[6] Paneth cells secrete antimicrobial peptides and proteins, which are "key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens.

[9] Paneth cells are stimulated to secrete defensins when exposed to bacteria (both Gram positive and Gram-negative types), or such bacterial products as lipopolysaccharide, lipoteichoic acid, muramyl dipeptide and lipid A.

[5] The antimicrobial activity of HD-6 consists of self-assembling into extracellular nets that entrap bacteria in the intestine and thereby preventing their translocation across the epithelial barrier.

[16] Human Paneth cells also produce other AMPs including lysozyme, secretory phospholipase A2, and regenerating islet-derived protein IIIA.

[10] This battery of secretory molecules gives Paneth cells a potent arsenal against a broad spectrum of agents, including bacteria, fungi and even some enveloped viruses.

The phagocytic function of Paneth cells was discovered using a series of experiments, one of which made use of mice that were radiated with a low dose Cesium-137 (137Cs), mimicking chemotherapy undergone by cancer patients.

Mice lacking the (ZnT)2 transporter not only exhibit impaired granule secretion, they also suffer from increased inflammatory response to lipopolysaccharide and are less capable of bactericidal activity.

It has been speculated that the storage of heavy metals contributes to direct antimicrobial toxicity, as Zn is released upon cholinergic PC stimulation.

[25] Abnormal Paneth cells with reduced expression or secretion of defensins HD-5 and HD-6 (in human) and antimicrobial peptides are associated with inflammatory bowel disease.

[26][17] In addition to that, several of the Crohn's disease-risk alleles are associated with Paneth cell dysfunction are involved in processes such as autophagy, the unfolded protein response, and the regulation of mitochondrial function.

[17] It is believed that the dysfunction of Paneth cells compromises antimicrobial peptides leading to a microbiota composition shift, and even dysbiosis.

[28] Collectively, these findings support the theory that Paneth cell dysfunction may lead to a dysbiotic microbiota that, in turn, could predispose an individual to the development of Crohn's disease.

[30] The mechanism that links Paneth cells to necrotizing enterocolitis remains unclear, but it has been theorized that a bloom of Proteobacteria and, more specifically, Enterobacteriaceae species precedes the development of the condition.

[33] and at least one murine model suggests that when α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration, liver fibrosis is ameliorated as a result of the dysbiosis resolving.

[34] One study described the injection of dithizone, which can disrupt cell granulates, into mice that were fed a high-fat diet in order to identify Paneth-cell-oriented microbial alterations.

The application of dithizone improved high-fat diet glucose intolerance and insulin resistance and was associated with an alleviation in the severity of liver steatosis in HFD mice, possibly through gut microbiome modulation involving the increase in Bacteroides.