Dietary Proanthocyanidins Exert Localized Immunomodulatory Effects in Porcine Pulmonary and Gastrointestinal Tissues during Ascaris suum-induced Type 2 inflammation

Bioactive dietary components may considerably influence intestinal health and resistance to enteric disease. Proanthocyanidins (PAC) are dietary polyphenols with putative health-promoting activity that have been increasingly studied for their anti-inflammatory and immunomodulatory effects. However, whether dietary PAC can regulate type-2 immune function and inflammation at mucosal surfaces remains unclear. Here, we investigated whether diets supplemented with purified PAC modulated pulmonary and intestinal mucosal immune responses during infection with the helminth parasite Ascaris suum in pigs. A. suum infection induced a type 2-biased immune response in lung and intestinal tissues, characterized by pulmonary granulocytosis, increased Th2/Th1 T cell ratios in tracheal-bronchial lymph nodes, intestinal eosinophilia, and modulation of genes involved in mucosal barrier function and immunity. We observed that PAC had only minor effects on pulmonary immune responses, regardless of concurrent A. suum infection. However, RNA-sequencing of intestinal tissues revealed that dietary PAC significantly enhanced transcriptional responses related to immune function, antioxidant responses, and cellular stress activity, both in uninfected and A. suum-infected animals. A. suum infection and dietary PAC both induced distinct changes in gut microbiota composition, primarily in the jejunum and colon, respectively. Notably, PAC substantially increased Limosilactobacillus reuteri abundance in the colon of both naive and A. suum-infected animals. Thus, dietary PAC may have distinct beneficial effects on intestinal health during infection with mucosal pathogens, whilst having limited activity to modulate naturally-induced type-2 pulmonary inflammation. Our results shed further light on the mechanisms underlying the health-promoting properties of PAC-rich foods, and may aid in the design of novel dietary supplements to regulate mucosal inflammatory responses in the gastrointestinal tract.