Targeting the Human Microbiome With Antibiotics, Probiotics, and Prebiotics: Gastroenterology Enters the Metagenomics Era

Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA.
Gastroenterology (Impact Factor: 16.72). 06/2009; 136(6):2015-31. DOI: 10.1053/j.gastro.2009.01.072
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Studies of metagenomics and the human microbiome will tremendously expand our knowledge of the composition of microbial communities in the human body. As our understanding of microbial variation and corresponding genetic parameters is refined, this information can be applied to rational remodeling or "tailoring" of human-associated microbial communities and their associated functions. Physiologic features such as the development of innate and adaptive immunity, relative susceptibilities to infections, immune tolerance, bioavailability of nutrients, and intestinal barrier function may be modified by changing the composition and functions of the microbial communities. The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the rational deployment of antibiotics, probiotics, and prebiotics. Antibiotics might be used to remove or suppress undesirable components of the human microbiome. Probiotics can introduce missing microbial components with known beneficial functions for the human host. Prebiotics can enhance the proliferation of beneficial microbes or probiotics, to maximize sustainable changes in the human microbiome. Combinations of these approaches might provide synergistic and effective therapies for specific disorders. The human microbiome could be manipulated by such "smart" strategies to prevent and treat acute gastroenteritis, antibiotic-associated diarrhea and colitis, inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and a variety of other disorders.

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    • "Manipulation of the microbiota with rationally selected pre-or probiotics can inhibit pathogens, strengthen epithelial barrier functions and supply the host with key nutrients (e.g. vitamins) [7]. Despite these claimed health benefits, it has also to be cautioned that certain safety aspects should be taken into account when using probiotics: taxonomic identification of the probiotic strain is necessary to avoid pathogenicity, as well as inhibiting the risk of infection and antimicrobial resistance [8]. "
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    ABSTRACT: To date, the precise role of the human microbiome in health and disease states remains largely undefined. Complex and selective crosstalk systems between the microbiome and mammalian cells are also not yet reported. Research up till now mainly focused on bacterial synthesis of virulence factors, reactive oxygen/nitrogen species (ROS/RNS) and hydrogen sulphide, as well as on the activation of exogenous mutagen precursors by intestinal bacteria. We discovered that certain quorum sensing peptides, produced by bacteria, interact with mammalian cells, in casu cancer cells: Phr0662 (Bacillus sp.), EntF-metabolite (Enterococcus faecium) and EDF-derived (Escherichia coli) peptides initiate HCT-8/E11 colon cancer cell invasion, with Phr0662 also promoting angiogenesis. Our findings thus indicate that the human microbiome, through their quorum sensing peptides, may be one of the factors responsible for cancer metastasis. Copyright © 2015. Published by Elsevier Inc.
    Peptides 01/2015; 64. DOI:10.1016/j.peptides.2014.12.009 · 2.62 Impact Factor
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    • "Another interesting finding of the David et al. (2014) study was that foodborne microbes transiently colonized the gut, introducing the idea that food may not only select for commensal bacterial species, but serve as a reservoir for new microbial introductions. Intentional introduction of food-borne microorganisms (probiotics) as well as prebiotic food ingredients and foods high in fiber can also be a means of subtly changing the relative abundance of bacterial species in the gut (Preidis and Versalovic, 2009). Thus, despite the inherent stability of the microbiome over time, changes related to weight loss and diet composition continue to subtly alter the composition and relative abundance of our commensal organisms, driving the development of our gut microbiome throughout adulthood. "
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    ABSTRACT: The important role of the gut microbiome in maintaining human health has necessitated a better understanding of the temporal dynamics of intestinal microbial communities as well as the host and environmental factors driving these dynamics. Genetics, mode of birth, infant feeding patterns, antibiotic usage, sanitary living conditions and long term dietary habits contribute to shaping the composition of the gut microbiome. This review focuses primarily on diet, as it is one of the most pivotal factors in the development of the human gut microbiome from infancy to the elderly. The infant gut microbiota is characterized by a high degree of instability, only reaching a state similar to that of adults by 2-3 years of age; consistent with the establishment of a varied solid food diet. The diet-related factors influencing the development of the infant gut microbiome include whether the child is breast or formula-fed as well as how and when solid foods are introduced. In contrast to the infant gut, the adult gut microbiome is resilient to large shifts in community structure. Several studies have shown that dietary changes induce transient fluctuations in the adult microbiome, sometimes in as little as 24 hours; however, the microbial community rapidly returns to its stable state. Current knowledge of how long-term dietary habits shape the gut microbiome is limited by the lack of long-term feeding studies coupled with temporal gut microbiota characterization. However, long-term weight loss studies have been shown to alter the ratio of the Bacteriodetes and Firmicutes, the two major bacterial phyla residing in the human gastrointestinal tract. With ageing, diet-related factors such as malnutrition are associated with microbiome shifts, although the cause and effect relationship between these factors has not been established. Increased pharmaceutical usage is also more prevalent in the elderly and can contribute to reduced gut microbiota stability and diversity. Foods con
    Frontiers in Microbiology 09/2014; 5:494. DOI:10.3389/fmicb.2014.00494 · 3.99 Impact Factor
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    • "This community encompasses trillions of bacteria with an estimated biomass of 1 kg [5]. Molecular and metagenomic approaches have allowed identifying the main bacterial communities present in the digestive tract, their role in health, and their relationships with specific diseases [6] [7] [8]. "
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    ABSTRACT: A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.
    Research Journal of Immunology 07/2014; 2014:8. DOI:10.1155/2014/586939
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