Combined effects of calorie restriction and chronic stress on systemic inflammation and gut microbiota in rats exposed to Leptospira interrogans lipopolysaccharide.

BACKGROUND

Calorie restriction (CR) is widely studied for its anti-inflammatory and immunomodulatory effects. However, under conditions of chronic stress-such as those experienced during war, displacement, or famine-its impact on immune function remains poorly understood. In such contexts, combined nutritional and psychosocial stress may exacerbate inflammation and compromise host defences against pathogens.

OBJECTIVE

To investigate how the combination of moderate calorie restriction and chronic social stress affects systemic immune responses and gut microbiota composition following exposure to Leptospira interrogans lipopolysaccharide (LPS) in rats.

METHODS

Male Wistar rats were assigned to either ad libitum feeding (control) (n = 6), calorie restriction (CR, 30 % reduction) (n = 12), or CR combined with chronic overcrowding stress for 14 days (n = 12). All animals were subsequently challenged with Leptospira LPS. Immune gene expression was analyzed in peripheral blood using RT-qPCR arrays. Culture-based quantification of fecal microbiota was performed to assess compositional changes. Correlations between microbiota and cytokine gene expression were evaluated.

RESULTS

Compared with the control group, CR increased Il10 expression and increased the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, suggesting an anti-inflammatory and microbiota-supportive effect. In contrast, relative to the CR-only group, rats exposed to CR combined with chronic social stress showed marked upregulation of pro-inflammatory cytokine genes (Il1b, Il6, Tnf) and a shift toward gut dysbiosis, characterized by increased abundance of Klebsiella spp., Escherichia coli, and Enterococcus species.

CONCLUSION

A combination of chronic stress and calorie restriction can promote inflammation and cause gut dysbiosis, which may lead to a more severe form of leptospirosis.