Enteric defensins are essential regulators of intestinal microbial ecology

By Nita H. Salzman, Kuiechun Hung, Dipica Haribhai, Hiutung Chu, J. Karlsson-Sjöberg, Elad Amir, Paul Teggatz, Melissa Barman, Michael A. Hayward, D. Eastwood and 7 more. Nature Immunology, 2009

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Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell α-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if α-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human α-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse α-defensins. In these complementary models, we detected significant α-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to α-defensins in regulating the makeup of the commensal microbiota.

Subfields: Emergency Medical Services, Food Science, Microbiology

View Paper: https://www.semanticscholar.org/paper/637b9645a0cf13eeb7b4bf24a059575b2418723e

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Citations in the corpus

The microbiota of the respiratory tract: gatekeeper to respiratory health (2017, background): “Furthermore, in vitro activation of epithelial TLRs and nucleotide-binding oligomerization domain (NOD)-like receptors induced the release of antimicrobial peptides, such as β-defensin 2 (REF. 138 ), which could potentially influence the composition of the upper respiratory tract (URT) microbiota 16”
Mechanisms and consequences of intestinal dysbiosis (2017, background): “Crohn’s disease is associated with polymorphisms in the NOD2 gene [136, 137].”
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation (2012, background): “It has been shown that a-defensins secreted into the ileum lumen persist in a functional state throughout the entire gut 27 and that alterations in antimicrobial peptides can affect the ecology of the small and large bowel microbiota 28 .”
Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases (2010, neutral): “Median age years (range) 40y (18-68) 40y (19-69) 64y (25-89)”
The Microbiome in Infectious Disease and Inflammation (2012, positive): “Thus, α-defensin deficiency was associated with decreased Bacteroidetes and increased Firmicutes frequencies, whereas the transgenic expression of human defensin 5 (HD5) in mice led to the reverse shift (60).”
Host remodeling of the gut microbiome and metabolic changes during pregnancy. (2012, background): “…gut microbiota is shaped by environmental factors, such as diet (Wu et al., 2011), host genetics (Spor et al., 2011), and the immune system, which, in particular, can have profound effects on the composition of the gut microbiota (Salzman et al., 2010; Slack et al., 2009; Vijay-Kumar et al., 2010).”
The human gut microbiome: ecology and recent evolutionary changes. (2011, background): “Altered levels of the expression of α-defensins in transgenic animals have demonstrated their potential to alter the community composition of the lumenal microbiota, but not biomass levels (79).”