Caffeine plays a prevention role in stress-induced depression by modulating gut-brain axis function

Background

Caffeine intake is inversely associated with depression in epidemiological studies and can impact gut microbiota. Considering the close relationship between depression and gut microbiota, we conducted this study to investigate whether prophylactic caffeine use could influence the development of depression by affecting gut-brain axis.

Methods

Male C57BL/6J mice were randomly divided into three groups: a control group, one group receiving chronic unpredictable stress (CUS) as CUS group, and one group receiving CUS after intraperitoneal injection with caffeine (CAF) as CAF group. Depressive- and anxiety-like behaviors were assessed, and gut-brain axis related molecules were examined.

Results

Compared to control group, CUS group had significantly lower body weight, sucrose preference, center distance (%) and higher immobility time; however, the values of these indexes were similar between control group and CAF group. Furthermore, the significantly decreased intestinal barrier integrity-related factors (Zonula Occludens-1 (ZO-1), claudin-1 and Mucin2 (MUC2)) in CUS were not observed in CAF group; and the altered levels of two inflammation factors in plasma (lipopolysaccharide (LPS) and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)) and four inflammation-related factors in hippocampus (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), adenylyl cyclase (AC) and brain-derived neurotrophic factor (BDNF)) in CUS group were not observed in CAF group. In addition, we found that six differential genera were identified between control group and CUS group, but not between control group and CAF group; and sucrose preference were significantly correlated with five of these six differential genera.

Conclusions

The results suggested that early caffeine intervention might prevent depression by regulating gut microbiota, intestinal barrier integrity and neuroinflammation.