Microbial Ecology in States of Health and Disease Workshop Summary (2014) / Chapter Skim
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A10 Microbiota-targeted therapies: An ecological perspective--Katherine P. Lemon, Gary C. Armitage, David A. Relman, and Michael Fischbach
A10 Microbiota-targeted therapies: An ecological perspective--Katherine P. Lemon, Gary C. Armitage, David A. Relman, and Michael Fischbach
Pages 273-291
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35 Department of Molecular Genetics, The Forsyth Institute, Cambridge, MA 02142, USA. 36 Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
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Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic.
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. Although the relationship between beta diversity and health is not as well explored, the example of cystic fibrosis is instructive: Increased beta diversity is observed in later-stage disease after the oropharyngeal microbiota is invaded by Pseudomonas aeruginosa and subjected to increased antibiotic
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Antibacterial conjugate vaccines represent the simplest perturbations; these agents stimulate the immune system to remove specific strains of a single species from the community. Fecal transplantation, which lies at the opposite end of the spectrum, consists of a colonic lavage to dislodge the resident community followed by the infusion of a donor community (20 to 30 g of donor feces suspended in 100 ml of water)
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Two examples of such vaccines are conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae that protect against infection and clear or prevent colonization (Figure A10-1A)
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Can clinically useful adjunctive therapies be developed to prevent secondary infections?
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microbiota that normally check the growth of pathogens, a secondary infection can ensue. Repopulating antibiotictreated patients with probiotics is a promising strategy to prevent secondary infections.
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. The ball containing the network represents the microbial community, and the shift in its horizontal position within the landscape represents movement between alternative stable states.
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. In both cases, there is a strong need for large randomized controlled trials with a consensus definition of the disease state and clinical endpoints, and standardized probiotic constituents and dosing.
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? In addition to providing equally effective treatment of susceptible bacterial pathogens, narrow-spectrum antibiotics minimize the collateral damage to microbiota community structure, decrease the selective pressure for the spread of antibiotic resistance genes within the microbiota, and lower the probability of acquiring resistant strains.
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. Numerous infections are caused by bacteria living in biofilms: These include dental caries, periodontal infections, otitis media, endocarditis, osteomyelitis, artificial joint infections, pulmonary infections in cystic fibrosis, and device-associated infections (Darouiche, 2004; Furukawa et al., 2006)
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. The widespread clinical use of probiotics will require proof of efficacy and safety from large randomized controlled trials with a consensus definition of the disease state, pharmaceutical-grade products, and standardized dosing (Cohen et al., 2010; Johnston et al., 2011; Thomas and Greer, 2010)
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Notably, a probiotic does not need to cause a change in the composition of the community to exert an effect, because community function (or that of the host) may be altered without changing community membership.
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, NIH DE020751 (K.P.L.) , a Children's Hospital Boston, Office of Faculty Development Career Development Fellowship (K.P.L.)
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Kolter, Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseu domonas aeruginosa. Environ.
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H Wilcox; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America, Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA)
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T Swanson; Pediatric Infectious Diseases Society and the Infectious Diseases Society of America, Executive summary: The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.
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Bulsara, Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 125, 921–930 (2010)
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