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

TITLE=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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00269

DOI=10.3389/fcimb.2019.00269

ISSN=2235-2988

ABSTRACT=<p>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 <italic>Lactobacillus casei</italic> ATG-F1 (F1), <italic>L. reuteri</italic> ATG-F3 (F3), and <italic>L. reuteri</italic> 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 <italic>in vitro</italic> 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 <italic>Lactobacillus</italic>-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 <italic>Bacteroidales</italic> S24-7 and <italic>Prevotellaceae</italic> 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 <italic>Lactobacillus</italic>-treated mice, and the F4-treated group showed the highest fold changes in circadian rhythm-related genes (<italic>Dbp, Per1, Per2</italic>, and <italic>Per3</italic>). Conclusively, <italic>L. reuteri</italic> 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.</p>