Written by Joyce Smith, BS. Students, who drank milk containing the probiotic Lactobacillus casei [called Shirota (LcS)] 8 weeks prior to taking an important exam, experienced significantly lower salivary cortisol levels while taking the exam. Their rate of cold and flu symptoms were also significantly lower during the 8 weeks prior to the exams when compared to control.

shutterstock_295871813Studies on probiotic bacteria are telling us that a bidirectional communication or interaction between intestinal bacteria and the central nervous system exists and that exposure to stress intensifies this communication. 1 When the brain senses psychological stress, it can modulate (alter or change ) the intestinal microbiota composition and the gut functions by sending signals via the sympathetic and parasympathetic nervous systems and the hypothalamus –pituitary-adrenal (HPA) axis. 2 Conversely, our intestinal microbiota can affect our susceptibility to stress and stress-induced symptoms through a system of signaling that involves the neural, endocrine and immune systems 3,4

The objective of this study is to examine the potential role played by a particular strain of Lactobacillus casei [called Shirota (LcS)] in reducing stress and the gut–brain neural pathways involved.

Researchers conducted three double-blind, placebo-controlled trials to examine if LcS can modify the psychological and physical stress experienced by healthy Japanese fourth-grade medical students preparing for a national examination required for academic promotion.

149 students from 3 trials conducted in 2012, 13, and 2014 were randomly selected to receive either LcS or placebo milk for 8 weeks prior to their national exam. 140 students completed the trials and were included in the analyses. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed.

Results:

Effect of LcS on psychological stress:

  • In all 3 trials, STAI state anxiety scores peaked the day before exams and were significantly higher compared with baseline scores for both LcS and placebo groups. (placebo: 37.4 ± 1.1 and 48.7 ± 1.4, < 0.01, LcS: 38.7 ± 0.8 and 50.7 ± 1.2, < 0.01)

Effects of LcS on Salivary Cortisol levels:

  • In all 3 trials, salivary cortisol levels tended to increase as the exam day approached. Independently, the 3 trials showed an increase in salivary cortisol levels in the LcS group that were not statistically significant. However, when data from all three trials were pooled, the cortisol change from baseline was significantly lower in the LcS group compared to the placebo group on the day before the exam (LcS vs placebo, < 0.05)

Effect of LcS on physical symptoms:

  • Two weeks prior to the exam date, the rate of symptoms increased in the placebo group. However, symptoms decreased in the LcS group over the 8-week period prior to exams.
  • The rate of cold and flu symptoms (during weeks 5-6) and abdominal symptoms (during weeks 7-8) were significantly lower than in the placebo group. (P<0.05)

Researchers also conducted an animal study. Rats were given feed with and without LcS for 2 weeks, then subjected to water avoidance stress (WAS). Immediately following WAS, plasma corticosterone concentration and the expression of stress-associated protein cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured. In an electrophysiological study, urethane-anesthetized rats were given intragastric LCS, then monitored for gastric vagal afferent nerve activity (GVA) using 3 different concentrations of LcS on test rats and saline on the control.

Results:

  • Rats exposed to WAS for one hour had significantly increased plasma corticosterone levels compared to naïve rats. P<0.01
  • In rats pretreated with LcS for 2 weeks, increased plasma corticosterone levels were significantly reduced compared to control rats.
  • (WAS-control: 172.3±20.5 ng/mL, WAS-LcS: 94.1±20.7 ng/mL, p < 0.05)
  • LcS treatment also reduced the number of cells in the hypothalamus of the brain that are responsible for corticosterone levels; however, the differences in cell counts between the LcS treated rats and the controls did not reach statistical significance.

Effect of LcS on gut-to-brain signaling pathway:

  • Intragastric administration of LcS stimulated GVA activity in a dose-dependent manner. Peak values of GVA activity were reached at LcS concentrations of CFU 109 and 1010 (p < 0.01 and p < 0.05), respectively (Williams’ test). Intragastric administration of saline had no effect on GVA.

Conclusion:

In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly reduced, while the number of cells involved with cFos and corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) of the brain were also reduced. In addition, LcS stimulated gastric vagal afferent activity in a dose-dependent manner.

Based on these results the authors suggest that when the body is subjected to stressful conditions, LcS may communicate via the gastro-vagal-afferent nerve pathway and signal the brain to be less reactive to stress.

Limitations of the study:

Studies comparing the effects of LcS to other probiotic strains must be conducted. Also, the fermented milk containing LcS may have contained other fermented products in addition to lactic acid that could have affected the results.

Source: Takada M., Nishida K., Kataoka-Kato A. et al. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut–brain interaction in human and animal models. Neurogastroenterol Motil (2016) 28, 1027–1036 doi: 10.1111/nmo.12804

© 2016 John Wiley & Sons Ltd

Posted August 15, 2016.

References:

  1. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology. 2012;10(11):735-742.
  2. Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology. 2009;136(6):2003-2014.
  3. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. The Journal of physiology. 2004;558(1):263-275.
  4. Tillisch K. The effects of gut microbiota on CNS function in humans. Gut microbes. 2014;5(3):404-410.