Abstract
Plant extracts, or phytonutrients, are used in traditional medicine practices as supplements to enhance the immune system and gain resistance to various infectious diseases and are used in animal production as health promoting feed additives. To date, there are no studies that have assessed their mechanism of action and ability to alter mucosal immune responses in the intestine. We characterized the immunomodulatory function of six phytonutrients: anethol, carvacrol, cinnamaldehyde, eugenol, capsicum oleoresin and garlic extract. Mice were treated with each phytonutrient to assess changes to colonic gene expression and mucus production. All six phytonutrients showed variable changes in expression of innate immune genes in the colon. However only eugenol stimulated production of the inner mucus layer, a key mucosal barrier to microbes. The mechanism by which eugenol causes mucus layer thickening likely involves microbial stimulation as analysis of the intestinal microbiota composition showed eugenol treatment led to an increase in abundance of specific families within the Clostridiales order. Further, eugenol treatment confers colonization resistance to the enteric pathogen Citrobacter rodentium. These results suggest that eugenol acts to strengthen the mucosal barrier by increasing the thickness of the inner mucus layer, which protects against invading pathogens and disease.
Highlights
Phytonutrient diet supplementation promotes beneficial Clostridia species and intestinal mucus secretion resulting in protection against enteric infection
Eugenol treatment confers colonization resistance to the enteric pathogen Citrobacter rodentium. These results suggest that eugenol acts to strengthen the mucosal barrier by increasing the thickness of the inner mucus layer, which protects against invading pathogens and disease
Mucus production is an energy intensive process, and it is becoming clear that products of microbial metabolism, such as short-chain fatty acids (SCFAs), may provide the extra energy required for mucus generation in the intestine, as they can feed into the citric acid cycle
Summary
Phytonutrient diet supplementation promotes beneficial Clostridia species and intestinal mucus secretion resulting in protection against enteric infection. Phytonutrients, are used in traditional medicine practices as supplements to enhance the immune system and gain resistance to various infectious diseases and are used in animal production as health promoting feed additives. Eugenol treatment confers colonization resistance to the enteric pathogen Citrobacter rodentium These results suggest that eugenol acts to strengthen the mucosal barrier by increasing the thickness of the inner mucus layer, which protects against invading pathogens and disease. Butyrate production by microbes has been implicated in a feedback mechanism that is involved in upregulating mucus production by goblet cells in response to mucin utilization, replenishing the utilized mucins and associated glycans[25,26] Through this positive feedback loop, certain microbes may promote host-mediated mucus secretion through the utilization of mucins and their associated carbohydrates as an energy source. Mucus production is an energy intensive process, and it is becoming clear that products of microbial metabolism, such as SCFAs, may provide the extra energy required for mucus generation in the intestine, as they can feed into the citric acid cycle
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