In their intestine, humans possess an "extended genome" of millions of microbial genes-the microbiome. Because this complex symbiosis influences host metabolism, physiology, and gene expression, it has been proposed that humans are complex biologic "superorganisms." Advances in microbiologic analysis and systems biology are now beginning to implicate the gut microbiome in the etiology of localized intestinal diseases such as the irritable bowel syndrome, inflammatory bowel disease, and colon cancer. These approaches also suggest possible links between the gut and previously unassociated systemic conditions such as type 2 diabetes and obesity. The elucidation of the intestinal microbiome is therefore likely to underpin future disease prevention strategies, personalized health care regimens, and the development of novel therapeutic interventions. This review summarizes the research that is defining our understanding of the intestinal microbiome and highlights future areas of research in gastroenterology and human health in which the intestinal microbiome will play a significant role.
"In the study, it was demonstrated that several metabolic biomarkers could be connected to human host and gut microbial co-metabolism. Other studies have identified metabolites as biomarkers for the evaluation of disease risks , . Our approach will be particularly helpful in tackling questions regarding the interplay of host-microbial co-metabolism by predicting the synthesis routes of measured metabolites, assigning plausible enzyme reactions and enzymes to mammalian cells and/or gut microbes. "
[Show abstract][Hide abstract] ABSTRACT: The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.
PLoS ONE 01/2014; 9(1):e84769. DOI:10.1371/journal.pone.0084769 · 3.23 Impact Factor
"The hologenome theory considers that the holobiont, an organism and all of its associated symbiotic microbes, including parasites, mutualists, synergists, and amensalists as a result of symbiopoiesis, or codevelopment of the host and symbiont (Margulis and Fester, 1991; Rohwer et al., 2009; Gilbert et al., 2010; Rosenberg and Zilber-Rosenberg, 2011). This evolutionary approach that considers any organism as a result of integration with microorganisms has many implications and it is related to the Bioma Depletion Theory (also called “hygiene hypothesis”) that considers that humans (and all mammals) and their microbiome evolved as a “superorganism” (Kinross et al., 2008; Rook, 2009). The immune system can be seen as having evolved as an interface with symbiotic organisms more than as a defense against invading organisms. "
[Show abstract][Hide abstract] ABSTRACT: The acceptance of Darwin's theory of evolution by natural selection is not complete and it has been pointed out its limitation to explain the complex processes that constitute the transformation of species. The darwinian paradigm had its origin in the free market theories and concepts of Malthus and Spencer. Nature was explained on the basis of market theories moving away from an accurate explanation of natural phenomena. It is common that new discoveries bring about contradictions that are intended to be overcome by adjusting results to the dominant reductionist paradigm using all sorts of gradations and combinations that are admitted for each case. Modern findings represent a challenge to the interpretation of the observations with the Darwinian view of competition and struggle for life as theoretical basis. New holistic interpretations are emerging related with the Net of Life, in which the interconnection of ecosystems constitutes a dynamic and self-regulating biosphere: Viruses are recognized as a macroorganism with a huge collection of genes, most unknown, that constitute the major planet's gene pool with a fundamental role in evolution. The hologenome theory considers an organism and all of its associated symbiotic microbes as a result of symbiopoiesis. Microbes, helmints, that normally are understood as parasites, are cohabitants and they have cohabited with their host and drives the evolution and existence of the partners. Each organism is a result of integration of complex systems. The eukaryotic organism is the result of combination of bacterial, virus and eukaryotic DNA and the interaction of its own genome with the genome of its microbiota resulting in an intertwined metabolism (a “superorganism”) along evolution. These new interpretations are remarkable points to be considered in order to construct a solid theory adjusted to the facts and with less speculations and tortuous semantic traps.
Frontiers in Cellular and Infection Microbiology 05/2012; 2:54. DOI:10.3389/fcimb.2012.00054 · 3.72 Impact Factor
"The human intestine provides residence to 1×1013 bacteria, which is ten-fold higher than the total number of cells in the human body (1×1012), and contains a genome with 100-fold more genes than that of humans , . These bacteria represent an integral component of the human body, and a dynamic contributor to systems biology. "
[Show abstract][Hide abstract] ABSTRACT: Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in liver and is able to transport bile acids (BAs) in vitro. Male Oatp1a1-null mice have increased concentrations of taurodeoxycholic acid (TDCA), a secondary BA generated by intestinal bacteria, in both serum and livers. Therefore, in the present study, BA concentrations and intestinal bacteria in wild-type (WT) and Oatp1a1-null mice were quantified to investigate whether the increase of secondary BAs in Oatp1a1-null mice is due to alterations in intestinal bacteria. The data demonstrate that Oatp1a1-null mice : (1) have similar bile flow and BA concentrations in bile as WT mice; (2) have a markedly different BA composition in the intestinal contents, with a decrease in conjugated BAs and an increase in unconjugated BAs; (3) have BAs in the feces that are more deconjugated, desulfated, 7-dehydroxylated, 3-epimerized, and oxidized, but less 7-epimerized; (4) have 10-fold more bacteria in the small intestine, and 2-fold more bacteria in the large intestine which is majorly due to a 200% increase in Bacteroides and a 30% reduction in Firmicutes; and (5) have a different urinary excretion of bacteria-related metabolites than WT mice. In conclusion, the present study for the first time established that lack of a liver transporter (Oatp1a1) markedly alters the intestinal environment in mice, namely the bacteria composition.
PLoS ONE 04/2012; 7(4):e34522. DOI:10.1371/journal.pone.0034522 · 3.23 Impact Factor
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