Abstract
Accumulating evidence supports the crucial role intestinal microbiota and their metabolites play in the homeostasis of organisms. An important class of metabolites that have been shown to affect the immune system are short chain fatty acids (SCFAs). These SCFAs can affect the host cells via passive diffusion or via ligation to receptors, among others G-protein coupled receptor (GPR) 41 and 43. GPR41 and GPR43 are both part of a family of GPR40-related receptors. Mammalian studies have shown an important role for GPR41 and GPR43 in the modulation of immune responses by SCFAs. However, up till date, no validated coding sequences for orthologues of these SCFA receptors have been published for teleost fish. We used genomic resources and cDNA cloning, to identify and validate ten coding sequences for gpr40L genes in common carp. Phylogenetic analysis showed a division into three subclasses, putatively named class a, b and c, and showed the common carp genes had a closer phylogenetic relationship to mammalian GPR43 than to mammalian GPR41. Synteny analysis revealed a clear conservation of syntenic relationships between gpr40L in the genomes of spotted gar and common carp with the relevant region in the human genome. This conservation of synteny validates the genes identified, as gpr40L. Finally, presence of gpr40L genes was investigated in silico for genomes of 25 different, mostly teleost, fish species largely confirming the observations for gpr40L of common carp with regards to both, subdivision in three subclasses a-c and conservation of synteny. Our data provide an important first step towards an understanding of the role and function of receptors for SCFAs and immunomodulation in fish.
Highlights
Ever increasing evidence suggests that the microbiota of the gastrointestinal tract of mammals plays a pivotal role in the regulation of a wide range of biological processes with metabolic, endocrine and im mune functions [As reviewed by: (Butt and Volkoff, 2019; Rosenbaum et al, 2015; Wu and Wu, 2012)]
The critical roles of short-chain fatty acids (SCFAs) in the regulation of cellular function can be indirectly or directly exerted as SCFAs can be absorbed by passive diffusion into cells, a process greatly enhanced by different solute transporters and because SCFAs can act as ligands for G protein-coupled receptors (GPCRs), resulting in an active regulation via receptor activation [As reviewed by: (Parada Venegas et al, 2019; Yang et al, 2018)]
An initial BLAST search with human and mouse sequences for GPR41 and GPR43, identified ten GPR40-like sequences and a noncoding remnant of a gpr40L gene divided over four regions of the common carp genome
Summary
Ever increasing evidence suggests that the microbiota of the gastrointestinal tract of mammals plays a pivotal role in the regulation of a wide range of biological processes with metabolic, endocrine and im mune functions [As reviewed by: (Butt and Volkoff, 2019; Rosenbaum et al, 2015; Wu and Wu, 2012)]. Fermentation of dietary fibres and the resulting SCFA production explains at least part of the regulation of immune functions by dietary fibre supplementation, as SCFAs have been shown in mammals to have clear immunomodulatory effects on leukocyte recruitment, cytokine production, lymphocyte activation, phagocytosis or oxygen radical production [As reviewed by: (Vinolo et al, 2011)]. The presence of SCFAs can result in hyper-acetylation and facilitate the binding of transcription factors to promotor regions, leading to active gene transcription in a process called epigenetic reprogramming. When SCFAs are recognised by certain GPCRs, knowns as free fatty acid receptors (FFARs), a signalling cascade results in regulation of genes important for intestinal health, which can explain subsequent immunomodulatory effects of SCFAs [As reviewed by: (Rauf et al, 2021)]. Presence and activation of these re ceptors can be crucial for intestinal homeostasis and immune
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