Direct research on gut microbiota for understanding its role as 'an important organ' in human individuals is difficult owing to its vast diversity and host specificity as well as ethical concerns. Transplantation of human gut microbiota into surrogate hosts can significantly facilitate the research of human gut ecology, metabolism and immunity but rodents-based model provides results with low relevance to humans. A new human flora-associated (HFA) piglet model was hereby established taking advantage of the high similarity between pigs and humans with respect to the anatomy, physiology and metabolism of the digestive system. Piglets were delivered via cesarean section into a SPF-level barrier system and were inoculated orally with a whole fecal suspension from one healthy 10-year-old boy. The establishment and composition of the intestinal microbiota of the HFA piglets were analyzed and compared with that of the human donor using enterobacterial repetitive intergenic consensus sequence-PCR fingerprinting-based community DNA hybridization, group-specific PCR-temperature gradient gel electrophoresis and real-time PCR. Molecular profiling demonstrated that transplantation of gut microbiota from a human to germfree piglets produced a donor-like microbial community with minimal individual variation. And the microbial succession with aging of those ex-germfree piglets was also similar to that observed in humans. This HFA model provides a significantly improved system for research on gut ecology in human metabolism, nutrition and drug discovery.
Recent studies have demonstrated that lactobacilli or their cell components can improve certain immune function in animals. The aim of this study is to investigate the effects of porcine lactobacilli on the intestinal mucosal immunity of piglets. Neonatal piglets were used as a model and were orally administrated with Lactobacillus salivarius B1 isolated from the duodenal mucosa of a healthy piglet. The feces of the piglets were collected on days 7, 14, and 21 for intestinal microflora analysis. On day 28, the piglets were sacrificed, and their intestinal mucosa samples were immediately collected to investigate the changes in intestinal morphological and immunocompetent cells. Finally, the expression of cytokines and TLRs was detected in the different intestinal segments. The results indicate that L. salivarius B1 can partially ameliorate the microflora of the feces and increase the number of intestinal immunocompetent cells, as the intraepithelial lymphocyte (P < 0.05), and the IgA-producing cells (P < 0.01) in the lactobacilli-treated group were all increased compared with those in the control group. Enhanced expression of the cytokine IL-6 gene was also observed in the ileum (P < 0.05). Moreover, L. salivarius B1 can also upregulate the expression of TLR2 in the intestinal tract at the gene and protein levels (P < 0.05). The results demonstrate that L. salivarius B1 is beneficial for the maturation of the intestinal mucosal immune system and elicited local immunomodulatory activities. In addition, the modulatory effects of L. salivarius B1 on mucosal immunity mainly depend on its extracellular components.
We first used human flora-associated (HFA) piglets, a significantly improved model for research on human gut microbiota, to study the effects of short-chain fructo-oligosaccharides (scFOS) on the gut bacterial populations. Ten neonatal HFA piglets were assigned to receive basal diets alone or supplemented with scFOS (0.5 g/kg body weight/day) from 1 to 37 days after birth (DAB). The impact of scFOS on the fecal bacterial populations of the piglets before (12 DAB), during (17 DAB), and after (25 and 37 DAB) weaning were monitored by PCR-denaturing gradient gel electrophoresis and real-time quantitative PCR. The Bifidobacterium genus was stimulated consistently, except during weaning, confirming the bifidogenic property of scFOS. At 12 DAB, the Clostridium leptum subgroup was decreased and two unknown Bacteroides-related species were increased; at 25 DAB, the C. leptum subgroup and Subdoligranulum variabile-like species were elevated, whereas one unknown Faecalibacterium-related species was suppressed; and at 37 DAB, the Bacteroides genus was decreased. The results showed that effects of scFOS on non-bifidobacteria varied at different developmental stages of the animals, warranting further investigation into the host-development-related effects of prebiotics on the gut microbiota and the host physiology using the HFA piglets as a model for humans.
Human flora‐associated (HFA) piglet model was established to examine the effects of gut microbes from a different donor species on the intestinal morphology and mucosal immunity. Newborn germ‐free piglets, obtained by caesarean section, were orally inoculated with a human and a porcine faecal suspension, and artificially fed to establish a HFA group (n = 7) and pig flora‐associated (PFA) group (n = 7), respectively. All pigs were killed 6 weeks later. Tissue samples from duodenum, jejunum, ileum and colon were collected and studied by histochemistry and immunohistochemistry methods for intestinal morphological analyses and detection of immunocompetent cells. In summary, both groups of pigs performed well but HFA pigs had a somewhat better daily weight gain, and their jejunal villus height and crypt depth were significantly higher. In comparison with PFA pigs, the number of intraepithelial lymphocytes in jejunum was lower but the number of goblet cells containing neutral mucins was significantly increased in HFA pigs. No difference was observed in the number of mast cells. The areas of IgA producing cells and CD4+ T cells in the jejunum and IgG producing cells in the small intestine were significantly higher in HFA pigs. However, the areas of MHC class II expressing cells were significantly increased in the duodenum and colon. Additionally, the amount of Bifidobacteria spp. was significantly higher in HFA pigs. This study confirms that the composition of gut microbes differentially affects the host intestinal mucosal immunity and suggests that commensal bacteria have great effects on intestinal health and development.
Human breast milk Streptococcus spp. are transferred to infant guts via breast feeding, but their effects on the gut microbiota and immunity remain unclear. In this study, we characterized gut microbiota and immune modulatory properties of human breast milk S. salivarius F286 and S. parasanguinis F278 that had been shown to be able to colonize gut. The two Streptococcus strains were orally administered to mouse pups individually at 1 × 107 cells/day from postnatal Days 1 to 21. At postnatal week 3 (the weaning period), S. salivarius F286 reduced the colonic microbiota α-diversity, increased 21 amplicon sequence variants (ASVs), including bacteria from Akkermansia, Intestinimonas, and Lachnospiraceae, and decreased 52 ASVs, including bacteria from Eubacterium, Bifidobacterium, Escherichia-Shigella, and Turicibacter; however, S. parasanguinis F278 didn't change the colonic microbiota. Both Streptococcus strains reduced the ileal mRNA expression of cytokine/transcription factor representatives of T helper (Th) cells, including IFN-γ (Th1), Gata3 (Th2), and TGF-β (Treg) in 2-week-old suckling mice, and promoted the ileal expression of Foxp3 and TGF-β, which are representatives of anti-inflammatory Treg cells, in 3-week-old weaning mice. The two Streptococcus strains exhibited anti-inflammatory potential when incubated in vitro with human peripheral blood mononuclear cells and TNF-α-treated gut epithelial HT29 cells. In C. elegans, both strains activated immune response genes, which was associated with their lifespan-prolonging effects. Our results suggest that S. salivarius F286 and S. parasanguinis F278 may exert regulatory (anti-inflammatory) roles in gut immunity and S. salivarius F286 can modulate gut microbiota, and highlight the probiotic potential of milk S. salivarius and S. parasanguinis strains.
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