202 high degree of mucosal dysbiosis (90–100%) (P=1.69x10-6). The Ly6/PLAUR domain containing protein 8 (Lypd8) also functions as an antimicrobial peptide and has previously been shown to be capable of protecting the host from invading pathogenic flagellated bacteria.86 Another example is the positive association between S100A8, which encodes S100 calcium-binding protein A8 (also known as calgranulin A), and Lachnospiraceae, which showed a negative association in individuals with high dysbiosis (P=1.78x10-5). S100A8 has a wide variety of functions in regulating inflammatory processes and forms a heterodimer with S100A9, also known as calprotectin, which is used a as biomarker for inflammatory activity in IBD. Its known antimicrobial activity towards bacteria via chelation of zinc ions, which are essential for microbial growth, may therefore be disrupted in a dysbiotic environment.44 Similar to the two previous examples, the observed association between the expression of IL1RN (encoding for the interleukin-1 receptor antagonist protein) and Lachnospiraceae shifted from positive to negative (P=4.10x10-5), indicating that the natural protection against the proinflammatory effects of IL-1β, which associates with Lachnospiraceae abundance, may be lost in circumstances of high microbial dysbiosis. Similarly, expression of the CXCL17 gene encoding for a mucosal chemokine protein known to exert broad antimicrobial activity87 positively correlated with Lachnospiraceae abundance, which was clearly different among individuals with higher dysbiosis scores. Chapter 6
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