Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-26T19:01:13.408Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Published online by Cambridge University Press:  20 February 2014

M. Colombo ,
D. Priori ,
G. Gandolfi ,
G. Boatto ,
M. Nieddu ,
P. Bosi  and
P. Trevisi
M. Colombo
Affiliation:
Dipartimento di Scienze e Tecnologie Agroalimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy
D. Priori
Affiliation:
Dipartimento di Scienze e Tecnologie Agroalimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy
G. Gandolfi
Affiliation:
Dipartimento di Scienze e Tecnologie Agroalimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy
G. Boatto
Affiliation:
Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy
M. Nieddu
Affiliation:
Dipartimento di Chimica e Farmacia, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy
P. Bosi*
Affiliation:
Dipartimento di Scienze e Tecnologie Agroalimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy
P. Trevisi
Affiliation:
Dipartimento di Scienze e Tecnologie Agroalimentari, Università di Bologna, Via F.lli Rosselli 107, 42123 Reggio Emilia, Italy
*
†E-mail: [email protected]
Get access

Abstract

Thymol is the most common molecule in thyme and has been proposed as an oral alternative to antibiotics in the feed of pigs and broilers. The knowledge of the in vivo physiological effects of thymol on tissues is limited, particularly its impact on the gastric mucosa, where it is primarily absorbed when it is orally supplied. In this study, thymol (TH, 50 mg/ kg BW) or a placebo (CO) was introduced directly into the stomach of 8 weaned pigs that were slaughtered 12 h later and sampled for gastric oxyntic and pyloric mucosa. The analysis of whole transcript expression was performed using Affymetrix© Porcine Gene 1.1 ST array strips. Affymetrix Transcripts IDs were associated with 13 406 human gene names based on Sus scrofa Ensemble. Gene Set Enrichment Analysis was performed, comparing TH and CO pigs. For each gene set, the normalized enrichment score (NES) was defined as significant when the false discovery rate % was <25 and the P-value of NES was <0.05. In response to TH, 72 and 19 gene sets were significantly enriched in the oxyntic and pyloric mucosa, respectively. Several gene sets involved in mitosis and its regulation ranked near the top, primarily in the oxyntic mucosa; the gene set DIGESTION ranked first and ninth in the pyloric and oxyntic mucosa, respectively. Within this group, somatostatin (SST), SST receptors, peptide transporter 1 (SLC15A1) and calpain 9 (gastrointestinal tract-specific calpain) were the most strongly upregulated genes. Thymol reduced the enrichment of 120 and 59 gene sets in the oxyntic and pyloric mucosa, respectively. Several gene sets related to ion transport and channeling and aqueous pores across membranes, including short transient receptor potential (TRP) channel 4, potassium voltage-gated channel members 1 and 2, and ryanodine receptors 2 and 3, were less enriched. The downregulation of these genes sensitive to thymol in vitro could depend on the thymol dose and contact with the gastric tissues that causes an adaptive response with their reduced activation. Conversely, the activation of the TRPA1 gene (ranked 1072 and 128 among all the genes in the oxyntic and pyloric mucosa, respectively) indicates the involvement of another TRP-regulating cellular calcium storage. In conclusion, the stimulation of gastric proliferative activity and the control of digestive activity by thymol can influence positively gastric maturation and function in the weaned pigs. These properties should be considered in addition to thymol’s antimicrobial properties when supplementation of this molecule in feed is evaluated.

Keywords

gene expressionpigstomachthymol
Type
Full Paper
Information
animal , Volume 8 , Issue 5 , May 2014 , pp. 786 - 791
Copyright
© The Animal Consortium 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andersson, EL, Hernell, O, Bläckberg, L, Fält, H and Lindquist, S 2011. BSSL and PLRP2: key enzymes for lipid digestion in the newborn examined using the Caco-2 cell line. Journal of Lipid Research 52, 1949–1956.Google Scholar
Archana, PR, Nageshwar Rao, B and Satish Rao, BS 2011. Modulation of gamma-ray-induced genotoxic effect by thymol, a monoterpene phenol derivative of cymene. Integrative Cancer Therapies 10, 374–383.CrossRefGoogle ScholarPubMed
Bauer, E, Jakob, S and Mosenthin, R 2005. Principles of physiology of lipid digestion. Asian-Australasian Journal of Animal Sciences 18, 282–295.Google Scholar
Birnbaumer, L 2009. The TRPC class of ion channels: a critical review of their roles in slow, sustained increases in intracellular Ca2+ concentrations. Annual Review of Pharmacology and Toxicology 49, 395–426.Google Scholar
Boudry, G and Perrier, C 2008. Thyme and cinnamon extracts induce anion secretion in piglet small intestine via cholinergic pathways. Journal of Physiology and Pharmacology 59, 543–552.Google Scholar
Carrière, F, Barrowman, JA, Verger, R and Laugier, R 1993. Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterology 105, 876–888.Google Scholar
Colombo, M, Trevisi, P, Gandolfi, G and Bosi, P 2012. Assessment of the presence of chemosensing receptors based on bitter and fat taste in the gastrointestinal tract of young pig. Journal of Animal Science 90, 128–130.CrossRefGoogle ScholarPubMed
Darcel, NP, Liou, AP, Tome, D and Raybould, HE 2005. Activation of vagal afferents in the rat duodenum by protein digests requires PepT1. Journal of Nutrition 135, 1491–1495.CrossRefGoogle ScholarPubMed
Goebel, M, Stengel, A, Lambrecht, NW and Sachs, G 2011. Selective gene expression by rat gastric corpus epithelium. Physiological Genomics 43, 237–254.Google Scholar
Janczyk, P, Trevisi, P, Souffrant, WB and Bosi, P 2008. Effect of thymol on microbial diversity in the porcine jejunum. International Journal of Food Microbiology 126, 258–261.Google Scholar
Junnila, S, Kokkola, A, Mizuguchi, T, Hirata, K, Karjalainen‐Lindsberg, ML, Puolakkainen, P and Monni, O 2010. Gene expression analysis identifies over‐expression of CXCL1, SPARC, SPP1, and SULF1 in gastric cancer. Genes, Chromosomes and Cancer 49, 28–39.Google Scholar
Kaji, I, Karaki, S and Kuwahara, A 2011. Effects of luminal thymol on epithelial transport in human and rat colon. American Journal of Physiology-Gastrointestinal and Liver Physiology 300, G1132–G1143.Google Scholar
Kaji, I, Yasuoka, Y, Karaki, SI and Kuwahara, A 2012. Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon. American Journal of Physiology-Gastrointestinal and Liver Physiology 302, G690–G701.Google Scholar
Khan, R, Naz, S, Nikousefat, Z, Tufarelli, V and Laudadio, V 2012. Thymus vulgaris: alternative to antibiotics in poultry feed. World’s Poultry Science Journal 68, 401–408.Google Scholar
Kohlert, C, Schindler, G, März, RW, Abel, G, Brinkhaus, B, Derendorf, H, Gräfe, EU and Veit, M 2002. Systemic availability and pharmacokinetics of thymol in humans. Journal of Clinical Pharmacology 42, 731–737.CrossRefGoogle ScholarPubMed
Lallès, JP, Bosi, P, Janczyk, P, Koopmans, SJ and Torrallardona, D 2009. Impact of bioactive substances on the gastrointestinal tract and performance of weaned piglets: a review. Animal 3, 1625–1643.Google Scholar
Lee, SP, Buber, MT, Yang, Q, Cerne, R, Cortes, RY, Sprous, DG and Bryant, RW 2008. Thymol and related alkyl phenols activate the hTRPA1 channel. British Journal of Pharmacology 153, 1739–1749.CrossRefGoogle ScholarPubMed
Mazzoni, M, Bosi, P, De Sordi, N and Giovanna Lalatta-Costerbosa, G 2011. Distribution, organization and innervation of gastric MALT in conventional piglet. Journal of Anatomy 219, 611–621.CrossRefGoogle ScholarPubMed
Mazzoni, M, De Giorgio, R, Latorre, R, Vallorani, C, Bosi, P, Trevisi, P, Barbara, G, Stanghellini, V, Corinaldesi, R, Forni, M, Faussone-Pellegrini, MS, Sternini, C and Clavenzani, P 2013. Expression and regulation of α-transducin in the pig gastrointestinal tract. Journal of Cellular and Molecular Medicine 17, 466–474.Google Scholar
Michiels, J, Missotten, J, Dierick, N, Fremaut, D, Maene, P and De Smet, S 2008. In vitro degradation and in vivo passage kinetics of carvacrol, thymol, eugenol and trans-cinnamaldehyde along the gastrointestinal tract of piglets. Journal of the Science of Food and Agriculture 88, 2371–2381.Google Scholar
Nguyen, HTT, Dalmasso, G, Powell, KR, Yan, Y, Bhatt, S, Kalman, D, Sitaraman, SV and Merlin, D 2009. Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response. Gastroenterology 137, 1435–1447.Google Scholar
Ortar, G, Morera, L, Moriello, AS, Morera, E, Nalli, M, Marzo, VD and Petrocellis, LD 2012. Modulation of thermo-transient receptor potential (thermo-TRP) channels by thymol-based compounds. Bioorganic & Medicinal Chemistry Letters 22, 3535–3539.CrossRefGoogle ScholarPubMed
Sárközi, S, Almássy, J, Lukács, B, Dobrosi, N, Nagy, G and Jóna, I 2007. Effect of natural phenol derivatives on skeletal type sarcoplasmic reticulum Ca2+-ATPase and ryanodine receptor. Journal of Muscle Research and Cell Motility 28, 167–174.CrossRefGoogle ScholarPubMed
Shimakura, J, Terada, T, Saito, H, Katsura, T and Inui, KI 2006a. Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor α. American Journal of Physiology-Gastrointestinal and Liver Physiology 291, G851–G856.CrossRefGoogle ScholarPubMed
Shimakura, J, Terada, T, Shimada, Y, Katsura, T and Inui, KI 2006b. The transcription factor Cdx2 regulates the intestine-specific expression of human peptide transporter 1 through functional interaction with Sp1. Biochemical Pharmacology 71, 1581–1588.Google Scholar
Shu, HJ, Takeda, H, Shinzawa, H, Takahashi, T and Kawata, S 2002. Effect of lipopolysaccharide on peptide transporter 1 expression in rat small intestine and its attenuation by dexamethasone. Digestion 65, 21–29.Google Scholar
Trevisi, P, Merialdi, G, Mazzoni, M, Casini, L, Tittarelli, C, De Filippi, S, Minieri, L, Lalatta-Costerbosa, G and Bosi, P 2007. Effect of dietary addition of thymol on growth, salivary and gastric function, immune response, and excretion of Salmonella enterica serovar Typhimurium, in weaning pigs challenged with this microbe strain. Italian Journal of Animal Science 6, 374–376.CrossRefGoogle Scholar
US Environmental Protection Agency 2009. Thymol; exemption from the requirement of a tolerance. Retrieved April 20, 2013, from http://www.epa.gov/fedrgstr/EPA-PEST/2009/March/Day-25/p6262.pdf Google Scholar
Uyanoglu, M, Canbek, M, Aral, E and Husnu Can Baser, K 2008. Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 15, 226–229.Google Scholar
Xu, H, Delling, M, Jun, JC and Clapham, DE 2006. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nature Neuroscience 9, 628–635.Google Scholar
Yamada, K, Murata, T, Kobayashi, K, Miyase, T and Yoshizaki, F 2010. A lipase inhibitor monoterpene and monoterpene glycosides from Monarda punctata. Phytochemistry 71, 1884–1891.Google Scholar