Objective: The gut microbiome is affected by a number of factors, including the innate and adaptive immune system. The major histocompatibility complex (MHC), or the human leukocyte antigen (HLA) in humans, performs an essential role in vertebrate immunity, and is very polymorphic in different populations. HLA determines the specificity of T lymphocyte and natural killer (NK) cell responses, including against the commensal bacteria present in the human gut. Thus, it is likely that our HLA molecules and thereby the adaptive immune response, can shape the composition of our microbiome. Here, we investigated the effect of HLA haplotype on the microbiome composition. Results: We performed HLA typing and microbiota composition analyses on 3,002 public human gut microbiome datasets. We found that (i) individuals with functionally similar HLA molecules (i.e. presenting similar peptides) are also similar in their microbiota, and (ii) HLA homozygosity correlated with microbiome diversity, suggesting that diverse immune responses limit microbiome diversity. Conclusion: Our results show a statistical association between host HLA haplotype and gut microbiome composition. Because the HLA haplotype is a readily measurable parameter of the human immune system, these results open the door to incorporating the immune system into predictive microbiome models.
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