Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress

Appl Environ Microbiol. 2016 May 31;82(12):3649-58. doi: 10.1128/AEM.04134-15. Print 2016 Jun 15.


Stress-induced abdominal dysfunction is an attractive target for probiotics. To investigate the effects of the probiotic Lactobacillus casei strain Shirota on abdominal dysfunction, a double-blind, placebo-controlled trial was conducted with healthy medical students undertaking an authorized nationwide examination for academic advancement. For 8 weeks, until the day before the examination, 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, respectively. In addition to assessments of abdominal symptoms, psychophysical state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and composition of the gut microbiota were analyzed using DNA microarray analysis and 16S rRNA gene amplicon sequence analysis, respectively, before and after the intervention. Stress-induced increases in a visual analog scale measuring feelings of stress, the total score of abdominal dysfunction, and the number of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examination was observed only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher numbers of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group. Our findings indicate that the daily consumption of probiotics, such as L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-associated responses of abdominal dysfunction in healthy subjects exposed to stressful situations.

Importance: A novel clinical trial was conducted with healthy medical students under examination stress conditions. It was demonstrated that the daily consumption of lactic acid bacteria provided health benefits to prevent the onset of stress-associated abdominal symptoms and a good change of gut microbiota in healthy medical students.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biota / drug effects*
  • Cluster Analysis
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Double-Blind Method
  • Female
  • Fermentation
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Lactobacillus casei / metabolism*
  • Male
  • Milk / metabolism
  • Milk / microbiology*
  • Phylogeny
  • Placebos / administration & dosage
  • Probiotics / administration & dosage*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA
  • Stress, Physiological*
  • Students, Medical
  • Treatment Outcome
  • Young Adult


  • DNA, Bacterial
  • DNA, Ribosomal
  • Placebos
  • RNA, Ribosomal, 16S