Microbiota-Targeted Therapies: An Ecological Perspective

被引:194
作者
Lemon, Katherine P. [1 ,2 ]
Armitage, Gary C. [3 ]
Relman, David A. [4 ,5 ,6 ]
Fischbach, Michael A. [7 ,8 ]
机构
[1] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA
[2] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA
[3] Univ Calif San Francisco, Sch Dent, Div Periodontol, San Francisco, CA 94143 USA
[4] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[5] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA
[6] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
[7] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA
[8] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA
关键词
INFLUENZAE TYPE-B; ANTIBIOTIC-ASSOCIATED DIARRHEA; CLINICAL-PRACTICE GUIDELINES; INFECTIOUS-DISEASES SOCIETY; STAPHYLOCOCCUS-AUREUS; GUT MICROBIOTA; CHILDREN; PROBIOTICS; CARRIAGE; AGE;
D O I
10.1126/scitranslmed.3004183
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. 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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页数:8
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