Polymorphic Immune Mechanisms Regulate Commensal Repertoire

Khan, Aly A.; Yurkovetskiy, Leonid; O'Grady, Kelly; Pickard, Joseph M.; Pooter, Renée de; Antonopoulos, Dionysios A.; Golovkina, Tatyana V.; Chervonsky, Alexander V.

doi:10.1016/j.celrep.2019.09.010

Cited by 68 publications

(81 citation statements)

References 60 publications

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“…Above, we presented the first statistical evidence in humans that HLA significantly affects the composition of the gut microbiota, in line with previous results in other animals (Khan et al, 2019; Kubinak et al, 2015; Mao et al, 2018). We expect that the immune system may be one of the most important genetic factors influencing the microbiome (Bonder et al, 2016; Goodrich et al, 2014).…”

Section: Resultssupporting

confidence: 90%

“…These factors include dietary components, mode of delivery during birth, breastfeeding, disease history, and host genetics (Belkaid & Hand, 2014; Bonder et al, 2016; Goodrich et al, 2016, 2014; Kolde et al, 2018). Studies with monozygotic twins have highlighted the importance of host genetics in shaping the microbiome (Reyes et al, 2010; Zhou et al, 2016), where the immune system is thought to be one of the most important contributing factors (Khan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Together these molecules form the first essential step in the generation of an adaptive immune response. Influence of the MHC haplotype on the microbiome has been observed in mice (Khan et al, 2019; Kubinak et al, 2015; Lin et al, 2014; Toivanen et al, 2001) and in stickleback (Bolnick et al, 2014). In humans, specific polymorphisms in the HLA region have been associated to several common infections (Tian et al, 2017) and in a recent genome-wide association study of over 1,500 individuals two out of the nine genetic variants associated to the microbiome composition were within the HLA region (Bonder et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

Andeweg

Keşmir

Dutilh

2020

Preprint

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11Objective: The gut microbiome is affected by a number of factors, including the innate and adaptive 12 immune system. The major histocompatibility complex (MHC), or the human leukocyte antigen 13 (HLA) in humans, performs an essential role in vertebrate immunity, and is very polymorphic in 14 different populations. HLA determines the specificity of T lymphocyte and natural killer (NK) cell 15 responses, including against the commensal bacteria present in the human gut. Thus, it is likely that 16our HLA molecules and thereby the adaptive immune response, can shape the composition of our 17 microbiome. Here, we investigated the effect of HLA haplotype on the microbiome composition. 18Results: We performed HLA typing and microbiota composition analyses on 3,002 public human gut 19 microbiome datasets. We found that (i) individuals with functionally similar HLA molecules (i.e. 20presenting similar peptides) are also similar in their microbiota, and (ii) HLA homozygosity correlated 21 with microbiome diversity, suggesting that diverse immune responses limit microbiome diversity. 22Conclusion: Our results show a statistical association between host HLA haplotype and gut 23 microbiome composition. Because the HLA haplotype is a readily measurable parameter of the 24 human immune system, these results open the door to incorporating the immune system into 25 predictive microbiome models. 26 27 IMPORTANCE The microorganisms that live in the digestive tracts of humans, known as the gut 28 microbiome, are essential for hosts survival as they support crucial functions. For example, they 29 support the host in facilitating the uptake of nutrients and give colonization resistance against 30 pathogens. The composition of the gut microbiome varies among humans. Studies have proposed 31 multiple factors driving the observed variation, including; diet, lifestyle, and health condition. 32Another major influence on the microbiome is the host's genetic background. We hypothesized the 33 immune system to be one of the most important genetic factors driving the differences observed 34 between gut microbiomes. Therefore, we are interested in linking the polymorphic molecules that 35 play a role in human immune responses to the composition of the microbiome. HLA molecules are 36 the most polymorphic molecules in our genome and therefore makes an excellent candidate to test 37 such an association/link. To our knowledge for the first time, our results indicate a significant impact 38 of the HLA on the human gut microbiome composition. 39 40 365 Ando, H., Mizuki, N., Ota, M., Yamazaki, M., Ohno, S., Goto, K., … Inoko, H. (1997). Allelic variants of the human MHC class I 366 chain-related B gene (MICB). Immunogenetics, 46(6), 499-508. https://doi.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

Andeweg

Keşmir

Dutilh

2020

Preprint

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“…Although far to be fully understood, some examples of host-genetic microbiota associations have been reported (reviewed in ), that similar to our results identify candidate genes mainly related to host-response against pathogens, sensing microbes, cell signaling pathways and innate immune system. However, in agreement with previous reports (Khan et al 2019;Rothschild et al 2018), ours findings also indicate a limited and target specific host genetic control over the composition of the gut eukaryote communities in pig.…”

Section: Discussionsupporting

confidence: 93%

“…Colonization with this species has not been associated to virulence in mammals, but the full pathogenic potential of T. batrachorum has yet to be explored. These findings are in line with recent reports in mice (Khan et al 2019), and suggest that polymorphisms located in (or in linkage disequilibrium with) genes related to immune system and gut homeostasis may modulate the diversity and composition of the eukaryote gut communities in pigs. The evolutionary mechanism beyond the observed association may be explained by indirect relationships between mutual favorable selection at host-genome and microbial level Zilber-Rosenberg and Rosenberg 2008).…”

Section: Discussionsupporting

confidence: 92%

Gut eukaryotic communities in pigs: diversity, composition and host genetics contribution

Ramayo-Caldas

Prenafeta²,

Zingaretti

et al. 2020

Preprint

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AbstractThis study aims to characterize commensal fungi and protists inhabiting the gut of healthy pigs, and explore the putative host genetic control over diversity and composition of pig gut eukaryotes. Fecal fungi and protists communities from 514 Duroc pigs of two sexes and two different ages were characterized by 18S and ITS ribosomal RNA gene sequencing. The gut mycobiota was dominated by yeasts, with a high prevalence of Kazachstania spp. Regarding protists, representatives of four genera (Blastocystis, Neobalantidium, Tetratrichomonas and Trichomitus) persisted through more than the 80% of the pigs. Heritabilities for the diversity and abundance of gut eukaryotic communities were estimated with the subset of 60 days aged piglets (N=405). Obtained heritabilities ranged from 0.15 to 0.28, indicating a rather limited host-genetic control. A genome wide association study reported genetic variants associated with the fungal α-diversity (SSC6) and with the abundance of Blastocystis spp. (SSC6, SSC17 and SSC18). Annotated candidate genes (IL23R, IL12RB2, PIK3C3, PIK3CD, HNF4A and TNFRSF9) were mainly related to immunity, gut homeostasis and metabolic processes. Our results point towards a minor and taxa specific genetic control over the diversity and composition of the pig gut eukaryotic communities.

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Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice

Zhong

Lee

et al. 2021

Arch Toxicol

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Polymorphic Immune Mechanisms Regulate Commensal Repertoire

Cited by 68 publications

References 60 publications

Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

Gut eukaryotic communities in pigs: diversity, composition and host genetics contribution

Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice

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