AUTHOR=Myhill Laura J. , Stolzenbach Sophie , Hansen Tina V. A. , Skovgaard Kerstin , Stensvold C. Rune , Andersen Lee O'Brien , Nejsum Peter , Mejer Helena , Thamsborg Stig M. , Williams Andrew R. 

TITLE=Mucosal Barrier and Th2 Immune Responses Are Enhanced by Dietary Inulin in Pigs Infected With Trichuris suis

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02557

DOI=10.3389/fimmu.2018.02557

ISSN=1664-3224

ABSTRACT=<p>Diet composition may play a crucial role in shaping host immune responses and commensal gut microbiota populations. Bioactive dietary components, such as inulin, have been extensively studied for their bioactive properties, particularly in modulating gut immune function and reducing inflammation. It has been shown that colonization with gastrointestinal parasitic worms (helminths) may alleviate chronic inflammation through promotion of T-helper cell type (Th) 2 and T-regulatory immune responses and alterations in the gut microbiome. In this study, we investigated if dietary inulin could modulate mucosal immune function in pigs during colonization with the porcine whipworm <italic>Trichuris suis</italic>. <italic>T. suis</italic> infection induced a typical Th2-biased immune response characterized by transcriptional changes in Th2- and barrier function-related genes, accompanied by intestinal remodeling through increased epithelial goblet and tuft cell proliferation. We observed that inulin also up-regulated Th2-related immune genes (<italic>IL13, IL5</italic>), and suppressed Th1-related pro-inflammatory genes (<italic>IFNG, IL1A, IL8</italic>) in the colon. Notably, inulin augmented the <italic>T. suis</italic>-induced responses with increased transcription of key Th2 and mucosal barrier genes (e.g., <italic>IL13, TFF3</italic>), and synergistically suppressed pro-inflammatory genes, such as <italic>IFNG</italic> and <italic>CXCL9</italic>. 16S rRNA sequencing of proximal colon digesta samples revealed that inulin supplementation reduced the abundance of bacterial phyla linked to inflammation, such as Proteobacteria and Firmicutes, and simultaneously increased Actinobacteria and Bacteroidetes. Interestingly, pigs treated with both inulin and <italic>T. suis</italic> displayed the highest Bacteroidetes: Firmicutes ratio and the lowest gut pH, suggesting an interaction of diet and helminth infection that stimulates the growth of beneficial bacterial species. Overall, our data demonstrate that <italic>T. suis</italic> infection and inulin co-operatively enhance anti-inflammatory immune responses, which is potentially mediated by changes in microbiota composition. Our results highlight the intricate interactions between diet, immune function and microbiota composition in a porcine helminth infection model. This porcine model should facilitate further investigations into the use of bioactive diets as immunomodulatory mediators against inflammatory conditions, and how diet and parasites may influence gut health.</p>