Obesity is currently at pandemic proportions and not only impairs metabolic homeostasis, but is also a risk factor for psychological disorders including depression. Although the underlying mechanisms of these associations are largely unknown, alterations in the communication between the gastrointestinal tract and the nervous system (also called the gut-brain axis) could play a key role.

A new study, led by our group, the Microbial Ecology, Nutrition and Health Research Unit at the Institute of Agrochemistry and Food Technology-Spanish National Research Council (IATA-CSIC) in Valencia (Spain), has found that the probiotic Bifidobacterium pseudocatenulatum CECT 7765 restores some of the neurochemical and behavioral changes found in diet-induced obese mice.

The study’s main objective was to explore the role of B. pseudocatenulatum CECT 7765 —a strain selected on the basis of its anti-inflammatory properties demonstrated in a previous pre-clinical study by our research group—in reversing the adverse endocrine and neurobehavioral consequences of obesity by modulating the gut-brain axis. We fed adult male mice either a standard diet or high-fat diet, supplemented with either the probiotic strain (a daily dose of 1 x 109 colony forming units) or a placebo (10% skimmed milk) for 13 weeks.

Behavioral tests (sucrose and saccharin preference test, light-dark box test, open field test, forced swimming test, acute immobilization stress and acute social stress) were performed as sensitive indicators of anxious and depressive-like behavior, and immune and neuroendocrine parameters were also analyzed. As previously reported, HFD-induced obesity led to body weight gain, increased fat mass and metabolic alterations. B. pseudocatenulatum CECT 7765 ameliorated body weight gain, increased white adipose tissue and the metabolic alterations found in obese mice.

HFD-induced obesity was related to several neurochemical and behavioral alterations that were indicative of an altered stress response and a depressive-like phenotype. Noticeably, the obesity-increased responsiveness to acute physical and social stress in obese mice—assessed before and after stress exposure via corticosterone levels in stools—was ameliorated by B. pseudocatenulatum CECT 7765. This bifidobacterial strain also attenuated the obesity-induced anhedonia (characteristic of depression) in the sucrose preference test, parallel to reductions in serum leptin in obese mice. We also detected a significant reduction of leptin receptor (OB-R) expression in the hippocampus of obese mice, whereas the administration of B. pseudocatenulatum CECT 7765 tended to increase the leptin receptor expression (OB-R) in the intestine and hippocampus, suggesting an improvement of leptin signaling whose impairment has been related to obesity-associated depression. The probiotic did not have a significant effect on the relative gene expression of glucocorticoid receptors in the hippocampus, although it attenuated the exaggerated stress response characteristic of obese mice.

Finally, we studied changes in catecholamines due to their possible role in mood and behavioral disorders. B. pseudocatenulatum restored the obesity-induced reductions in adrenaline in the hypothalamus, which plays a role in centrally controlling energy balance. Furthermore, B. pseudocatenulatum also ameliorated the alterations of serotonin levels in the hippocampus, which might be involved in the attenuated obesity-associated depressive-like behavior we observed.

Regarding immune parameters, B. pseudocatenulatum CECT 7765 reduced the obesity-induced upregulation of TLR2 gene expression in the hippocampus and its protein levels in the small intestine. TLR2 signaling is part of some innate immune responses and these results suggest that the probiotic could act beyond the gut through its anti-inflammatory effects, which theoretically could contribute to the restoration of the serotonin levels in the hippocampus.

In conclusion, these pre-clinical results show that B. pseudocatenulatum CECT 7765 might play a role in depressive-like behavior comorbid with obesity through immunomodulatory mechanisms and changes in endocrine factors and neurotransmitters. Further follow-up studies in humans will have to confirm the role of specific probiotics in improving depression associated with obesity.

 

Reference:

Agusti A, Moya-Pérez A, Campillo I, et al. Bifidobacterium pseudocatenulatum CECT 7765 ameliorates neuroendocrine alterations associated with an exaggerated stress response and anhedonia in obese mice. Mol Neurobiol. 2018; 55(6):5337-52. doi: 10.1007/s12035-017-0768-z.

Yolanda Sanz
Yolanda Sanz
Yolanda Sanz holds a PhD in Pharmacy and is Professor of the National Research Council (CSIC) at the Institute of Agrochemistry and Food Technology (IATA) in Valencia, Spain. She is principal investigator of the Research Unit on Microbial Ecology, Nutrition and Health at IATA-CSIC. Her scientific field of interest is the role of the human microbiota in health and diseases, which affect the immune and neuroendocrine systems. Currently, she coordinates one of the largest EU projects on the human microbiome that integrates 30 partners of the EU and of USA, CA, NZ and AU (MyNewGut; www.mynewgut.eu). Her scientific contributions are reflected in more than 150 articles published in international peer-reviewed journals, 170 participations in conferences and eight patents.