Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress

Abstract

Introduction: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. Methods and Results: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. Conclusions: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.