“The probiotic strain, Lactobacillus casei strain Shirota can relieve many aspects of the stress response, especially gastrointestinal dysfunction,” said corresponding author Kouji Miyazaki, PhD, director of the Food Research Department of Yakult Central Institute, Tokyo, Japan.
In the study, beginning eight weeks prior to the examination, 23 medical students drank milk that had been fermented by L. casei strain Shirota, while 24 control students consumed non-fermented (placebo) milk that was otherwise identical in such parameters as taste, color, and nutrition. Neither group of students knew which milk they had received.
Weekly, the subjects answered a questionnaire concerning levels of five common abdominal symptoms, such as “abdominal discomfort and pain”. They also responded to a questionnaire on anxiety levels. Additionally, the investigators measured certain physiological parameters, such as salivary cortisol—a stress hormone.
Less stress for probiotics group
The study demonstrated that daily consumption of the probiotic milk reduced gastrointestinal pain and dysfunction, as well as the feeling of being stressed out. It also dampened the rise in salivary cortisol, said Miyazaki.
Additionally, the L. casei strain Shirota changed levels of expression of stress-related genes. In placebo group students, as the examination date approached, expression soared in 179 stress-related genes, while rising much less in the students who consumed the probiotics.
The percentage of bacteria from the stress-related Bacteroidetes species increased prior to exams only in the placebo group. Meanwhile, the students on the probiotics maintained healthier and more diverse populations of gut bacteria throughout the time leading up to the examination. The investigators suspect this contributed to reducing stress symptoms.
Stress response ‘controlled by probiotics’
The researchers used 16S rRNA gene amplicon sequence analysis to census the bacteria.
“These findings indicate that the stress responses are controlled by probiotics at a higher level of the stress system, through the brain-gut axis,” said Miyazaki.
”Thus, the probiotic strengthens the resilience of our stress response system.”
Miyazaki said the idea for the study had originated from indications that probiotics mitigated stress-related gut diseases such as irritable bowel syndrome.
Expert urges caution
Dr. Emeran Mayer, director, Oppenheimer Center for Neurobiology of Stress, David Geffen School of Medicine, UCLA, said the study adds much-needed human data to the field of gut microbiota brain interactions, and the effect of probiotics on these interactions.
“The authors have to be congratulated on a well-designed study which includes both behavioral and biological read outs, but I would not take it as definitive. One problem is that 13 of the co-authors were employees of Yakult, the sponsor of the study,” Mayer said.
“Another question is how generalizable some of the findings are, given the small sample size. This is particularly true for the behavioral readouts. Normally, when you do randomized controlled trials with probiotics you need hundreds of patients to demonstrate clinical effects. And since symptoms are more variable than biological markers, you need a large sample to show a significant effect on symptoms,” he added.
Some small changes
He noted that in the study there was no significant effect on anxiety and feelings of stress, and small changes in other factors like abdominal symptoms between the probiotic group and the placebo group. There were some changes in the composition of the microbiota, he said, but they were small changes in number and abundance of species.
“One thing that does look interesting is the gene expression profile: one day before there was this big difference between the probiotic group and the placebo group.”
Mayer did say that there is evidence from human studies that acute and chronic stress is associated with change in gene expression profiles of circulating immune cells. He added that there are preclinical studies showing clear effects of probiotics on gene expression in the brain, but there are no human studies looking at stress-induced gene expression profiles in peripheral immune cells that involve a probiotic intervention.
“It’s remarkable when you think about it that a probiotic intake might have such a profound effect on the immune system. Hopefully other people will come out with similar reports with larger sample sizes that confirm these intriguing findings,” Mayer concluded.
Opportunity for further studies
Dr. Jennifer Mulle, assistant professor, Department of Epidemiology, Emory University, said that the study advances the body of work showing that administration of probiotics can influence emotional state and response to stress.
She added that a strength of the study was that all individuals in the study had a common stressor applied in the same way at the same time.
“While this may limit the generalizability of these findings, their wise selection of study sample likely allowed the authors to see an effect in a relatively small sample size. This study should be replicated in additional populations. Future studies should also explore other types and strains of probiotics,” Mulle said.
One limitation Mulle noted was that the gene expression analysis was limited to males.
“Additional studies should investigate expression changes in females alongside males. While more work is required, this study adds to the tantalizing possibilities that have already been hinted at for the role of probiotics in human health,” she said.