Probiotics Supplementation Alleviates Endotoxemia-induced Behavioral Deficits in Mice

Abstract

Objective: The gut microbiota plays a critical role in maintaining normal mental health. Studies have highlighted
the role of probiotics in monitoring the bacterial population and modulating the gut-brain axis. Probiotic
supplementation has received considerable attention as a potential therapeutic regime for the treatment of
behavioral abnormalities. The present study elucidated the modulatory role of probiotics alone or as adjuncts with
an agonist of the antipsychotic peptide neurotensin (NTS1) on behavioral deficits induced by endotoxin, bacterial
lipopolysaccharide (LPS). Materials and Methods: Five groups of mice were maintained: control, LPS, LPS
+ probiotics (Pro), LPS + NTS agonist (PD), and LPS + pro + PD. Mice were challenged with LPS (1 mg/kg
bw) for 5 days, followed by supplementation of probiotics (0.6 g/kg bw), PD (50 μg/kg bw), and a combination
of pro and PD for 4 weeks. Results: LPS-exposed mice showed sickness behavior (decrease in food and water
intake), anxiety behavior (reduction in time duration, entries in the central square in the open-filed arena, and
entries in the open arm in the elevated plus maze), and depressive behavior (increment in immobility time in
the force swimming test). A significant reduction in sickness, anxiety, and depressive behaviors as compared to
their LPS counterparts on supplementation of probiotics alone or in combination withNTS1 agonist; the efficacy
was enhanced in the latter. Probiotics supplementation alone or in combination with NTS1 agonist, reduced the
plasma levels of tumor necrosis factor-α, interleukin-6 (IL-6), and corticosterone, and increased plasma levels of
IL-10 might be due to increased beneficial bacteria Bifidobacteria and a decreased population of harmful bacteria
Clostridia. Conclusion: Probiotic supplementation has the potential to prevent behavioral abnormalities, restore
the homeostasis of the microbiota, and may be used as a therapeutics adjunct along with other anti-psychotic drugs
for mental illness.