Abstract
Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity) and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS) shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuates increases in some (inflammasome dependent, IL-1 and IL-18), but not all (inflammasome independent, IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.
Highlights
The enteric mucosal immune system is a unique immunological site that must maintain a balance between responding to harmful pathogens and avoiding inappropriate immune responses to food or symbiotic bacteria
Antibiotic administration effectively reduced commensal bacterial load The number of colony forming units measured in the fecal samples of rats receiving antibiotics was significantly lower than control rats (p,0.001) (Figure 3A)
This decrease in colony forming units (CFU) count suggests that antibiotic administration significantly reduced the commensal bacteria, as expected
Summary
The enteric mucosal immune system is a unique immunological site that must maintain a balance between responding to harmful pathogens and avoiding inappropriate immune responses to food or symbiotic bacteria. Several diverse factors may impact the mucosal barrier or the composition of the commensal bacteria including antibiotic use [7,8], changes to diet or hygiene [7,8], and activation of the stress response [9,10,11,12,13,14]. Stress-induced changes to the intestinal barrier or the composition of the commensal bacteria appear to drive some aspects of stress-evoked mucosal and even systemic immune activity. Stress-induced disruptions to the mucosal barrier, for example, are linked to increased serum cytokine levels including tumor necrosis factor a (TNFa) [20]. Reducing the commensal bacteria via antibiotic administration attenuates chronic or repeated stress-induced enhancements in splenic macrophage activity [18] and circulating levels of the cytokine interleukin-6 (IL-6) [1]
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