author notes

                Corresponding author: Trudy M. Wassenaar, Molecular Microbiology and Genomics Consultancy, Tannenstrasse 7, 55576 Zotzenheim, Germany; trudy@

                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.

                Page count
                Pages: 7
                Review Paper


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