A ntimicrobial peptides and gut microbiota in homeostasis and pathology

Abstract

We survive because we adapted to a world of microorganisms. All our epithelial surfaces participate in keeping up an effective barrier against microbes while not initiating ongoing inflammatory processes and risking collateral damage to the host. Major players in this scenario are antimicrobial peptides (AMPs). Such broad-spectrum innate antibiotics are in part produced by specialized cells but also widely sourced from all epithelia as well as circulating inflammatory cells. AMPs belong to an ancient defense system found in all organisms and participated in a preservative co-evolution with a complex microbiome. Particularly interesting interactions between host barrier and microbiota can be found in the gut. The intestinal cell lining not only has to maintain a tightly regulated homeostasis during its high-throughput regeneration, but also a balanced relationship towards an extreme number of mutualistic or commensal inhabitants. Recent research suggests that advancing our understanding of the circumstances of such balanced and sometimes imbalanced interactions between gut microbiota and host AMPs should have therapeutic implications for different intestinal disorders.

Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats

“…This physical barrier consists of enterocytes tightly connected by intracellular junctions [43]. Depending on the level of injury, enterocytes also secrete cytokines and chemokines, which trigger the inflammatory response, as a second line of defense against the luminal contents [7,44,45], resulting in infiltration of neutrophils, macrophages and other immune cells to the site of intestinal damage or inflammation [4]. …”

Pathophysiological Role of TNF in Inflammatory Bowel Disease: TNF and Its Impact on Barrier Function

“…However, recent work has instead suggested that defensins interact with Lipid II and thereby interrupt bacterial cell wall synthesis [15] . Depending on their intramolecular disulfide bonding pattern, defensins present in the gut are subdivided into α-and β-defensins [16] . Of the six α-defensins identified in Paneth cells so far, human defensin-5 (HD5) and human defensin-6 (HD6) are of particular importance for the small intestinal immune system.…”

The Development of Our Organ of Other Kinds—The Gut Microbiota

“…For example, specialized Paneth cells in the small intestine store and secrete various antimicrobial effectors (e.g., lysozyme, phospholipase A2 group IIA or REGIII); but their most abundant products are the α-defensins human defensin (HD) 5 and HD6. Both α-defensins and β-defensins are bactericidal, with activity against Gram-negative and Gram-positive bacteria (Bevins and Salzman, 2011; Ostaff et al, 2013). It was reported that human gut microbes from all dominant phyla are resistant to high levels of Cationic AMPs polymyxin B.…”