Promising Antidepressant Potential: The Role of Lactobacillus rhamnosus GG in Mental Health and Stress Response

Abstract

Chronic stress is linked to changes in brain physiology and functioning, affects the central nervous system (CNS), and causes psychiatric diseases such as depression and anxiety. In this study, antidepressant effects of the probiotic bacterium Lactobacillus rhamnosus GG (ATCC 53103) (LGG) (15 × 10⁸ cfu/ml/day) on the mechanisms playing a role in the pathophysiology of depression were investigated, and the results were compared with the effects of bupropion (20 mg/kg/day) and venlafaxine (20 mg/kg/day). A total of 56 male Wistar Albino rats were used in control, stress, bupropion, venlafaxine, LGG, bupropion + stress, venlafaxine + stress, LGG + stress groups, n = 7 each. Changes in the body weight of the rats during the experiment were determined by weight measurement. Gene expression levels were determined by the RT-PCR method. Four different behavioral tests were performed to evaluate depressive behaviors (sucrose preference test, three-chamber sociability test (social interaction test), elevated plus maze test, forced swim test). LGG treatment was effective in reducing depressive-like behaviors, increased BDNF level, 5-HT1A, DRD1, ADRA-2A, GABA-A α1, CNR1 expression levels in the hippocampus and NOD1 receptor expression level in the small intestine (p < 0.05), and also decreased neurodegeneration level, glial cell activity, and intestinal permeability in depressed rats. As a result, it was revealed in this study for the first time that the LGG probiotic bacterium has antidepressant properties and was found to be more effective than the antidepressant drugs bupropion and venlafaxine. Our results suggest that LGG is a potential psychobiotic bacterium and can be useful to treat depression. It may be an effective and useful option in combating depression.

Fig. 1

Schematic representation of the experimental design and antidepressant effects of LGG in the depressed rats

Fig. 2

1) Sucrose preference test (SPT): A) Rats that prefer sucrose water B) Rats that prefer both sucrose water and tap water, 2) A) Three-chamber sociability test; B) Rearing C) Social interaction with one stranger partner D) Social interaction with second stranger partner, 3) Elevated plus maze test 4) Forced swim test (FST)

Fig. 3

A Change in body weight (g) on the 14th, 35th and 56th days. B Total body weight gain (g) of the experimental groups during the experiment C) Decrease rate in body weight gain between 14-35th and 35-56th days

Fig. 4

A Sucrose preference test: (a) Percentage of sucrose consumption rate (%) and (b) weekly change in sucrose consumption (%), (F:2,21; p>0,05) B) Elevated plus maze test: Time spent in open arms (F:3,37; **p<0,01) C) Forced swim test (FST): Immobility time (F:10,67; ***p<0,001) D) Three-chamber sociability test (social interaction test): (a) time spent in center (F:2,48; *p<0,05), (b) time spent in right and left chambers (F:2,48; *p<0,05), (c) interaction time with stranger partners (F:1,14; p>0,05), (d) rearing numbers (F:3,17; **p<0,01)

Fig. 5

BDNF level (F:2,65; *p<0,05) and DRD1 (F:13,12; ***p<0,001), CNR1 (F:12,21; ***p<0,001), ADRA-2A (F:12,11; ***p<0,001), 5-HT1A (F:8,55; ***p<0,001), GABA-Α α1 (F:11,58; ***p<0,001), MC4R (F:15,59; ***p<0,001), NR3C2 (F:6,75; ***p<0,001), NLRP3 (F:1,88; p>0,05) in hippocampus tissue and NOD1 receptor expression levels in small intestine tissue

Fig. 6

Histological evaluation of the cortex tissue: red neurons and neuronal satellitosis. Control group (A), stress group (B), bupropion group (C), bupropion + stress group (D), venlafaxine group (E), venlafaxine + stress group (F), LGG group (G), LGG + stress group (H), (bar: 50.0μm, 20X, HE). Black arrows show normal neurons, red arrows show damaged neurons, and green arrows show increased number of neuroglial cells (neuronal satellitosis)

Fig. 7

Histological evaluation of the small intestine tissue: intestinal permeability. Control group (A), stress group (B), bupropion + stress group (C), venlafaxine + stress group (D), LGG + stress group (E), (bar: 100.0μm, 20X, HE). S: Submucosa, ▲ : Muscularis layer, ⬆: Villus layer, ⋆ : Ulceration area

Fig. 8

1. Caspase-3 activity in the cortex tissue, 2. Ki-67 activity in the cortex tissue, (bar: 50.0μm, 40X), 3. Graphical representation of histopathology results, control group (A), stress group (B), bupropion group (C), bupropion + stress group (D), venlafaxine group (E), venlafaxine + stress group (F), LGG group (G), LGG + stress group (H)