Shotgun Metagenomics of 250 Adult Twins Reveals Genetic and Environmental Impacts on the Gut Microbiome

Xie, Hailiang; Guo, Ruijin; Huang, Zhong; Feng, Qiang; Lan, Zhou; Qin, Bingcai; Ward, Kirsten; Jackson, Matthew A.; Xia, Yan; Xu, Chen; Chen, Bing; Xia, Huihua; Xu, Changlu; Li, Fēi; Xu, Xun; Al‐Aama, Jumana Y.; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Wang, Jun; Steves, Claire J.; Bell, Jordana T.; Li, Junhua; Spector, Timothy D.; Jia, Huijue

doi:10.1016/j.cels.2016.10.004

Cited by 264 publications

(280 citation statements)

References 87 publications

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“…In some cases, siblings had (nonsignificantly) higher rmSNV similarity than twins, which is likely due to chance. Overall, the results are in line with a recent study on adult twins in which monozygotic twins did not share more strains than dizygotic twins, indicating a lack of genetic influence on strain sharing (Xie et al 2016;Rothschild et al 2017).…”

Section: Strain Transmission Between Family Members In Adulthoodsupporting

confidence: 90%

“…While the species composition of gut microbiota has been reported to be influenced by host genetics (Xie et al 2016), our results demonstrate that the identity of the strains within a species is dependent on the environment (Rothschild et al 2017). Family members are likely the most important environmental source of human gut microbes, and bacterial transmission between family members occurs also in later stages of life.…”

Section: Discussionmentioning

confidence: 61%

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Selective maternal seeding and environment shape the human gut microbiome

et al. 2018

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Vertical transmission of bacteria from mother to infant at birth is postulated to initiate a life-long host-microbe symbiosis, playing an important role in early infant development. However, only the tracking of strictly defined unique microbial strains can clarify where the intestinal bacteria come from, how long the initial colonizers persist, and whether colonization by other strains from the environment can replace existing ones. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Only strains from the classes Actinobacteria and Bacteroidia, which are essential components of the infant microbiome, are transmitted from the mother and persist for at least 1 yr. In contrast, maternal strains of Clostridia, a dominant class in the mother's gut microbiome, are not observed in the infant. Caesarean-born infants show a striking lack of maternal transmission at birth. After the first year, strain influx from the family environment occurs and continues even in adulthood. Fathers appear to be more frequently donors of novel strains to other family members than receivers. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time.

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Section: Strain Transmission Between Family Members In Adulthoodsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 61%

Selective maternal seeding and environment shape the human gut microbiome

et al. 2018

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“…Interestingly, Blekhman et al observed an enrichment of microbiome associated genes in the Primary Bile Acid Biosynthesis KEGG pathway (4). In addition, Xie et al reported that the abundance of bile salt hydrolase genes was significantly heritable in UK Twins (Heritability = 0.29) (69), and Bonder et al identified an association between the MetaCyc bacterial bile acid metabolism pathway and SNPs in the ARAP2 gene (5). All of these studies support an interaction between host genetics and the microbiome through regulation of bile acid metabolism.…”

Section: Gwas Reveal Tissues Pathways and Genes Consistently Associmentioning

confidence: 99%

The Relationship Between the Human Genome and Microbiome Comes into View

et al. 2017

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The microbiome’s involvement in health and disease, and the complexity of its composition and function, make it intriguing to consider human genetic factors that impact microbiome composition. Genes may influence health through their ability to promote a stable microbial community in the gut. Studies of heritability yield a consistent subset of microbes that are impacted by genes, but the use of genome-wide association studies (GWAS) to identify specific genetic variants associated with microbiota phenotypes has proven challenging. Processing microbiome datasets into traits to be modeled and reducing the burden of multiple testing are just some of the technical hurdles in microbiome GWAS. Studies to date are small by GWAS standards, making cross-study comparisons and validations particularly important in identifying authentic signals. Cross-study comparisons are hampered by differences in analytical approaches. Nevertheless, some consistent associations have emerged between populations, most notably between Bifidobacteria and the lactase non-persister genotype. These early successes open the way for the microbiome to be incorporated into studies that quantify interactions among genotype, environment, and the microbiome for predicting disease susceptibility.

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“…However, twin studies can tease these factors apart by comparing microbiome similarity among monozygotic (MZ) and dizygotic (DZ) twins, under the assumption that significant differences in the degree of similarity are attributed solely to genetic effects. Recent twin studies have demonstrated that the level of similarity is almost the same for MZ and DZ twins [24], that both MZ and DZ twins have extremely similar gut microbiomes compared with non-twin pairs [24], and that this similarity decreases when twins start living apart [32]. These results indicate that environment overshadows host genetics in shaping the gut microbiome.…”

Section: The Microbiome Is Predominantly Shaped By Non-genetic Factorsmentioning

confidence: 97%

“…Recent studies employing these technologies have uncovered evidence for both environmental and host genetic association with the microbiome composition [8,11,20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. However, to date there is no consensus regarding how and to what extent does host genetics shapes the gut microbiome, as compared to environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Host genetics and microbiome associations from the lens of genome wide association studies

Weissbrod

Rothschild

Barkan

et al. 2018

Preprint

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Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome-host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome-host genotypes associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: (a) Adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; (b) enforcing stringent statistical criteria to reduce the number of false positive findings; and (c) considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.26615v1 | CC BY 4.0 Open Access | rec: 5

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Shotgun Metagenomics of 250 Adult Twins Reveals Genetic and Environmental Impacts on the Gut Microbiome

Cited by 264 publications

References 87 publications

Selective maternal seeding and environment shape the human gut microbiome

Selective maternal seeding and environment shape the human gut microbiome

The Relationship Between the Human Genome and Microbiome Comes into View

Host genetics and microbiome associations from the lens of genome wide association studies

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