SFB 852: Nutrition and Intestinal Microbiota - Host Interaction in the Pig
Agriculture, Forestry and Veterinary Medicine
Final Report Abstract
The SFB 852 “Nutrition and intestinal microbiota - host interaction in the pig” was hosted at the Freie Universität Berlin. The objective was to study the interaction of nutritional factors, the intestinal microbiota and the host organism as driving forces of the balance between health, pathophysiologic reactions and disease in pigs as target species. A fully integrative approach with centralised nutritional studies has proved to be successful in unravelling diet-microbiota-host interactions and was backed up by targeted projects addressing specific research topics. The targeted projects were addressing effects of dietary factors on specific interactions with microorganisms, cell culture based work and mouse models for specific questions. Structurally, four project areas covered nutrition-microbiota interactions (A), including innovative models to study functional aspects of the gut microbiome and metabolome. The host reaction was targeted in project area B, including mechanisms how nutritional factors and the microbiota affected digestive processes, gut physiology, the gut associated and general immune system and finally animal health. Project area C included three central projects with organizational, experimental, analytical, and bioinformatic tasks. By integrating the central experimental data we could show new patterns and networks of interactions by using innovative approaches to decode the complex microbiota-host system. This was considered as key element in the proposal and important step going towards systems biology. Training and promotion of young scientists has been successfully achieved by the Integrated Research Training Group in project area D. The Integrated Research Training Group included 26 PhD students and was the fundamental activity for the personal and scientific development of young researchers in a multidisciplinary scientific environment. Further on, the SFB had established a broad spectrum of gender equality measures. The methodological development has allowed substantial progress including a broad spectrum of meta-genomic, -proteomic and -bolomic approaches with central data processing and bioinformatics. The central nutritional experiments focused on the effects of probiotic Enterococcus faecium NCIMB 10415 and the trace element zinc in sows and piglets at the microbial and host domain. The work included physiological and pathophysiologic conditions by using challenge models with bacteria and viruses. We could demonstrate that both nutritional factors had a clear interaction with the intestinal microbiome, gut physiology and the immune system. Key findings on the probiotic E. faecium NCIMB 10415 indicated its role as immune-modulator in pigs, down-regulating inflammatory and immunological responses of the gut and the immune system in general. The probiotic treatment affected the microbial community and the virome composition, indicated by a lower prevalence of rotaviruses and astroviruses. The data suggest an immune modulating effect of E. faecium. No protection could be demonstrated in a challenge mode using Salmonella Typhimurium, in contrast to the probiotic Bacillus cereus var. toyoi. This seemed to be related to an up-regulation of the immune reaction by this probiotic. The key finding in the experiments using the trace element zinc was an impact on the diversity of the intestinal microbiota especially in very young piglets. Zinc affected the composition and metabolism of the intestinal microbiome and the reactivity of the intestinal tissue, but it also had an up now unknown effect on multiresistant bacteria in the intestinal tract. In specific projects, we investigated a genetically modified probiotic producing cystatin, an anti-inflammatory molecule, in mice and the interaction of protein and fiber intake in pigs. The probiotic proved to ameliorate murine experimental colitis and improved intestinal barrier functions in the porcine colon while suppressing post-weaning inflammatory gut reactions. Dietary fiber and protein were tested in a related trial and induced changes in the intestinal microbiota, and had functional consequences in the intestine of pigs. The structure of SFB 852 induced an intensive and transdisciplinary interaction between the different research groups. This is displayed by an effective publication output in the first funding period. The results obtained during the years of the collaborative research centre are considered influential on the scientific understanding of nutritional biology in pigs and allowed to build up new hypotheses on nutrition-host interactions. The link between nutrition and infection medicine is important for the pig as animal species but also as model for nutritional biology. The results generated will further stimulate collaborative research at the Freie Universität Berlin and the partner institutions.
Publications
- (2011) E. coli Nissle 1917 affects Salmonella adhesion to porcine intestinal epithelial cells. PLoS One. 2011 Feb 17;6(2):e14712
Schierack, P., S. Kleta, K. Tedin, J. Tachu Babila, S. Oswald, T. A. Oelschlaeger, R. Hiemann, S. Pätzold, L. H. Wieler
- (2011): Increased dietary zinc oxide changes the bacterial core and enterobacterial composition in the ileum of piglets. J. Anim. Sci. 89: 2430-2439
Vahjen, W., R. Pieper, J. Zentek
- (2012) Enterococcus faecium NCIMB 10415 does not protect interleukin-10 knock-out mice from chronic gut inflammation. Benef. Microbes 3:43-50
Ganesh, B.P., J.F. Richter, M. Blaut, G. Loh
(See online at https://doi.org/10.3920/BM2011.0050) - (2012). Effects of dietary zinc oxide and Enterococcus faecium NCIMB 10415 supplementation on Campylobacter coli level in weaned piglets. Int J Med Microbiol, 302, 56
Bratz K., Gölz G., Alter T., Bücker R., Janczyk P., Noeckler K.
- (2012): Feeding of the probiotic bacterium Enterococcus faecium NCIMB 10415 differentially affects shedding of enteric viruses in pigs. Veterinary Research 43: 58
Kreuzer, S., Machnowska, P., Aßmus, J., Sieber, M., Pieper, R., Schmidt, M.F.G., Brockmann, G.A., Scharek-Tedin, L., Johne, R.
(See online at https://doi.org/10.1186/1297-9716-43-58) - (2012): Fermentable fibre ameliorates fermentable protein-induced changes in microbial ecology but not the mucosal response in the colon of piglets. J. Nutr. 142: 661-667
Pieper, R., S. Kröger, J.F. Richter, J. Wang, L. Martin, J. K. Htoo, D. von Smolinski, W. Vahjen, J. Zentek, A.G. Van Kessel
(See online at https://doi.org/10.3945/jn.111.156190) - (2012): Simultaneous identification of DNA and RNA viruses present in pig faeces using process-controlled deep sequencing. PLoS ONE 7: e34631
Sachsenröder, J., Twardziok, S., Hammerl, J.A., Janczyk, P., Wrede, P., Hertwig, S., Johne, R.
(See online at https://doi.org/10.1371/journal.pone.0034631) - (2013) Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One 8:e74963
Ganesh, B.P., R. Klopfleisch, G. Loh, M. Blaut
(See online at https://doi.org/10.1371/journal.pone.0074963) - (2013) Feeding the probiotic Enterococcus faecium strain NCIMB 10415 specifically reduces Escherichia coli pathotypes adherent to the gut mucosa of piglets. Appl. Environ. Microbiol. 2013 Oct 11. 79(24):7896-904
Bednorz, C., S. Guenther, K. Oelgeschläger, B. Kinnemann, R. Pieper, S. Hartmann, K. Tedin, T. Semmler, K. Neumann, P. Schierack, A. Bethe, L. H. Wieler
- (2013) Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium. PLOS One 8: e79643
Zakrzewski SS, Richter JF, Krug SM, Jebautzke B, Lee IM, Rieger J, Sachtleben M, Bondzio A, Schulzke JD, Fromm M, Günzel D
(See online at https://doi.org/10.1371/journal.pone.0079643) - (2013) The broader context of antibiotic resistance: Zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. Int. J. Med. Microbiol. 303, 396-403
Bednorz, C., S. Guenther, K. Oelgeschläger, B. Kinnemann, R. Pieper, Bednorz, C., K. Oelgeschläger, B. Kinnemann, S. Hartmann, K. Neumann, R. Pieper, A. Bethe, T. Semmler, K. Tedin, P. Schierack, L. H. Wieler, S. Guenther
(See online at https://doi.org/10.1016/j.ijmm.2013.06.004) - (2013). Experimental infection of weaned piglets with Campylobacter coli - Excretion and translocation in a pig colonisation trial. Vet Microbiol 31, 480-484
Bratz, K., Bucker, R., Golz, G., Zakrzewski, S.S., Janczyk, P., Nockler, K., Alter, T.
(See online at https://doi.org/10.1016/j.vetmic.2012.08.016) - (2013): A high level of dietary zinc changes the expression of zinc transporters and metallothionein in jejunal epithelial cells in vitro and in vivo, but does not prevent zinc accumulation in jejunal tissue of piglets. J. Nutr. 143(8): 1205-1210
Martin, L., U. Lodemann, A. Bondzio, E.M. Gefeller, W. Vahjen, J.R. Aschenbach, J. Zentek, R. Pieper
(See online at https://doi.org/10.3945/jn.113.177881) - (2013): Characterization of the effects of Enterococcus faecium on intestinal epithelial transport properties in piglets. J. Anim. Sci. 91 (4): 1707-1718
Klingspor S., H. Martens, D. Caushi, S. Twardziok, J.R. Aschenbach, U. Lodemann
(See online at https://doi.org/10.2527/jas.2012-5648) - (2013): Effects of zinc on epithelial barrier properties and viability in a human and a porcine intestinal cell culture model. Toxicol. In Vitro 27(2): 834-843
Lodemann, U., R. Einspanier, F. Scharfen, H. Martens, A. Bondzio
(See online at https://doi.org/10.1016/j.tiv.2012.12.019) - (2013): Equivalent indels--ambiguous functional classes and redundancy in databases. PLoS One. 2;8(5):e62803
Assmus, J., Kleffe, J., Schmitt, A.O., Brockmann, G.A.
(See online at https://doi.org/10.1371/journal.pone.0062803) - (2013): Gene test to elucidate the ETEC F4ab/F4ac receptor status in pigs. Vet. Microbiol. 162: 293-295
Kreuzer, S., M. Reissmann, G.A. Brockmann
- (2013): High dosage of dietary zinc oxide has no protective effects on weaned pigs infected with Salmonella enterica serovar Typhimurium DT 104. Appl. Environ. Microbiol. 79, 2914-2921
Janczyk, P., S. Kreuzer, J. Assmus, K. Nöckler, G. Brockmann
- (2013): Individual responses of mother sows to a probiotic Enterococcus faecium strain lead to different microbiota composition in their offspring. Benef Microbes. 4: 345-356
Starke, I. C., R. Pieper, K. Neumann, J. Zentek, W. Vahjen
(See online at https://doi.org/10.3920/BM2013.0021) - (2013): New fast cost-effective gene test to get the ETEC F18 receptor status in pigs. Vet. Microbiol. 163: 392-394
Kreuzer, S., M. Reissmann, G.A. Brockmann
(See online at https://doi.org/10.1016/j.vetmic.2012.12.040) - (2013): The impact of high dietary zinc oxide on the development of the intestinal microbiota in weaned piglets. FEMS Microbiol Ecol. 2014 Feb;87(2):416-27
Starke, I. C., Vahjen, W., Pieper, R. Neumann, J. Zentek
- Einspanier and S. Sharbati. (2013): Intestinal Salmonella typhimurium infection leads to miR-29a induced caveolin 2 regulation. PLoS One 8(6): e67300
Hoeke, L., J. Sharbati, K. Pawar, A. Keller, R.
(See online at https://doi.org/10.1371/journal.pone.0067300) - (2014) A transgenic probiotic secreting a parasite immunomodulator for site-directed treatment of gut inflammation. Mol Ther, 22:1730-40
Whelan, R.A., S. Rausch, F. Ebner, D. Günzel, J. F. Richter, N. A. Hering, J. D. Schulzke, A. A. Kühl, A. Keles, P. Janczyk, K. Nöckler, L. H. Wieler, S. Hartmann
(See online at https://doi.org/10.1038/mt.2014.125) - (2014) Diets high in fermentable protein and fiber alter tight junction protein composition with minor effect on barrier function in piglet colon. Br. J. Nutr. 111: 1040-1049
Richter JF, Pieper R, Zakrzewski SS, Günzel D, Schulzke JD, Van Kessel AG
(See online at https://doi.org/10.1017/S0007114513003498) - (2014) α-Haemolysin of E. coli - a mediator of inflammatory activity in the colon. Gut 63, 1893-1901
Bücker, R., E. Schulz, D. Günzel, C. Bojarski, In-Fah M. L., L. John, S. Wiegand, T. Janßen, C. Ewers, L. H. Wieler, U. Dobrindt, L. Beutin, B. Siegmund, H. Troeger, J.-D. Schulzke
(See online at https://doi.org/10.1136/gutjnl-2013-306099) - (2014). Cross-talk between host, microbiome and probiotics: A systems biology approach for analyzing the effects of probiotic Enterococcus faecium NCIMB 10415 in piglets. Mol. Informatics. 33; 171-182
Twardziok, S.O., R. Pieper, J. Aschenbach, C. Bednorz, G.A. Brockmann, M. Fromm, S. Klingspor, S. Kreuzer, U. Lodemann, H. Martens, L. Martin, J.F. Richter, I. Starke, B. Siepert, K. Tedin, L. Scharek-Tedin, W. Vahjen, L. Wieler, S.S. Zakrzewski, J. Zentek, P. Wrede
(See online at https://doi.org/10.1002/minf.201300147) - (2014): A novel lineage transcription factor based analysis reveals differences in T helper cell subpopulation development in infected and intrauterine growth restricted (IUGR) piglets. Dev Comp Immunol, 46:333-40
Ebner, F., S. Rausch, L. Scharek-Tedin, R. Pieper, M. Burwinkel, J. Zentek, S. Hartmann
(See online at https://doi.org/10.1016/j.dci.2014.05.005) - (2014): Arcobacter butzleri induces a pro-inflammatory response in THP-1 derived macrophages and has limited ability for intracellular survival. Int J Med Microbiol 304(8): 1209-1217
Bruegge, J. Z., C. Hanisch, R. Einspanier, T. Alter, G. Golz and S. Sharbati
(See online at https://doi.org/10.1016/j.ijmm.2014.08.017) - (2014): Characterization of CD4+ subpopulations and CD25+ cells in ileal lymphatic tissue of weaned piglets infected with Salmonella Typhimurium with or without Enterococus faecium feeding. Vet. Immunol. Immunopathol. 158, 143-155
Kreuzer, S., J. Rieger, E.M. Strucken, N. Thaben, H. Hünigen, K. Nöckler, P. Janczyk, J. Plendl, G. Brockmann
(See online at https://doi.org/10.1016/j.vetimm.2014.01.001) - (2014): Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection. PLoS One. 9:e87007
Wang, Z., M. Burwinkel, W. Chai, E. Lange, U. Blohm, A. Breithaupt, B. Hoffmann, S. Twardziok, J. Rieger, P. Janczyk, R. Pieper, N. Osterrieder
(See online at https://doi.org/10.1371/journal.pone.0087007) - (2014): Effect of dietary zinc oxide on morphological characteristics, mucin composition and gene expression in the colon of weaned piglets. PLoS One. e91091
Liu, P., R. Pieper, J. Rieger, W. Vahjen, R. Davin, J. Plendl, W. Meyer, J. Zentek
(See online at https://doi.org/10.1371/journal.pone.0091091) - (2014): Elevated dietary zinc oxide levels do not have a substantial effect on porcine reproductive and respiratory syndrome virus (PPRSV) vaccination and infection. Virol. J. 11:140
Chai, W., Z. Wang, P. Janczyk, S. Twardziok, U. Blohm, N. Osterrieder, M. Burwinkel
(See online at https://doi.org/10.1186/1743-422X-11-140) - (2014): Enterococcus faecium NCIMB 10415 supplementation affects intestinal immune-associated gene expression in post-weaning piglets. Vet. Immunol. Immunopathol. 157, 65-77
Siepert, B., N. Reinhardt, S. Kreuzer, A. Bondzio, S. Twardziok, G. Brockmann, K. Nöckler, I. Szabó, P. Janczyk, R. Pieper, K. Tedin
(See online at https://doi.org/10.1016/j.vetimm.2013.10.013) - (2014): High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets. BMC Vet. Res. 10:75
Chai, W., S.S. Zakrzewski, D. Günzel, R. Pieper, Z. Wang, S. Twardziok, P. Janczyk, N. Osterrieder, M. Burwinkel
(See online at https://doi.org/10.1186/1746-6148-10-75) - (2014): The general composition of the faecal virome of pigs depends on age, but not on feeding with a probiotic bacterium. PLoS ONE, 9, e88888
Sachsenröder, J., Twardziok, S.O., Scheuch, M., Johne, R.
(See online at https://doi.org/10.1371/journal.pone.0088888) - (2015): Down-regulation of MCT1 gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling. Br. J. Nutr. 113: 610-617
Villodre Tudela, C., C. Boudry, F. Stumpff, J.R. Aschenbach, W. Vahjen, J. Zentek, R. Pieper
(See online at https://doi.org/10.1017/S0007114514004231) - (2015): Impact of high dietary zinc on zinc accumulation, enzyme activity and proteomic profiles in the pancreas of piglets. J. Trace Elem. Med. Biol. 30: 30-36
Pieper, R., L. Martin, N. Schunter, C. Weise, R. Klopfleisch, J. Zentek, R. Einspanier, A. Bondzio
(See online at https://doi.org/10.1016/j.jtemb.2015.01.008) - (2015): Probiotic treatment decreases the number of CD14-expressing cells in porcine milk which correlates with several immune parameters in the piglets. Frontiers Immunol. 6; 108
Scharek-Tedin, L., S. Kreuzer, S.O. Twardziok, B. Siepert, R. Klopfleisch, K. Tedin, J. Zentek, R. Pieper
(See online at https://doi.org/10.3389/fimmu.2015.00108) - (2015): Regulation of intracellular Zn homeostasis in two intestinal epithelial cell models at various maturation time points. J. Physiol. Sci.
Gefeller, E.M., A. Bondzio, J.R. Aschenbach, H. Martens, R. Einspanier, F. Scharfen, J. Zentek, R. Pieper, U. Lodemann
(See online at https://doi.org/10.1007/s12576-015-0369-4)
