Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri Probiotics Modulate Inflammation, Attenuating Chronic Stress-Induced Liver Injury and Behavior in Rats.

BACKGROUND

Chronic stress disrupts systemic homeostasis and contributes to metabolic, psychiatric, and inflammatory disorders, often involving alterations in gut microbiota. Probiotics such as Lacticaseibacillus rhamnosus (L. rhamnosus) and Limosilactobacillus reuteri (L. reuteri) possess anti-inflammatory properties, but their combined effects on liver health and cognitive function remain underexplored.

OBJECTIVES

The aim of this study was to investigate whether supplementation with L. rhamnosus and L. reuteri mitigates inflammation, liver damage, and behavioral changes induced by chronic stress.

METHODS

Forty-seven male Wistar rats were assigned to 4 groups: control (C, n = 12), stress (S, n = 12), control probiotic (CP, n = 11), and stress probiotic (SP, n = 12). All animals received standard laboratory chow. A combined dose of L. rhamnosus and L. reuteri (1 × 109 colony-forming units/strain/d) was administered by gavage for 8 wk. Groups S and SP were subjected to a chronic mild unpredictable stress protocol during weeks 3-5, including stressors such as food/water deprivation, restraint, and light/dark cycle inversion. Behavioral, biochemical, inflammatory, hepatic, metabolic, and physiological parameters were assessed.

RESULTS

Probiotic supplementation significantly restored body weight gain (SP: 123.5 ± 17.5% compared with S: 98.2 ± 12.2%) and sucrose preference (SP: 19.96 ± 0.31% compared with S: 14.48 ± 4.16%). SP rats showed reduced concentrations of corticosterone (SP: 65.2 ± 31.2 ng/mL; S: 188 ± 112.6 ng/mL), noradrenaline (SP: 243 ± 163.6 pg/mL; S: 887.6 ± 476 pg/mL), and dopamine (SP: 318.6 ± 169 pg/mL; S: 582.8 ± 271 pg/mL). Supplementation also decreased alanine aminotransferase levels (SP: 131.6 ± 9.4 U/L compared with S: 147.6 ± 7.5 U/L) and hepatocyte nuclear area (SP: 11.35 ± 1.5 μm2 compared with S: 12.63 ± 1.7 μm2). In analyses of circulating cytokines, probiotics modulated inflammation by reducing IL-1β (SP: 115 ± 43 pg/mg; S: 343 ± 64 pg/mg) and IL-17 (SP: 356.5 ± 93 pg/mg; S: 674 ± 48 pg/mg), whereas IL-10 levels were increased (SP: 196.5 ± 11 pg/mg; S: 65 ± 28.6 pg/mg) (all P < 0.05).

CONCLUSIONS

L. rhamnosus and L. reuteri supplementation attenuated the metabolic, hormonal, inflammatory, and behavioral effects of chronic stress and preserved liver integrity in rats.