Quantifying the Impact of Human Leukocyte Antigen on the Human Gut Microbiota

Abstract

The microorganisms that live in the digestive tracts of humans, known as the gut microbiota, are essential for hosts’ survival, as they support crucial functions. For example, they support the host in facilitating the uptake of nutrients and give colonization resistance against pathogens.

Host gene effects on gut microbiota in type 1 diabetes

“…Meanwhile, a recent study quantifying Il-10 deficiency in BDC2.5 + NOD mice increased susceptibility to islet autoimmunity through modulating neutrophil hemostasis, an effect accompanied by altered intestinal immunity and gut microbiome profile. [29] the influence of HLA alleles on human gut microbiota reported that individuals with similar HLA genes have similar microbiota profiles [42]. A correlation between variants located in the HLA region and gut microbiome composition was also found in a mGWAS study [47].…”

“…Subsequently, an accumulating body of research on transgenic and congenic mice indicated that MHC genetics contributes to shaping the gut microbiome, influencing the genesis and development of diseases [ 32 , 44 , 46 ]. Meanwhile, a recent study quantifying the influence of HLA alleles on human gut microbiota reported that individuals with similar HLA genes have similar microbiota profiles [ 42 ]. A correlation between variants located in the HLA region and gut microbiome composition was also found in a mGWAS study [ 47 ].…”

“…A correlation between variants located in the HLA region and gut microbiome composition was also found in a mGWAS study [ 47 ]. Furthermore, a population-based study of 3002 subjects showed that individuals with functionally similar HLA haplotypes are more likely to harbor similar microbiome profiles [ 42 ]. As for autoimmune T1D, the All Babies in Southeast Sweden (ABIS) prospective cohort study demonstrated that HLA genetic risk for developing autoimmune T1D is associated with microbiota variance in the gut [ 48 ].…”

“…Available evidence shows that the primary mechanism by which MHC II regulates host-microbiota interactions is by regulating T cell-dependent anti-commensal IgA responses [34,[36][37][38][39][40][41]. In turn, recent findings have suggested that MHC alleles are also associated with the diversification of the gut microbiome [42,43]. For instance, functional microbiome diversification among MHC congenic mouse strains was detected upon comparison of bacterial cellular fatty acid (CFA) profiles [44].…”

Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes

“…Similarly, regional differences in commensal microbiota composition may be considered a distinct category of environmental-driven endotype. However, mutual regulation and feedbacks make it difficult to draw a clear line between genetics- and environment-driven endotypes as HLA differences have been reported to influence the gut microbiome ( 193 ). A recent report indicated that individuals carrying at-risk HLA haplotypes seem to have a distinct core microbiome and beta diversity compared to the general population ( 194 ).…”