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

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          Abstract

          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 references45

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          Revised Estimates for the Number of Human and Bacteria Cells in the Body

          Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.
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            Proteobacteria: microbial signature of dysbiosis in gut microbiota.

            Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease.
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              Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans.

              According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.
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                Author and article information

                Journal
                1886
                European Journal of Microbiology and Immunology
                EuJMI
                Akadémiai Kiadó
                2062-8633
                September 2018
                : 8
                : 3
                : 63-69
                Affiliations
                [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@ 123456mmgc.eu

                Article
                10.1556/1886.2018.00017
                7506bc83-5b81-4a12-b7fb-87ba10bdeb43
                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), 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.

                History
                : 3 July 2018
                : 16 July 2018
                Page count
                Pages: 7
                Categories
                Review Paper

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                oral intake,endotoxaemia, E. coli ,safety,LPS,probiotic

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