Morphological and molecular response of small intestine to lactulose and hydrogen-rich water in female piglets fed Fusarium mycotoxins contaminated diet

Background: Following the intake of Fusarium mycotoxin-contaminated feed, small intestines may be exposed to high levels of toxic substances that can potentially damage intestinal functions in livestock. It is well known that Fusarium mycotoxins will lead a breakdown of the normally impeccable epithelial barrier, resulting in the development of a "leaky" gut. H₂ administration with different methods has been proved definitely potentials to prevent serious intestinal diseases. The goal of this study is to investigate the roles of lactulose (LAC) and hydrogen-rich water (HRW) in preventing intestinal dysfunction in piglets fed Fusarium mycotoxin-contaminated feed.

Methods: A total of 24 female piglets were evenly assigned to 4 groups: negative control (NC) group, mycotoxin-contaminated (MC) feed group, MC feed with LAC treatment (MC + LAC), and MC feed with HRW treatment (MC + HRW), respectively. Piglets in the NC group were fed uncontaminated control diet, while remaining piglets were fed Fusarium mycotoxin-contaminated diet. For the NC and MC groups, 10 mL/kg body weight (BW) of hydrogen-free water (HFW) was orally administrated to piglets twice daily; while in the MC + LAC and MC + HRW groups, piglets were treated with the same dose of LAC solution (500 mg/kg BW) and HRW twice daily, respectively. On d 25, serum was collected and used for biochemical analysis. Intestinal tissues were sampled for morphological examination as well as relative genes and protein expression analysis.

Results: Our data showed that Fusarium mycotoxins induced higher serum diamine oxidase (DAO) activities (P < 0.05), D-lactic acid levels (P < 0.01), and endotoxin status (P < 0.01), lower villus height (P < 0.01) and ratio of villus height to crypt depth (P < 0.05) in small intestine, greater apoptosis index and higher mRNA expression related to tight junctions (P < 0.05). In addition, the distribution and down-regulation of claudin-3 (CLDN3) protein in the small intestinal was also observed. As expected, oral administrations of HRW and LAC were found to remarkably provide beneficial effects against Fusarium mycotoxin-induced apoptosis and intestinal leaking. Moreover, either HRW or LAC treatments were also revealed to prevent abnormal intestinal morphological changes, disintegrate tight junctions, and restore the expression and distribution of CLDN3 protein in the small intestinal mucosal layer in female piglets that were fed Fusarium mycotoxins contaminated diet.

Conclusions: Our data suggest that orally administrations of HRW and LAC result in less Fusarium mycotoxin-induced apoptosis and leak in the small intestine. Either HRW or LAC treatments could prevent the abnormal changes of intestinal morphology and molecular response of tight junctions as well as restore the distribution and expression of CLDN3 protein of small intestinal mucosa layer in female piglets that were fed Fusarium mycotoxins contaminated diet.