title: 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.
abstract: 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.
  
  
  
  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.
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Kato-Kataoka
authors.affiliation: Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Takada
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kikuchi-Hayakawa
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Suda
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Gondo
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsuki
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kushiro
authors.affiliation: Development Department, Yakult Honsha Co., Ltd., Higashi-Shimbashi, Minato, Tokyo, Japan.
authors.forename: Ryoutaro
authors.initials: R
authors.lastname: Hoshi
authors.affiliation: Development Department, Yakult Honsha Co., Ltd., Higashi-Shimbashi, Minato, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.affiliation: Development Department, Yakult Honsha Co., Ltd., Higashi-Shimbashi, Minato, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Yakult Central Institute, Izumi, Kunitachi, Tokyo, Japan koji-miyazaki@yakult.co.jp.
authors.forename: Kouji
authors.identifier: 0000-0001-7489-6514
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwano
authors.affiliation: Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Tokushima, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
mesh_terms: D000328:Adult; D000818:Animals; D058448:Biota / Q000187:drug effects*; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D005285:Fermentation; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology*; D006801:Humans; D007780:Lacticaseibacillus casei / Q000378:metabolism*; D008297:Male; D008892:Milk / Q000378:metabolism / Q000382:microbiology*; D010802:Phylogeny; D010919:Placebos / Q000008:administration & dosage; D019936:Probiotics / Q000008:administration & dosage*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013312:Stress, Physiological; D013337:Students, Medical; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D010919:Placebos; D012336:RNA, Ribosomal, 16S