Effects of dietary fiber components and gut microbiota products on the immune system: a focus on grape pomace as a novel source of fermentable substrates and bioactives

Diet-microbiota-host interactions influence host immune function and metabolic activities, affecting health and disease states. Three studies examined the immune impact of microbiota, diet, host-derived metabolites and dietary interventions, utilizing in vivo and in vitro approaches. Immunomodulatory activity of the Lacticaseibacillus rhamnosus R0011 secretome in combination with retinoic acid was examined using a human antigen-presenting cell (APC) model. These metabolites drove APC differentiation into a tolerogenic dendritic-like cell phenotype, providing insight into gut microbiota-host interactions. Polyphenol bioactives are dietary-derived metabolites. Immunomodulatory and antioxidant mechanistic behaviour of phenolics extracted from grape pomace (GP), a novel source of dietary fiber (DF), were investigated using human and rat intestinal epithelial cell (IEC) and APC lines. GP phenolic extract (GPE) demonstrated immunomodulatory and antioxidant activity, attenuating proinflammatory cascades and reducing oxidative stress in APC and IEC. GPE decreased proinflammatory chemokine production (CINC-1 and CINC-α/β) in tumour necrosis factor-α (TNF-α) challenged IEC-6 cells, and oxidative stressor-induced reactive oxygen species and nitrogen reactive species levels in IEC-6 IECs and NR8383 APCs. In co-cultures, GPE pre-conditioned IEC-6 IECs downregulated LPS-induced TNF-α production by NR8383 APCs. Phosphoflow cytometry analyses revealed that GPE down-regulated key signaling molecules in the NF-κB and mitogen-activated protein kinase signaling pathways. A trial using Wistar rats fed high-fat high-sugar (HFHS) diets investigated impacts of GP consumption on immune and metabolic activities and potential sex-based differences in diet impact. In male rats, adiponectin levels were enhanced by GP supplementation relative to the control HFHS diet. GP supplementation decreased proinflammatory IL-1β cytokine levels in Peyer’s patches (PP) of female rats compared to males. In the liver, female rats on the HFHS+GP diet had higher IL-10 and CRP levels than on the HFHS+fructooligosaccharide (FOS) diet, and higher IFN-γ levels than on the HFHS+wheat bran (WB) diet, while males had lower IL-4 levels on the HFHS+GP diet than on the HFHS-control diet, indicating differences between sexes in the impact of these diets at a systemic location. Altogether, these findings provide novel insights into complex interactions in the gut, impact on proinflammatory and regulatory immune activity, and effects of dietary interventions and sex-based differences on immune, metabolic and physiological outcomes.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Discipline thesis:degree_discipline

Applied Bioscience

Grantor

University of Ontario Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Saleem, Lin

Advisors dc:contributor.advisor

• Green-Johnson, Julia
• Clarke, Sandra

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10155/2079

OAI identifier oai:identifier

oai:ontariotechu.scholaris.ca:10155/2079