HHS Public access Author manuscript Science Author manuscript; available in PMC 2018 November 18 Published in final edited form as Science2018May18,360(6390):795-800.do1:10.1126 scIence. aaq0926 Gut microbiota utilize immunoglobulin A for mucosal colonization G.P. Donaldson,, M.S. Ladinsky, K.B. Yu1, J.G.Sanders, B.B. Yoo, W.C. Chou,ME Conner, A.M. Earl3, R. Knight2, P.J. Bjorkman, and S.K.Mazmanian Department of Biology and Biological Engineering, California Institute of Technology, Pasadena CA 91125 USA Deparment of Pediatrics, University of California, San Diego, California, 92110: Department of Computer Science and Engineering, University of California, San Diego, California, USA 92093 Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030.USA Abstract The immune system responds vigorously to microbial infection, while permitting life-long colonization by the microbiome. Mechanisms that facilitate the establishment and stability of th gut microbiota remain poorly described. We discovered that a sensor/regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA). Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo The IgA response was required for B. fragilis, and other commensal species, to occupy a defined mucosal niche that mediated stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that igA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis Main Text At birth, ecological and evolutionary processes commence to assemble a complex microbial consortium in the animal gut. Community composition of the adult human gut microbiome is remarkably stable during health, despite day-to-day variability in diet and diverse environmental exposures. Instability, or dysbiosis, may be involved in the etiology of a variety of immune, metabolic, and neurologic diseases(1, 2). Longitudinal sequencing udies indicate a majority of bacterial strains persist within an individual for years(3), and for most species there is a single, persistently dominant strain(4)(termed"single-strain stability ) Mucus and components of the innate and adaptive immune systems are thought to influence microbiome stability, independently of diet. For example, immunoglobulin A Correspondence to: donalds(@caltech.edu and sarkis @caltech. edu.Gut microbiota utilize immunoglobulin A for mucosal colonization G.P. Donaldson1,* , M.S. Ladinsky1, K.B. Yu1, J.G. Sanders2, B.B. Yoo1, W.C. Chou3, M.E. Conner4, A.M. Earl3, R. Knight2, P.J. Bjorkman1, and S.K. Mazmanian1,* 1Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA 2Deparment of Pediatrics, University of California, San Diego, California, 92110; Department of Computer Science and Engineering, University of California, San Diego, California, USA 92093 3 Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA 4Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA Abstract The immune system responds vigorously to microbial infection, while permitting life-long colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We discovered that a sensor/regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA). Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis, and other commensal species, to occupy a defined mucosal niche that mediated stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Main Text At birth, ecological and evolutionary processes commence to assemble a complex microbial consortium in the animal gut. Community composition of the adult human gut microbiome is remarkably stable during health, despite day-to-day variability in diet and diverse environmental exposures. Instability, or dysbiosis, may be involved in the etiology of a variety of immune, metabolic, and neurologic diseases (1, 2). Longitudinal sequencing studies indicate a majority of bacterial strains persist within an individual for years (3), and for most species there is a single, persistently dominant strain (4) (termed “single-strain stability”). Mucus and components of the innate and adaptive immune systems are thought to influence microbiome stability, independently of diet. For example, immunoglobulin A *Correspondence to: gdonalds@caltech.edu and sarkis@caltech.edu. HHS Public Access Author manuscript Science. Author manuscript; available in PMC 2018 November 18. Published in final edited form as: Science. 2018 May 18; 360(6390): 795–800. doi:10.1126/science.aaq0926. Author Manuscript Author Manuscript Author Manuscript Author Manuscript