Multidisciplinary and Comparative Investigations of Potential Psychobiotic Effects of Lactobacillus Strains Isolated From Newborns and Their Impact on Gut Microbiota and Ileal Transcriptome in a Healthy Murine Model.

Bo Ram Beck,Do Yeun Jeong,Gun-Seok Park,Won Ho Song,Yong Hyun Lee,Jihee Kang,Sunghoon Im

doi:10.3389/fcimb.2019.00269

Bo Ram Beck, Do Yeun Jeong + Show 5 more

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https://doi.org/10.3389/fcimb.2019.00269

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Abstract

Psychobiotics are probiotic microorganisms that may exert positive influence on the psychological status of the host. Studies have revealed immunological and microbiological correlations of gut microbiota and the gut-brain axis, and have investigated psychobiotics based on the findings of the gut-brain axis. Considering their mode of actions, the present study sets anti-inflammatory effect, neurotransmitter modulation, and gut microbiota modulation as three essential criteria to evaluate Lactobacillus casei ATG-F1 (F1), L. reuteri ATG-F3 (F3), and L. reuteri ATG-F4 (F4) isolated from newborns as psychobiotics candidates in a healthy mouse model and compares the results with a non-treated control group and an ampicillin-induced gut dysbiosis (Amp) group as a negative control. The F3 and F4 strains showed anti-inflammatory effects in vitro in RAW264.7 murine macrophages, and the level of anti-inflammatory cytokine interleukin (IL)-10 increased in ileums of mice orally administered with the F4 strain. Serum dopamine level significantly increased only in the F4-treated group as compared with the control group. Serum serotonin level was unaffected in Lactobacillus-treated groups, while a significant decrease in serum serotonin level was observed in the Amp group. Bacteroidetes population increased in fecal samples of the F4-treated group as compared with the control, and Bacteroidales S24-7 and Prevotellaceae population significantly increased at family level in fecal samples from the F4-treated group as compared with the control. In contrast, the Amp group showed an increase in the level of Proteobacteria and a decrease in the level of Bacteroidetes as compared with the control group. Transcriptome analysis revealed a distinctive clustering in ileums from the F4-treated group as compared to other experimental groups. In addition, the circadian rhythm pathway showed maximum enrichment in ileums of Lactobacillus-treated mice, and the F4-treated group showed the highest fold changes in circadian rhythm-related genes (Dbp, Per1, Per2, and Per3). Conclusively, L. reuteri ATG-F4 is suggested as a potential psychobiotics through demonstrations of anti-inflammatory effects, serum dopamine modulation, and gut microbiota modulation in a healthy murine model in the present study. Moreover, we carefully suggest gut circadian rhythm modulation as another important criterion of psychobiotics, which may have an important role in the gut-brain axis.

Highlights

Mens sana in corpore sano, a Latin phrase that means a healthy mind in a healthy body, implies that the physical and psychological systems are closely linked together
IL-10 concentration significantly increased in the ileums of the F4-administrated group as compared with ileums from the control group and the ampicillin-induced gut dysbiosis (Amp) group at the end of 4 weeks of Lactobacillus administration (Figure 1C)
These results suggest that the oral microbial supplementation or gut microbiota disruption may influence the levels of circulatory neurotransmitters of the host

Summary

INTRODUCTION

Mens sana in corpore sano, a Latin phrase that means a healthy mind in a healthy body, implies that the physical and psychological systems are closely linked together. Recent studies on the microbiota-gut-brain axis revealed the interaction, correlation, and association of the gut microbiota with the mental status of the host (Lyte and Cryan, 2014; Johnson and Foster, 2018). Based on the findings and hypotheses of previous studies on the gut-brain axis, we set three criteria of potential psychobiotic properties, including anti-inflammatory potentials, influence on neurotransmitters, and modulation of gut microbiota, to develop a procedure to evaluate psychobiotics. By focusing on these criteria, we isolated three Lactobacillus species from new born infants, namely, L. casei ATG-F1 (F1), L. retueri ATG-F3 (F3), and L. reuteri ATG-F4 (F4), and investigated their potential psychobiotic properties

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