The Potential Mechanism To Alleviate Constipation With Fermented Milk Containing Lactobacillus Casei Zhang And Bifidobacterium Animalis Subsp.lactis V9

Constipation is a type of multi-factor gastrointestinal disorder characterized by inability or discomfort to perform defecation regularly.Studies suggested that probiotics and fermented milk could improve defecation condition in constipated patients.However,the mechanism of probiotics and fermented milk on constipation remains poorly understood.To investigate the machanism of fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis subsp.lactis V9(LB-PFM)on constipation,26 volunteers with functional constipation symptoms were recruited and provided with LB-PFM(200g/day)for 4 weeks,and the effects of LB-PFM on constipated subjects from the clinical symptoms,cytokines in serum samples,metagenomics in stool samples,metabolomics in both serum and stool smples were evaluated.After 4-weeks intake of LB-PFM,defecation frequency(P=0.03),incomplete defecation(P=0.19×10-4),defecation time(P=0.0014),defecation pain(P=0.012),and straining during defecation(P=0.5×10-6)were improved significantly.Pro-inflammatory cytokine C-reactive protein(CRP,P=0.031)and lipopolysaccharides(LPS,P=0.002)decreased significantly and the LPS binding protein(LBP,P=0.028)and Interleukin-10(IL-10,P=0.015)increased significantly.Metagenomics results showed that the LB-PFM had no significant influence on neither ?-nor ?-diversity,but 11 significantly differential bacteria including Bifidobacterium animalis(P=0.001),Streptococcus thermophilus(P=0.013),Lactobacillus acidophilus(P=0.027)and other 8 species were found;in addition,the dominant Bifidobacteria were changed after LB-PFM consuming:the dominant Bifidobacterium bifidum,Bifidobacterium breve or Bifidobacterium catenulatum was instead of Bifidobacterium animalis or Bifidobacterium adolescentis,among which the Bifidobacterium animalis was significantly positive correlated to defecation frequency(r=0.45,P=0.03).From the metabolomic analysis,after LB-PFM consuming De novo fatty acid biosynthesis and Vitamin E metabolism were identified as significantly changed metabolic pathway in the stool samples,while Bile acid biosynthesis,Xenobiotics metabolism,Vitamin C metabolism,Ascorbate metabolism,Carnitine shuttle and Tryptophan metabolism were identified as significantly altered metabolic pathway in the serum samples.At the same time,we found acylcarnitine,located on the Carnitine shuttle pathway,increased significantly in the serum samples after LB-FPM consuming and had positive correlation to defecation frequency(r=0.815,P=0.016).Thus,it was supposed that LB-PFM consumig may contribute to alleviation of constipation symptoms by improving gut motility through fine-tuning gastrointestinal microbiota and increasing Bifidobacterium animalis,fighting inflammation as well as regulating metabolic pathways and energy metabolism.The present study laid the foundation to the mechanism of constipation-alleviating with probiotic fermented milk and provided a new idea for the constipation treatment.