Acute and repeated exposure to social stress reduces gut microbiota diversity in Syrian hamsters.

Mood and anxiety disorders are strongly associated with somatic symptoms such as gastrointestinal distress (Bekhuis et al., 2014, Felice et al., 2015), and a high co-morbidity exists between stress-related neuropsychiatric symptoms and gastrointestinal disorders such as irritable bowel syndrome (Kanuri et al., 2016, Kennedy et al., 2012, Qin et al., 2014). One possibility is that stress impacts brain function and mental health via its effect on the gastrointestinal tract (for review see Dinan & Cryan, 2012, Dinan et al., 2015, Parashar & Udayabanu, 2016). Given that the available treatment strategies for a variety of stress-related neuropsychiatric disorders are inadequate for many, expanding our knowledge of a broader range of potential etiologic factors might lead to novel, more effective therapeutics (Culpepper et al., 2015, Haddad et al., 2015, Nestler et al., 2002). The mammalian gastrointestinal tract houses over 100 trillion microorganisms (Eckburg et al., 2005), which are critical for vital functions such as processing and digestion of food, synthesis of vitamins, inhibition of pathogens, and immune system development and maturation (Ramakrishna, 2013). Thus, a stable and symbiotic relationship exists between these microorganisms, referred to as gut microbiota, and the host gastrointestinal system (Mayer et al., 2015). These microbiota are essential to homeostasis, and abrupt dysbiosis or absence of this vibrant community can compromise the physical and mental health of the host (Chang et al., 2008, Cryan, 2016, Luczynski et al., 2016, Turnbaugh et al., 2006). Recently, it has been demonstrated that there is bi-directional communication, referred to as the gut-brain axis, between the central nervous system and the gastrointestinal tract, and altering the gut microbiota during early development or adulthood changes both stress-related behavior and responsivity of the stress axis (Desbonnet et al., 2014, Diaz et al., 2011, Collins et al., 2013, Sudo et al., 2004). Many neuropsychiatric disorders and symptoms that are associated with gastrointestinal dysfunction are also caused or exacerbated by exposure to stress (Agid et al., 2000, Kessler, 1997, Saveanu & Nemeroff, 2012), and stress has been associated with significant alterations in the gut microbial community in mammals, including humans (Lyte et al., 2011). These stress-induced alterations are associated with consequences ranging from inflammation to increased anxiety-like behavior (Bailey & Coe, 1999, Bailey et al., 2011). Exposure to social stress, in particular, can cause or exacerbate disabling neuropsychiatric disorders, including depression and PTSD (Bjorkqvist et al., 2001, Qiao et al., 2016). Relatively little is known, however, about the direct impact of social stress on the gut microbial community and how these microbes, in turn, may affect behavior. Bailey et al. (2011) demonstrated that group-housed mice exposed to 6, 2 hr bouts of social disruption stress exhibited alterations of the gut microbial community characterized by a reduction in microbial diversity and richness. A similar response was observed in mice that were exposed to a more severe, 10-day social defeat procedure (Bharwani et al., 2016). There is even some evidence that a single, 2 hr exposure to a social defeat stressor in mice impacts gut microbiota (Galley et al., 2014), suggesting that even acute social stress might have effects on the gut. The current study utilizes a well-characterized resident-intruder model in Syrian hamsters (Jasnow et al., 2001, Potegal et al., 1993) to investigate whether exposure to social stress affects the commensal gut microbiota and, in particular, whether it does so differently in individuals that “win” a social conflict (i.e., become dominant) versus those that “lose” (i.e., become subordinate). Syrian hamsters are ideal candidates for the study of social stress because when weight- and age-matched conspecifics are paired, they readily produce aggressive and territorial behavior that rapidly results in the formation of a stable dominance relationship (Albers et al., 2002). This allows a direct comparison of commensal bacteria in dominants and subordinates. This comparison is not possible in mice because conspecifics generally do not fight; defeated mice are produced using a larger, more aggressive heterospecific (e.g., C57J/BL6 defeated by a CD-I mouse). An additional benefit of using hamsters is that their agonistic behavior during brief encounters is highly ritualized and rarely results in any tissue damage, allowing us to focus on the psychological, as opposed to physical, aspects of social stress (Huhman & Jasnow, 2005). Furthermore, no studies have examined whether the baseline composition of the gut microbiota alters behavioral responses to social stress. Thus, we also measured whether the baseline gut microbiota composition can predict whether an animal becomes dominant or subordinate after a subsequent agonistic encounter.