The intestinal microbiota and viral susceptibility

Perspective Article published: 27 April 2011 doi: 10.3389/fmicb.2011.00092 The intestinal microbiota and viral susceptibility Julie K. Pfeiffer 1* and Justin L. Sonnenburg 2* 1 2 Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA Edited by: Peter J. Turnbaugh, Harvard University, USA Reviewed by: Alain Stintzi, Ottawa Institute of Systems Biology, Canada Dennis L. Kasper, Harvard Medical School, USA *Correspondence: Julie K. Pfeiffer, Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9048, USA. e-mail: julie.pfeiffer@utsouthwestern. edu; Justin L. Sonnenburg, Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305-5124, USA. e-mail: Many infections start with microbial invasion of mucosal surfaces, which are typically colonized by a community of resident microbes. A growing body of literature demonstrates that the resident microbiota plays a significant role in host susceptibility to pathogens. Recent work has largely focused on the considerable effect that the intestinal microbiota can have upon bacterial pathogenesis. These studies reveal many significant gaps in our knowledge about the mechanisms by which the resident community impacts pathogen invasion and the nature of the ensuing host immune response. It is likely that as viral pathogens become the focus of studies that examine microbiota–host interaction, substantial effects of resident communities exerted via diverse mechanisms will be elucidated. Here we provide a perspective of the exciting emerging field that examines how the intestinal microbiota influences host susceptibility to viruses. Keywords: intestinal microbiota, virus, pathogen, mucosal immune system, infection The intestinal microbiota A staggering number of microbes reside in and upon the human body (Dethlefsen et al., 2007). Our co-evolution with this microbiota has resulted in the integration of microbially derived developmental cues and metabolic capacities into human biology (Backhed et al., 2005). The vast majority of the 10–100 trillion microbial cells that inhabit the human body are found within the distal digestive tract. An altered intestinal microbiota composition has been linked to numerous pathologic states such as inflammatory bowel diseases and obesity in mouse models and in humans (Ley et al., 2005, 2006; Frank et al., 2007). In some cases an etiological relationship between the microbiota and disease state has been established (Turnbaugh et al., 2006; Garrett et al., 2007; Vijay-Kumar et al., 2010). Thus, human biology and health are intimately intertwined with the biology of our microbial inhabitants. Ongoing large-scale sequencing efforts are providing a comprehensive sequence-based definition of this intestinal microbiota (Qin et al., 2010). Typically two bacterial phyla dominate the healthy Western adult intestine, the Firmicutes and Bacteroidetes compose >90% of the bacterial cells. Proteobacterium and Bifidobacterium and a handful of other bacterial phyla make up the remainder of the community, along with members of Archaea and Eukaryota. Despite the limited representation of bacterial phyla, at finer scales of phylogenetic resolution, such as species and strain, the intestinal microbiota is highly diverse and exhibits substantial compositional variability between people, and thus represents an “individualized fingerprint.” In addition to inter-individual variability, the microbiota exhibits temporal variability, likely due to the numerous factors that continually perturb this dynamic microbial ecosystem, such as changes in host diet and introduction of orally acquired pathogens. www.frontiersin.org The tremendous foundation of microbiome sequencing data is propelling human microbiota studies into a second phase focused on function and mechanism. Recently published metagenomic data highlight the overlap and conservation of core functionalities within the intestinal microbiome of different individuals (Turnbaugh et al., 2007, 2009). This similarity embedded within the combined genomes of different consortia reveals that each person’s gut is endowed with a core set of genes (a core microbiome) that carry out functions common to the human intestine. This new phase of investigation, which is focused on the emergent properties of the host–microbial super-organism, is attracting biomedical scientists from diverse fields, including virologists. A well-supported case for microbiota impact on pathogen susceptibility The ability of an orally acquired pathogen to cause disease is dependant upon multiple steps that the microbiota may influence. A pathogen must navigate through the dense community of microbes, gain access to the epithelial surface, and manage the ensuing immune response. Commensal microbes present significant competition for nutrients (Sonnenburg et al., 2006), secrete microbicidal proteins (Corr et al., 2007), and elicit host responses that are fundamental to the development and maintenance of the mucosal innate and adaptive immune system (Cebra, 1999; Hooper et al., 2001; Ivanov et al., 2009). Despite this seemingly inhospitable environment, pathogens can gain access to host tissue and cause disease. The role of the intestinal microbiota in reducing host susceptibility to enteric bacterial pathogens is commonly referred to as “colonization resistance,” although the underlying mechanisms are poorly April 2011 | Volume 2 | Article 92 | 1 Pfeiffer and Sonnenburg understood. The increased susceptibility of oral antibiotic-treated mice or humans to enteric infection nicely illustrates the potential impact of microbiota perturbation on pathogen emergence (Pavia et al., 1990; Barthel et al., 2003; Doorduyn et al., 2006; Lawley et al., 2009). Furthermore, treating infectious diarrheas with live microbial supplements (i.e., probiotics) has proven successful in decreasing the duration of symptoms, but the mechanisms of action and whether such treatment is more effective for certain causative agents (e.g., bacterial vs. viral) remain obscure (Servin, 2004; Vandenplas et al., 2007; Guandalini, 2008; Allen et al., 2010). Together, these data support that alterations in host-associated microbial communities can impact an ensuing interaction with a pathogen. Intestinal microbiota influences immune function and pathogen susceptibility The gut microbiota influences the status of the host immune system during development and throughout life. The host typically maintains a dynamic and attenuated physiological state of inflammation in the mucosa that is tuned to the membership of the adjacent microbial community (Cebra, 1999). Disruption of the microbiotadependent homeostasis can be deleterious to the host. 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