Altered fecal microbiota composition in all male aggressor‐exposed rodent model simulating features of post‐traumatic stress disorder

Abstract

The bidirectional role of gut-brain axis that integrates the gut and central nervous system activities has recently been investigated. We studied "cage-within-cage resident-intruder" all-male model, where subject male mice (C57BL/6J) are exposed to aggressor mice (SJL albino), and gut microbiota-derived metabolites were identified in plasma after 10 days of exposure. We assessed 16S ribosomal RNA gene from fecal samples collected daily from these mice during the 10-day study. Alpha diversity using Chao indices indicated no change in diversity in aggressor-exposed samples. The abundance profile showed the top phyla were Firmicutes and Bacteroidetes, Tenericutes, Verrucomicrobia, Actinobacteria and Proteobacteria, respectively. The phyla Firmicutes and Bacteroidetes are vulnerable to PTSD-eliciting stress and the Firmicutes/Bacteroidetes ratio increases with stress. Principal coordinate analysis showed the control and aggressor-exposed samples cluster separately where samples from early time points (day 1-3) clustered together and were distinct from late time points (day 4-9). The genus-based analysis revealed all control time points clustered together and aggressor-exposed samples had multiple clusters. The decrease in proportion of Firmicutes after aggressor exposure persisted throughout the study. The proportion of Verrucomicrobia immediately decreased and was significantly shifted at most of the later time points. The genus Oscillospira, Lactobacillus, Akkermansia and Anaeroplasma are the top four genera that differed between control and stressor-exposed mice. The data showed immediate effect on microbiome composition during a 10 day time period of stress exposure. Studying the longitudinal effects of a stressor is an important step toward an improved mechanistic understanding of the microbiome dynamics.

Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome

“…Differential abundance analysis of individual taxa revealed multiple bacterial taxa that were increased or decreased in the sleep-disrupted group compared to controls, including an increase in the Firmicutes:Bacteroidetes (F:B) ratio and a decrease in Lactobacillus, Actinobacteria, and Bifidobacterium, all of which have established physiological impacts. An increase in the F:B ratio is a blunt measure of community shift and has been seen in many pathological states including obesity [55,56], chronic stress [57], as well as an acute short sleep paradigm in humans [14] and a chronic sleep fragmentation paradigm in rodents [16]. The phylum Actinobacteria, genus Bifidobacterium, and genus Lactobacillus were all low in sleep-disrupted mice.…”

“…The ratio of the two most prevalent phyla in the mammalian gut, the Firmicutes:Bacteroidetes (F:B) ratio, is a blunt measure of community shift. An increase in the F:B ratio has been seen in obesity [55,56], stress [57], as well as models of acute [14] and chronic [16] sleep disruption. We found a significant sleep disruption-induced increase in the F:B ratio (Fig 4B) that was significant at R2 but not at R4.…”

It's what's on the inside that counts: stress physiology and the bacterial microbiome of a wild urban mammal

“…Since the HPA axis is deeply rooted in vertebrate phylogeny [57], similar rebalancing of digesta versus mucin glycan energy channels in response to stressors experienced by the host could be a conserved mechanism by which vertebrates regulate their microbiomes. Trade-offs between mucin glycan and digesta metabolizing bacteria are reported in laboratory mice exposed to chronic stressors [67][68][69], HIV patients experiencing mucosal barrier disruption [70], fasting vertebrates [71,72] and mammals undergoing torpor or hibernation [73][74][75][76][77]. Although these studies typically discuss the bacterial patterns observed within the context of diet or specific stressors, homologous HPA axis responses across these biological groups might provide an alternate or complimentary mechanism.…”

Targeting Gut Microbiome Interactions in Service-Related Gastrointestinal and Liver Diseases of Veterans

“…9 In animal models, PTSD is linked with differences in gut microbial composition, which can, in turn, modulate aggressive behavior and exert a negative influence on the mice that suffer because of this aggression. 10,11 Moreover, these changes can be transmitted by fecal transplant in rodent models, setting the stage for gut microbial modulation as an important avenue in PTSD. 10,11 Human studies are currently lacking in veterans with PTSD; however, patients with noncombat PTSD show altered gut microbial composition compared with those exposed to similar trauma but who did not develop PTSD.…”

“…10,11 Moreover, these changes can be transmitted by fecal transplant in rodent models, setting the stage for gut microbial modulation as an important avenue in PTSD. 10,11 Human studies are currently lacking in veterans with PTSD; however, patients with noncombat PTSD show altered gut microbial composition compared with those exposed to similar trauma but who did not develop PTSD. 12,13 The interaction between PTSD, depression and the onset of liver disease in veterans is a relevant question since several lifestyle-associated disorders can propagate liver disease.…”