Contribution of Interkingdom Signaling to the Human Microbiome

Microbiologists like to quote the statistic that there are ten times as many microbial cells as human cells in the human body as a way of illustrating the importance of microbes to our overall physiology. However, any effects that our microbial inhabitants elicit on human biology are very poorly understood. One approach to increasing our understanding of host-microbe interactions is the Human Microbiome Project (HMP), which was recently initiated by the National Institutes of Health to elucidate the influence of microbes on human development, physiology, immunity, and nutrition. The mission of the HMP is to generate resources that enable the "comprehensive characterization of the human microbiota and analysis of its role in human health and disease" ( Among the specific goals of the HMP are to determine whether individuals share a core human microbiome and, if so, to understand whether changes in the human microbiome can be correlated with changes in human health. Apart from raising awareness of the contributions of microbes to human development and health, these studies should introduce novel technologies for studying these interactions. For example, systems biology

A. Jahoor

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6540, Lubbock, TX 79430, USA e-mail: [email protected]

S. Williams

Associate Professor, Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6540, Lubbock, TX 79430, USA e-mail: [email protected]

Department of Surgery, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, Texas, 79430, USA e-mail: [email protected]

M. Lyte and P.P.E. Freestone (eds.), Microbial Endocrinology, Interkingdom Signaling in Infectious Disease and Health,

DOI 10.1007/978-1-4419-5576-0_14, © Springer Science+Business Media, LLC 2010

Fig. 14.1 The microbiome is composed of the microflora and transient microbes dwelling in the human host. Interkingdom signaling, or small chemical cell-to-cell signal exchanges, between microbes and their hosts may contribute to the function or dysfunction or of the human microbiome

approaches to understanding the microbiome, such as meta-genomic analyses, should reveal new and potentially instructive microbial/host interactions.

We propose that interkingdom signaling between microbes and their hosts is a process essential to a functional and/or dysfunctional or diseased microbiome (Fig. 14.1). The term interkingdom signaling refers to the concept that signaling molecules produced by organisms from every kingdom of nature can participate in cross-talk, communication, or signal interference across kingdom boundaries. This term was coined independently by two different groups to describe the effects of quorum sensing auto-inducers from Gram-negative bacteria on mammalian host cells (Williams et al. 2004; Shiner et al. 2005a, b; Rumbaugh 2007), and to describe the effects of mammalian hormones on the QS systems of bacteria (Sperandio et al. 2003). Here, we use the term interkingdom signaling or IKS to describe the ability of small microbial chemicals to affect signaling cascades and elicit specific cellular responses in host cells.

There are several well-explored examples of microbial products that modulate cell signaling in host cells, the majority of which are mediated via host toll-like receptors (TLRs), which recognize the microbial products as pathogen-associated molecular patterns (PAMPs) (Iwasaki and Medzhitov 2004). Common PAMPs include microbial effectors, such as lipopolysaccharides, peptidoglycan, and flagel-lin, which are generally potent regulators of host immune responses. The IKS concept suggests that other, more subtle signals mediated by small soluble and/or volatile chemicals produced by microbes may also utilize host receptors to mediate interactions that may be beneficial to one or both participants in the interaction.

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