The gut microbiota - masters of host development and physiology.

1] Wallenberg Laboratory for Cardiovascular and Metabolic Research, Sahlgrenska University Hospital, Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden. [2] Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
Nature Reviews Microbiology (Impact Factor: 23.32). 02/2013; DOI: 10.1038/nrmicro2974
Source: PubMed

ABSTRACT Establishing and maintaining beneficial interactions between the host and its associated microbiota are key requirements for host health. Although the gut microbiota has previously been studied in the context of inflammatory diseases, it has recently become clear that this microbial community has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism. The underlying molecular mechanisms of host-microorganism interactions remain largely unknown, but recent studies have begun to identify the key signalling pathways of the cross-species homeostatic regulation between the gut microbiota and its host.

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    ABSTRACT: The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.
    PLoS ONE 01/2015; 10(3):e0120261. DOI:10.1371/journal.pone.0120261 · 3.53 Impact Factor
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    ABSTRACT: A healthy gut with normal intestinal microflora is completely disrupted by oral antibiotics. The byproducts of harmful gut bacteria can interfere with brain development and may contribute to autism. Strategies to improve the gut microflora profile through dietary modification may help to alleviate gut disorders in autistic patients. Sixty young male western albino rats were divided into six equal groups. The first group served as the control; the second group was given an oral neurotoxic dose of propionic (PPA) (250 mg/kg body weight/day) for three days. The third group received an orogastric dose of ampicillin (50 mg/kg for three weeks) with a standard diet. Groups 4, 5 and 6 were given an orogastric dose of ampicillin and fed high-carbohydrate, high-protein and high-lipid diets, respectively, for 10 weeks. Biochemical parameters related to oxidative stress were investigated in brain homogenates from each group. The microbiology results revealed descriptive changes in the fecal microbiota of rats treated with ampicillin either alone or with the three dietary regimens. The results of PPA acid and ampicillin treatment showed significant increases in lipid peroxidation and catalase with decreases in glutathione and potassium compared with levels in the control group. A protein-rich diet was effective at restoring the glutathione level, while the carbohydrate-rich diet recovered lipid peroxidation and catalase activity. In addition, the three dietary regimens significantly increase the potassium level in the brain tissue of the test animals. Lactate dehydrogenase was remarkably elevated in all groups relative to the control. No outstanding effects were observed in glutathione S-transferase and creatine kinase. The changes observed in the measured parameters reflect the neurotoxic effects of PPA and ampicillin. Lipid peroxide and catalase activity and the levels of glutathione and potassium are satisfactory biomarkers of PPA and ampicillin neurotoxicity. Based on the effects of the three dietary regimens, a balanced diet can protect against PPA or ampicillin-induced neurotoxicity that might induce autistic traits. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder that has recently been associated with PPA neurotoxicity.
    Gut Pathogens 01/2015; 7:7. DOI:10.1186/s13099-015-0054-4 · 2.07 Impact Factor
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    ABSTRACT: Prebiotics are non-digestible food ingredients (oligosaccharides) that reach the colon and are used as substrate by microorganisms producing energy, metabolites and micronutrients used for the host; in addition they also stimulate the selective growth of certain beneficial species (mainly bifidobacteria and lactobacilli) in the intestinal microbiota. In this article, a multidisciplinary approach to understand the concept of prebiotic carbohydrates, their properties and beneficial effects in humans has been carried out. Definitions of prebiotics, reported by relevant international organizations and researchers, are described. A comprehensive description of accepted prebiotics having strong scientific evidence of their beneficial properties in humans (inulin-type fructans, FOS, GOS, lactulose and human milk oligosaccharides) is reported. Emerging prebiotics and those which are in the early stages of study have also included in this study. Taken into account that the chemical structure greatly influences carbohydrates prebiotic properties, the analytical techniques used for their analysis and characterization are discussed. In vitro and in vivo models used to evaluate the gastrointestinal digestion, absorption resistance and fermentability in the colon of prebiotics as well as major criteria to design robust intervention trials in humans are described. Finally, a comprehensive summary of the beneficial effects of prebiotics for health at systemic and intestinal levels is reported. The research effort on prebiotics has been intensive in last decades and has demonstrated that a multidisciplinary approach is necessary in order to claim their health benefits. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.


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