Gene signature: a novel approach to assess the effects of gut health-promoting substances

Abstract

Public concern over the contribution of dietary antibiotics used in animal production to the development of antibiotic-resistant bacteria has increased the interest in so-called (gut) health-promoting substances, which include herbal products, as an alternative approach to in-feed antibiotics. In order to investigate the effects and effectiveness of health-promoting herbal products in farm animals, 3 different oregano-containing products had been tested in open feeding trials with fattening pigs. Clinical observations in these farm trials showed positive effects on growth and/or feed conversion as a trend.

In order to find a possible explanation for these observed slightly positive effects, available information about in vitro, ex vivo and in vivo experiments conducted with Origanum vulgare, carvacrol and thymol on bacterial strains of porcine origin, pig tissue and pigs themselves was assembled. Origanum vulgare and its main compounds carvacrol and thymol are thought to affect gut health on account of their antimicrobial activities, which might cause a subtle shift in the divers and complex microflora composition by changes in the metabolic activity and/or amount of one or more bacterial species. The literature review revealed that at effective antimicrobial concentration ranges cell proliferation and gut barrier function are not affected, and despite possible alterations by ingredients of pig diets, and variable physiologic conditions in the gut of pigs, antimicrobial activity has been denoted in vivo. However, it is often neglected that for the interpretation of the relevance of in vitro effects for in vivo results and clinical efficacy, knowledge in pharmacokinetics and mechanisms of action regarding antimicrobial and other gut health-promoting effects are inevitable.

Another aim of the research project was to verify the two formulated hypotheses of how (gut) health-promoting substances might exert their effects, by identification of biomarkers that may serve two quantify health in the healthy animals of the conducted feeding trials. Herbal products might exert indirect effects on the liver by stabilizing the gut flora and intestinal barrier and thus decrease the ‘toxic burden’ of the liver, and they also might exert direct effects on the liver after absorption in the gastrointestinal tract. Therefore, expression levels of genes of pathways involved in oxidative stress and inflammation - assembled in a so-called gene-signature - were analyzed in liver tissue samples using quantitative real-time RT-PCR. Changes in relative expression levels of genes analyzed in this research project showed that pathways regulated by the transcription factors Nrf2, NF-κB, HSF1, and HIF1 are influenced in livers of pigs fed the tested herbal products, and hence suggest that these products improved the balance between cellular stressors and cellular defence capacity in the liver. The results are in line with the expected effects of Origanum vulgare. However, further experiments should include an analysis of the gut microbiota to confirm the hypothesis that the antimicrobial effects of Origanum vulgare contribute to the improvement of gut flora homeostasis.