The microbiota-gut-brain axis: neurobehavioral correlates, health and sociality

Abstract

Recent data suggest that the human body is not such a neatly self-sufficient island after all. It is more like a super-complex ecosystem containing trillions of bacteria and other microorganisms that inhabit all our surfaces; skin, mouth, sexual organs, and specially intestines. It has recently become evident that such microbiota, specifically within the gut, can greatly influence many physiological parameters, including cognitive functions, such as learning, memory and decision making processes. Human microbiota is a diverse and dynamic ecosystem, which has evolved in a mutualistic relationship with its host. Ontogenetically, it is vertically inoculated from the mother during birth, established during the first year of life and during lifespan, horizontally transferred among relatives, mates or close community members. This micro-ecosystem serves the host by protecting it against pathogens, metabolizing complex lipids and polysaccharides that otherwise would be inaccessible nutrients, neutralizing drugs and carcinogens, modulating intestinal motility, and making visceral perception possible. It is now evident that the bidirectional signaling between the gastrointestinal tract and the brain, mainly through the vagus nerve, the so called "microbiota-gut-vagus-brain axis," is vital for maintaining homeostasis and it may be also involved in the etiology of several metabolic and mental dysfunctions/disorders. Here we review evidence on the ability of the gut microbiota to communicate with the brain and thus modulate behavior, and also elaborate on the ethological and cultural strategies of human and non-human primates to select, transfer and eliminate microorganisms for selecting the commensal profile.

Keywords: evolutionary psychology; kissing; microbiota–gut–brain axis; neurobiology; psychoneuroimmunology; social bonds.

FIGURE 1

(A) Microbiota–gut–brain (MGB) axis. Direct and indirect pathways support the bidirectional interactions between the gut microbiota and the central nervous system (CNS); involving endocrine, immune and neural pathways. On the afferent arm (blue arrows): (1) lymphocytes may sense the gut lumen and internally release cytokines which can have endocrine or paracrine actions, (2) Sensory neuronal terminals, such as on the vagus nerve may be activated by gut peptides released by enteroendocrine cells, (3) Neurotransmitters or its precursors produced as microbiota metabolites may reach the gut epithelium having endocrine or paracrine effects. (4) Centrally, after brainstem relays (e.g., nucleus tractus solitarii) a discrete neural network has been described consistently involving the amygdala (Am) and the insular cortex (IC) as main integrators of visceral inputs. Consistently hypothalamic (Hy) activation initiates the efferent arm (red arrows): (5) corticosteroids, release as results of the hypothalamic–pituitary–adrenal (HPA) axis activation, modulates gut microbiota composition. (6) Neuronal efferent activation may include the so called “anti-inflamatory cholinergic reflex” and/or sympathetic activation, both liberating classical neurotransmitters that may affect directly the gut microbiota composition. (B) Health conditions affected by the MGB axis. Recent and growing evidence suggests that several health conditions may be affected by intestinal microbiota, including: visceral pain (McKernan et al., 2010; Wang et al., 2010; Clarke et al., 2012), autism spectrum disorders (Adams et al., 2011; de Theije et al., 2011; Thomas et al., 2012; Wang et al., 2012), obesity (Turnbaugh and Gordon, 2009; Davey et al., 2012; Manco, 2012), cardiovascular risk (Tang et al., 2013), anxiety/depression (Bravo et al., 2011; Heijtz et al., 2011; Foster and McVey Neufeld, 2013), and multiple sclerosis (Berer et al., 2011; Lee et al., 2011).

FIGURE 2

The typical structure of the multi-layered Hamadryas baboon society. The smaller social unit (a “one-male-unit”, OMU) in the Hamadryas society is that formed by an adult male (triangles), adult females (circles) and their offspring. In these units social relationships tend to be circumscribed to members of the same unit (expressed here by arrows, representing social relationships -within bold circles). These units are often formed when larger OMUs fission or when young bachelors sequester peripheral (usually young) females from a large OMU; retaining them in close proximity by force and aggression. Adult females in the same OMU are seldom kin. This produces that strong social relationships (bold arrows) are usually established between a female and her unit’s male, not among females in the same OMU. While both sexes can have relatives in other OMUs, social contacts among females from different units are less common (dotted arrows), whereas adult males may in fact establish strong alliances with males from other units (which may actually be their kin) forming “clans” (bold arrows across different OMUs). Spatial association between individuals of different OMUs (e.g., foraging in relative proximity) can result in the third level of the Hamadryas society: a “band” (medium-sized dotted ovals). Finally, different bands congregate in the same cliffs to sleep, forming the largest identifiable group: the “troop” (largest dotted oval).

FIGURE 3

Behaviors supporting an association between microbial-transmission and social bonding in primates. The intense sociality of primates provides several different direct (i.e., with contact between individuals) and indirect (i.e., mediated by any environmental feature) opportunities for the transmission of microbial-life associated to a social-bonding mechanism. Important examples (described in more detail in main text) include: (upper-left) mouth-to-mouth contact (in chimpanzees, Pan troglodytes): where microbial-life may be directly transmitted in saliva between individuals; (upper-right) social grooming (in savannah baboons, Papio cynocephalus): where groomers may feed on ectoparasites or food-debris, allowing for the transmission of microbiota; (bottom-right) lactation (in vervet monkeys, Chlorocebus aethiops): where microbiota directly acquired from the mother helps feeding bacterial communities which in turn help offspring assimilating milk’s nutrients; and (bottom-left), indirect transmission of microbiota mediated by a social tradition (i.e., touching religious objects), a possible pathway for the homogenization of microbial-life across individuals of a culturally defined human group (all photos by Augusto J. Montiel-Castro).