The Intestinal Environment in Health and Disease – Recent Insights on the Potential of Intestinal Bacteria to Influence Human Health

Laboratory of Microbial Ecology and Technology, Ghent University, Belgium.
Current pharmaceutical design (Impact Factor: 3.45). 02/2009; 15(18):2051-65. DOI: 10.2174/138161209788489159
Source: PubMed


The human intestine is colonized by a complex microbial ecosystem, which could be considered as a separate organ within the human host, having a coding capacity which exceeds the liver by a factor 100. On the one hand, this extensive microbiome is closely involved in the first-pass metabolism and bioavailability of food and drug compounds. Understanding to which extent each individual's gut microbiota affects the bioavailability and response to orally administered drugs is therefore a first important challenge towards novel drug development strategies. On the other hand, as our microbiota is directly or indirectly involved in the onset of a number of disease states, a new generation of therapeutics may be developed that affect the structure and functioning of the intestinal microbiota and interfere with their specific cross-talk with the human host. Ultimately, the intestinal microbiota may even be used as a biomarker for impending diseases inside or outside the gastrointestinal tract and for the evaluation of responses to specific therapeutic interventions. This review will therefore highlight the importance of the indigenous microbial community and its enormous metabolic potential, microbe-microbe interactions, mechanisms of host-bacterium cross-talk and will discuss the onset of obesity, a specific disease state in which the role of intestinal bacteria becomes more and more apparent. Understanding the importance of the intestinal ecosystem in these phenomena may open the door for new strategies which target the management of the intestinal microbiome into the desired direction and therefore to a completely new type of nutrition research and pharmaceutical design.

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    • "The OLAND mixed communities form a one-stage sustainable nitrogen removal process removing ammonia from wastewaters with a low C/N ratio and ammonia loaded gas streams through a combination of partial nitritation and anammox [28], [33], [34]. Finally, the fecal microbiome opens perspective for pre- and probiotics testing and fecal transplantations [4]–[6]. "
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    ABSTRACT: The use of mixed microbial communities (microbiomes) for biotechnological applications has steadily increased over the past decades. However, these microbiomes are not readily available from public culture collections, hampering their potential for widespread use. The main reason for this lack of availability is the lack of an effective cryopreservation protocol. Due to this critical need, we evaluated the functionality as well as the community structure of three different types of microbiomes before and after cryopreservation with two cryoprotective agents (CPA). Microbiomes were selected based upon relevance towards applications: (1) a methanotrophic co-culture (MOB), with potential for mitigation of greenhouse gas emissions, environmental pollutants removal and bioplastics production; (2) an oxygen limited autotrophic nitrification/denitrification (OLAND) biofilm, with enhanced economic and ecological benefits for wastewater treatment, and (3) fecal material from a human donor, with potential applications for fecal transplants and pre/probiotics research. After three months of cryopreservation at -80°C, we found that metabolic activity, in terms of the specific activity recovery of MOB, aerobic ammonium oxidizing bacteria (AerAOB) and anaerobic AOB (AnAOB, anammox) in the OLAND mixed culture, resumes sooner when one of our selected CPA [dimethyl sulfoxide (DMSO) and DMSO plus trehalose and tryptic soy broth (DMSO+TT)] was added. However, the activity of the fecal community was not influenced by the CPA addition, although the preservation of the community structure (as determined by 16S rRNA gene sequencing) was enhanced by addition of CPA. In summary, we have evaluated a cryopreservation protocol that succeeded in preserving both community structure and functionality of value-added microbiomes. This will allow individual laboratories and culture collections to boost the use of microbiomes in biotechnological applications.
    PLoS ONE 06/2014; 9(6):e99517. DOI:10.1371/journal.pone.0099517 · 3.23 Impact Factor
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    • "However, the possibility of understanding the mechanism of action of these ingredients in the different areas of the gastrointestinal tract (GIT) is frequently limited due to clear sampling issues (Marzorati et al. 2009). In this respect, the application of well-designed in vitro continuous models of the GIT may represent a useful complementary tool to study the intestinal microbial processes in terms of gastrointestinal resource management (GRM), i.e. the management of the complex gut microbiota and its metabolism with the aim of improving the host health (Manning and Gibson 2004; Gibson et al. 2004; Possemiers et al. 2009). We made use of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME Ò ) to assess the effect of two blends of a commercially available plant-polysaccharide supplement—Ambrotose "
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    ABSTRACT: The combination of a Simulator of the Human Intestinal Microbial Ecosystem with ad hoc molecular techniques (i.e. pyrosequencing, denaturing gradient gel electrophoresis and quantitative PCR) allowed an evaluation of the extent to which two plant polysaccharide supplements could modify a complex gut microbial community. The presence of Aloe vera gel powder and algae extract in product B as compared to the standard blend (product A) improved its fermentation along the entire simulated colon. The potential extended effect of product B in the simulated distal colon, as compared to product A, was confirmed by: (i) the separate clustering of the samples before and after the treatment in the phylogenetic-based dendrogram and OTU-based PCoA plot only for product B; (ii) a higher richness estimator (+33 vs. -36 % of product A); and (iii) a higher dynamic parameter (21 vs. 13 %). These data show that the combination of well designed in vitro simulators with barcoded pyrosequencing is a powerful tool for characterizing changes occurring in the gut microbiota following a treatment. However, for the quantification of low-abundance species-of interest because of their relationship to potential positive health effects (i.e. bifidobacteria or lactobacilli)-conventional molecular ecological approaches, such as PCR-DGGE and qPCR, still remain a very useful complementary tool.
    Antonie van Leeuwenhoek 10/2012; 103(2). DOI:10.1007/s10482-012-9821-0 · 1.81 Impact Factor
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    • "The above examples underscore the reasons recent reviews in the pharmacology literature have articulated the need for future drug development to include an integrated assessment of host and environmental factors , including gut microbes that affect drug disposition (Grundmann 2010; Sousa et al. 2008; Wilson 2009; Wilson and Nicholson 2009). This topic has received little attention in the toxicology literature (Possemiers et al. 2009). In this regard, pharmaco metabolomics appears to be an important emerging tool for investigating how gut ecology may affect the fate of chemical toxicants and their contribution to diabetes and obesity risk. "
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    ABSTRACT: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans.
    Environmental Health Perspectives 03/2012; 120(3):332-9. DOI:10.1289/ehp.1104204 · 7.98 Impact Factor
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