Table 4.

The impact of diet on PCs and gastrointestinal function.

Diet	Effect on Paneth cells	Outcome of the diet	Factors reinforcing the effect of the diet on Paneth cells	References
Alcohol	Reduced expression of antimicrobial peptides (α‐defensins) Decreased density and size of Paneth cell granules	Increased bacterial translocation towards the liver Reduced antimicrobial activity of crypts Dysbiosis Outcome reversed by synthetic HD5 Treatment	MMP7 KO mice (α‐defensin‐deficient mice) Zinc deficiency	Purohit et al (2008), Zhong et al (2020)
Western diet	Paneth cell dysfunction	Reduced intestinal barrier function Dysbiosis		Liu et al (2021)
High‐fat diet	Reduced expression of antimicrobial peptides (α‐defensins and RegIIIγ) Increased Paneth cell death	Impaired intestinal barrier function Dysbiosis	Vitamin D receptor KO mice	Su et al (2016), Guo et al (2017), Lee et al (2017)
Oxidized n‐3 polyunsaturated fatty acids (n3‐PUFA)	Decreased Paneth cell numbers in the duodenum compared to unoxidized n3‐PUFA	Oxidative stress and inflammation in the upper intestine		Awada et al (2012)
Arginine supplementation	Increased expression and secretion of AMPs	Boost of innate immune response in the small intestine		Ren et al (2014)
Ketogenic diet	Increased Paneth cell numbers and activity	Stimulates differentiation in the small intestine via 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2)/and the ketone body β‐hydroxybutyrate (βHB)		Wang et al (2017b)
Caloric restriction	Decreased mTORC1 activity in Paneth cells	Paneth cell produced cyclic ADP ribose promotes self‐renewal of intestinal stem cells		Yilmaz et al (2012)
Starvation	Decreased expression and secretion of antimicrobial peptides (α‐defensins, Lysozyme and RegIIIγ) Aberrant granule formation Increased autophagy	Increased intestinal permeability Increased bacterial translocation towards mesenteric lymph nodes		Hodin et al (2011a)