TY - JOUR

T1 - The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection

AU - Zhu, Ling

AU - Andersen-Civil, Audrey I.S.

AU - Myhill, Laura J.

AU - Thamsborg, Stig M.

AU - Kot, Witold

AU - Krych, Lukasz

AU - Nielsen, Dennis S.

AU - Blanchard, Alexandra

AU - Williams, Andrew R.

N1 - Funding Information: This work was supported by the Lundbeck Foundation ( R252-2017-1731 ) and Independent Research Fund Denmark ( 7026-0094B ). LZ was supported by the China Scholarship Council (Grant 201806910065 ). The funding bodies had no involvement in study design, data acquisition or decision to publish. Publisher Copyright: © 2021

PY - 2022

Y1 - 2022

N2 - Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

AB - Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

KW - Cinnamaldehyde

KW - Inflammation

KW - Microbiota

KW - Parasite

U2 - 10.1016/j.jnutbio.2021.108887

DO - 10.1016/j.jnutbio.2021.108887

M3 - Journal article

C2 - 34655757

AN - SCOPUS:85119268238

VL - 100

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

SN - 0955-2863

M1 - 108887

ER -