PMID- 34378979
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20220112
IS  - 2379-5042 (Electronic)
IS  - 2379-5042 (Linking)
VI  - 6
IP  - 4
DP  - 2021 Aug 25
TI  - Quantifying the Impact of Human Leukocyte Antigen on the Human Gut Microbiota.
PG  - e0047621
LID - 10.1128/mSphere.00476-21 [doi]
LID - e00476-21
AB  - The composition of the gut microbiota 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 those 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 microbiota. Here, we 
      investigated the effect of HLA haplotype on the microbiota composition. We 
      performed HLA typing and microbiota composition analyses on 3,002 public human 
      gut microbiome data sets. We found that individuals with functionally similar HLA 
      molecules are also similar in their microbiota composition. Our results show a 
      statistical association between host HLA haplotype and gut microbiota 
      composition. Because the HLA haplotype is a readily measurable parameter of the 
      human immune system, these results open the door to incorporating the genetics of 
      the immune system into predictive microbiome models. IMPORTANCE 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. The composition of the gut 
      microbiota varies among humans. Studies have proposed multiple factors driving 
      the observed variation, including diet, lifestyle, and health condition. Another 
      major influence on the microbiota is the host's genetic background. We 
      hypothesized the immune system to be one of the most important genetic factors 
      driving the differences observed between gut microbiotas. Therefore, we searched 
      for a link between the polymorphic molecules that shape human immune responses 
      and the composition of the microbiota. HLA molecules are the most polymorphic 
      molecules in our genome and therefore makes an excellent candidate to test such 
      an association. To our knowledge for the first time, our results indicate a 
      significant impact of the HLA on the human gut microbiota.
FAU - Andeweg, Stijn P
AU  - Andeweg SP
AD  - Theoretical Biology and Bioinformatics, Science for Life, Utrecht 
      Universitygrid.5477.1, Utrecht, the Netherlands.
FAU - Kesmir, Can
AU  - Kesmir C
AD  - Theoretical Biology and Bioinformatics, Science for Life, Utrecht 
      Universitygrid.5477.1, Utrecht, the Netherlands.
FAU - Dutilh, Bas E
AU  - Dutilh BE
AD  - Theoretical Biology and Bioinformatics, Science for Life, Utrecht 
      Universitygrid.5477.1, Utrecht, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210811
PL  - United States
TA  - mSphere
JT  - mSphere
JID - 101674533
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adaptive Immunity
MH  - Databases, Genetic
MH  - Datasets as Topic
MH  - Gastrointestinal Microbiome/*genetics/*immunology/physiology
MH  - Gene Expression Profiling
MH  - HLA Antigens/classification/*genetics/immunology
MH  - Haplotypes
MH  - Histocompatibility Testing
MH  - Humans
MH  - Symbiosis
MH  - T-Lymphocytes/immunology
MH  - Transcriptome
PMC - PMC8386457
OTO - NOTNLM
OT  - gut microbiome
OT  - human leukocyte antigen
OT  - immune-microbiome interactions
OT  - quantitative biology
EDAT- 2021/08/12 06:00
MHDA- 2022/01/13 06:00
PMCR- 2021/08/11
CRDT- 2021/08/11 12:12
PHST- 2021/08/12 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/08/11 12:12 [entrez]
PHST- 2021/08/11 00:00 [pmc-release]
AID - mSphere00476-21 [pii]
AID - 10.1128/mSphere.00476-21 [doi]
PST - ppublish
SO  - mSphere. 2021 Aug 25;6(4):e0047621. doi: 10.1128/mSphere.00476-21. Epub 2021 Aug 
      11.