To explore the protective effect of Fructooligosaccharides (FOS) against Enterotoxigenic Escherichia coli (ETEC)-induced
inflammation and intestinal injury, twenty-four weaned pigs were randomly assigned into three groups: (1) non-challenge (CON, fed with basal diet), (2) ETEC-challenge (ECON, fed with basal diet), and (3) ETEC challenge + FOS treatment (EFOS, fed with basal diet plus 2.5 g kg-1 FOS). On day 19, the CON group was orally infused with sterilized culture while pigs in the ECON group and EFOS group were orally infused with ETEC (2.5 × 1011 colony-forming units). After 3 days, pigs were slaughtered for sample collection. We showed that ETEC challenge significantly reduced average daily gain (ADG); however, FOS improved the ADG (P < 0.05), apparent digestibility of crude
protein (CP), gross energy (GE), and ash and reduced the
diarrhea incidence (P < 0.05). FOS reduced plasma concentrations of IL-1β and TNF-α and down-regulated (P < 0.05) the
mRNA expression of
IL-6 and TNF-α in the jejunum and ileum as well as IL-1β and TNF-α in the duodenum. The concentrations of plasma
immunoglobulin A (
IgA),
immunoglobulin M (
IgM) and secreted
IgA (
SIgA) in the jejunum (P < 0.05) were elevated. Interestingly, FOS elevated the villus height in the duodenum, and elevated the ratio of villus height to crypt depth in the duodenum and ileum in the EFOS group pigs (P < 0.05). Moreover, FOS increased
lactase activity in the duodenum and ileum (P < 0.05). The activities of
sucrase and
alkaline phosphatase (AKP) were higher in the EFOS group than in the ECON group (P < 0.05). Importantly, FOS up-regulated the expressions of critical genes in intestinal epithelium function such as zonula occludens-1 (ZO-1), L-type
amino acid transporter-1 (LAT1), and cationic
amino acid transporter-1 (CAT1) in the duodenum and the expressions of ZO-1 and
glucose transporter-2 (GLUT2) in the jejunum (P < 0.05). FOS also up-regulated the expressions of
occludin,
fatty acid transporter-4 (FATP4),
sodium glucose transport protein 1 (SGLT1), and GLUT2 in the ileum (P < 0.05). FOS significantly increased the concentrations of
acetic acid,
propionic acid and
butyric acid in the cecal digesta. Additionally, FOS reduced the populations of Escherichia coli, but elevated the populations of Bacillus and Bifidobacterium in the caecal digesta (P < 0.05). These results suggested that FOS could improve the growth performance and intestinal health in weaned pigs upon ETEC challenge, which was associated with suppressed inflammatory responses and improved intestinal epithelium functions and microbiota.