Fermented Cabbage Brine as a Functional Dietary Modulator of Neuroinflammation, Oxidative Stress, and Anxiety-Like Behavior in Lipopolysaccharide-Challenged Mice

Abstract

Fermented foods are increasingly recognized for their health-promoting properties, but little is known about the effects of sauerkraut brine (SB), a by-product of cabbage fermentation, on systemic inflammation and neuro-inflammatory responses. This study aimed to investigate the immunomodulatory, antioxidant, and behavioral effects of SB oral treatment in a mouse model of low-dose lipopolysaccharide (LPS) challenge. The SB was prepared by traditional spontaneous cabbage fermentation and analyzed for pH, microbiological profile, and acidity. At the end of fermentation, the brine contained a high level of viable lactic acid bacteria (LAB) (1.8 × 10⁶ CFU/ml). Mice were pretreated orally with SB, heat-treated SB (htSB), or saline for 4 weeks before single or repeated LPS injection (0.5 mg/kg). Safety assessments, including body weight, food intake, and locomotor activity, did not indicate adverse effects with either form of SB. In the acute LPS model, SB pretreatment significantly reduced mRNA expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the prefrontal cortex compared to the saline-pretreated group. Interestingly, the expression of IL-10, strongly induced by LPS, was also significantly reduced by SB, suggesting modulation of both pro- and anti-inflammatory signaling pathways. These protective effects were less pronounced in the heat-treated SB group, suggesting that viable bacteria or heat-sensitive components may be critical for bioactivity. In the repeated LPS model, SB prevented LPS-induced depletion of glutathione (GSH) and preserved total antioxidant capacity (TAC), while heat-treated SB provided no protection and resulted in increased protein carbonylation and decreased TAC. No significant changes in the activities of antioxidant enzymes (SOD1/2, CAT, GR, GSH-Px, GST) were observed. Behavioral tests using the open-field paradigm showed that all groups exhibited prolonged sickness behavior after repeated LPS exposure, despite a two-day washout period. However, only the SB group showed delayed recovery, with reduced horizontal and vertical activity lasting 1 day longer than in the other groups. Nevertheless, pretreatment with SB and heat-treated SB prevented the LPS-induced reduction in time spent in the central zone, a commonly used measure of anxiety-like behavior, suggesting a possible anxiolytic effect. In conclusion, SB exhibits anti-inflammatory and antioxidant properties associated with systemic LPS-induced neuroinflammation and may reduce anxiety-like behavior. These effects appear to be dependent on heat-sensitive constituents or microbial viability. The findings support further investigation of SB as a functional dietary intervention targeting neuro-immune health.