Abstract
The microbiota regulates immunological development during early human life, with long-term effects on health and disease. Microbial products include short-chain fatty acids (SCFAs), formyl peptides (FPs), polysaccharide A (PSA), polyamines (PAs), sphingolipids (SLPs) and aryl hydrocarbon receptor (AhR) ligands. Anti-inflammatory SCFAs are produced by Actinobacteria, Bacteroidetes, Firmicutes, Spirochaetes and Verrucomicrobia by undigested-carbohydrate fermentation. Thus, fiber amount and type determine their occurrence. FPs bind receptors from the pattern recognition family, those from commensal bacteria induce a different response than those from pathogens. PSA is a capsular polysaccharide from B. fragilis stimulating immunoregulatory protein expression, promoting IL-2, STAT1 and STAT4 gene expression, affecting cytokine production and response modulation. PAs interact with neonatal immunity, contribute to gut maturation, modulate the gut–brain axis and regulate host immunity. SLPs are composed of a sphingoid attached to a fatty acid. Prokaryotic SLPs are mostly found in anaerobes. SLPs are involved in proliferation, apoptosis and immune regulation as signaling molecules. The AhR is a transcription factor regulating development, reproduction and metabolism. AhR binds many ligands due to its promiscuous binding site. It participates in immune tolerance, involving lymphocytes and antigen-presenting cells during early development in exposed humans.
Highlights
Introduction published maps and institutional affilThe human microbiota molds the immune system during early life, resulting in longterm consequences [1]
formyl peptides (FPs) induce neonatal neutrophil migration but inhibit reactive oxygen species (ROS) production mediated by phorbol myristate acetate, suggesting a mechanism that limits the detrimental effects of uncontrolled inflammation in neonates [202,203]
The role of SLPs on modulating the immune system was demonstrated by neonatal exposure of germ-free mice to glucosylceramide produced by B. fragilis, which diminishes the proliferation of invariant natural killer T cells during the postnatal period [234]
Summary
Perhaps the best-known intermediaries between the microbiota and their host are the short-chain fatty acids (SCFAs) derived from microbiota metabolism. SCFAs are produced by the Actinobacteria, Bacteroidetes, Firmicutes, Spirochaetes and Verrucomicrobia phyla. These include the Coprococcus, Roseburia [30,31,32], Akkermansia [33], Eubacterium, Faecalibacterium, Ruminococcus [34], Bacteroides, Propionibacteria [35], Eubacterium and Clostridium genera [36]. Depending on the amount of dietary fiber, the total SCFA concentration in the pig caecum can be as high as 164 mmol/kg contents [41]. Total SCFA levels in the caecum may reach the millimolar range [42] (Table 1). Reaches such distant sites as the brain [45]
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