A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors

Abstract

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system.

Keywords: Cytokines; Endocrine system; Gut-brain axis; Immune system; Lipopolysaccharide; Microbiome; Social behavior.

Figure 1

Previous work has been aimed at determining the role that the central nervous system, the gut microbiome and the immune systems play in social behavior and adult sensitivity to subsequent stressors, yet some previous studies have overlooked the interactions between these systems and the communication among the systems used to regulate (or deregulate) social behavior. This theoretical model illustrates some of the brain-gut-immune interactions that play a role in behavioral outcomes, including social and affective behaviors (e.g., investigation, aggression, and anxiety- and depression-like behavior). The interactions among these systems are key to understanding how social behavioral changes occur and the potential mechanisms mediating psychopathologies.

Figure 2

The microbial community composition in fecal samples of male and female hamsters across treatment groups. The composition of the male and female gut microbiome is made up of 14 phyla, including one phylum from the Archaea kingdom and a designated ‘Other’ category where no specific organism was found after 16s rRNA sequencing on the Illumina MiSeq platform. Both the male and female gut microbiome in Siberian hamsters is dominated by Firmicutes and Bacteroidetes, yet antibiotic treatment did not affect these highly abundant phyla, and instead most strongly affected phyla in lower abundance (e.g., Cyanobacteria, Proteobacteria, and Tenericutes) (adapted from Sylvia et al., 2016).