Metabolites: messengers between the microbiota and the immune system

Abstract

The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases.The mammalian intestine harbors a dense and complex microbial community, termed the microbiota. The commensal microbiome and, in particular, the dense and diverse microbial community inhabiting the gastrointestinal tract play a pivotal role in the maintenance of organismal homeostasis and stable physiology. Research over the last decade has highlighted the concept that the eukaryotic host and its microbiota, rather than existing in isolation, compose a complex meta-organism termed the "holobiont," jointly regulating multiple aspects of mammalian physiology, including immune system development, metabolism, and nervous system function (Sommer and Backhed 2013). The interaction between the microbiota and the host is most prominent at mucosal surfaces, which provide an interface between the mostly microbe-free host, the microbiota, and the environment. At the same time, the presence of the microbial community within the eukaryotic host necessitates the development of a sophisticated immune system that controls and maintains a beneficial symbiosis of the holobiont through the continuous communication between the microbiome and the host.

Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System

“…Acetate (C2), propionate (C3) and butyrate (C4) are by far the most abundant of the intestinal SCFAs (Cummings et al, 1987; Morrison and Preston, 2016). Members of the Bacteroidetes provide most of the acetate and propionate whereas Firmicutes, which tend to utilize polysaccharides less efficiently, are believed to be the primary producers of butyrate (Flint et al, 2015; Kaoutari et al, 2013; Levy et al, 2016; Louis et al, 2010). While a comprehensive species inventory of SCFA producers remains elusive, studies investigating individual species have uncovered interesting microbial cross-feeding dynamics (recently reviewed by (Flint et al, 2015) and (Ríos-Covián et al, 2016)).…”

The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation

“…There are extensive bidirectional interactions between the host and its microbiota, and it is well recognized that immune system activity is strongly influenced by commensal bacteria (Brown and Clarke, 2016; Levy et al, 2016; Thaiss et al, 2016). While it is intuitive that bacteria in the gut would impact mucosal immune responses, the ability of gut microbes to impact immune activity in different sites, such as the bone marrow, spleen, or lungs, is less intuitive.…”

“…While it is intuitive that bacteria in the gut would impact mucosal immune responses, the ability of gut microbes to impact immune activity in different sites, such as the bone marrow, spleen, or lungs, is less intuitive. However, an increasing number of studies demonstrate the far reaching impact of commensal microbes on immune system activity throughout the body (Brown and Clarke, 2016; Levy et al, 2016). Thus, it was determined whether stressor-induced changes in the composition of the gut microbiota were also associated with stressor-induced immunomodulation.…”

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

“…) and bacteria predominate in the mass production of metabolites known to have immune and other effects (Levy et al. ; Postler and Ghosh ). Conversely, the functional impact of eukaryotic microbes has primarily been detected in cases of active pathogenicity.…”