Lactoferrin up-regulates intestinal gene expression of brain-derived neurotrophic factors BDNF, UCHL1 and alkaline phosphatase activity to alleviate early weaning diarrhea in postnatal piglets.
The molecular mechanisms underlying how dietary lactoferrin (Lf) impacts gut development and maturation and protects against early weaning diarrhea are not well understood. In this study, we supplemented postnatal piglets with an Lf at a dose level of 155 and 285 mg/kg/day from 3 to 38 days following birth. Our findings show that the high dose of Lf up-regulated messenger RNA expression levels of genes encoding brain-derived neurotrophic factor (BDNF) and ubiquitin carboxy-terminal hydrolase L1 (ubiquitin thiolesterase (UCHL1) and, to a lesser extent, glial cell line-derived neurotrophic factor, in the duodenum (P<.05). Piglets in the high and low Lf group had 30% and 7% larger jejunal crypts compared with the control group (P<.05). Escherichia coli 16S rRNA copy number per gram of ascending colon contents was significantly reduced (P=.001), while the copy number of Bifidobacteria and Lactobacillus spp. was not affected. In addition, Lf increased intestinal alkaline phosphatase activity (P<.05) and delayed the onset of food transitional diarrhea, reducing its frequency and duration (P<.05). The incidence of diarrhea in the high and low Lf groups was decreased 54% and 15%, respectively, compared with the control group (P=.035). In summary, these findings provide new evidence that dietary Lf supplementation up-regulated gene expression of BDNF and UCHL1, decreased the colon microbiota of E. coli, improved gut maturation and reduced early weaning diarrhea in piglets. The molecular basis underlying these findings suggests that Lf may enhance gut development and immune function by providing new insight into the gut-brain-microbe axis that has not been previously reported.
School of Medicine, Xiamen University, Xiamen, 361102, China.
Changwei
C
Yang
School of Medicine, Xiamen University, Xiamen, 361102, China.
Xi
X
Zhu
School of Medicine, Xiamen University, Xiamen, 361102, China.
Ni
N
Liu
School of Medicine, Xiamen University, Xiamen, 361102, China.
Yue
Y
Chen
School of Medicine, Xiamen University, Xiamen, 361102, China.
Hexia
H
Gan
School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Biochemistry and Molecular Medicine, University of California School of Medicine, Davis, CA 95616, USA.
Frederic A
FA
Troy
School of Medicine, Xiamen University, Xiamen, 361102, China; School of Animal and Veterinary Science, Charles Sturt University NSW 2678, Australia. Electronic address: biwang@csu.edu.au.
Bing
B
Wang
D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003106:Colon / Q000187:drug effects / Q000382:microbiology; D003967:Diarrhea / Q000178:diet therapy* / Q000235:genetics / Q000517:prevention & control; D019587:Dietary Supplements; D004386:Duodenum / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007422:Intestines / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology; D043322:Lactase / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D034421:Sus scrofa; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects; D014886:Weaning
D019208:Brain-Derived Neurotrophic Factor; D000469:Alkaline Phosphatase; D043322:Lactase; D043222:Ubiquitin Thiolesterase; D007781:Lactoferrin
BDNF; Colonic flora; Gut maturation; IAP; Lactoferrin; Neurotrophins; UCHL1