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The human gastrointestinal tract has many barriers that prevent colonisation by pathogenic microorganisms.1 Cationic antimicrobial peptides produced by intestinal epithelial cells contribute to defence against bacterial infections.2 Human defensin 5 (HD-5) is the most abundant cationic antimicrobial peptide secreted by Paneth cells in the small intestine and plays a crucial role in the innate immune system.3 HD-5 exhibits broad-spectrum antimicrobial activity by piercing the bacterial membrane, thereby killing bacteria.4
In Gut, Li et al have designed an HD-5-based small peptide named D3.5 It is constituted by the modification of the first 9-aa at the N-terminus of HD-5, one of the fragments that is degraded by proteases in the human duodenal fluid. This modification confers D3 the ability to penetrate cell membranes and to be taken up by the intestine on oral delivery. Daily intragastric administration of D3 in high-fat diet fed mice lowered weight gain and adiposity, improved glucose tolerance, enhanced insulin sensitivity and restored leptin sensitivity. All these beneficial metabolic effects were attributed to the reduced food intake, while other metabolic parameters such as energy expenditure remained unaltered. D3 seemed to specifically act in the intestine, particularly in the distal small intestine, where the fluorescent labelled peptide was visualised. A transcriptome analysis …
Contributors Both authors have written this commentary.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.