• Valdes, A. M., Walter, J., Segal, E. & Spector, T. D. Role of the gut microbiota in nutrition and health. BMJ 361, k2179 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tarracchini, C. et al. Exploring the vitamin biosynthesis landscape of the human gut microbiota. mSystems 9, e0092924 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • de Vos, W. M., Tilg, H., Van Hul, M. & Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 71, 1020–1032 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Geng, J., Ni, Q., Sun, W., Li, L. & Feng, X. The links between gut microbiota and obesity and obesity related diseases. Biomed. Pharmacother. 147, 112678 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Van Hul, M. & Cani, P. D. The gut microbiota in obesity and weight management: microbes as friends or foe? Nat. Rev. Endocrinol. 19, 258–271 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Kandalai, S., Li, H., Zhang, N., Peng, H. & Zheng, Q. The human microbiome and cancer: a diagnostic and therapeutic perspective. Cancer Biol. Ther. 24, 2240084 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vivarelli, S. et al. Gut microbiota and cancer: from pathogenesis to therapy. Cancers 11, 38 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vich Vila, A. et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 11, 362 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Amato, K. R. et al. The human gut microbiome and health inequities. Proc. Natl Acad. Sci. USA 118, e2017947118 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leeming, E. R., Johnson, A. J., Spector, T. D. & Le Roy, C. I. Effect of diet on the gut microbiota: rethinking intervention duration. Nutrients 11, 2862 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schmidt, T. S. B., Raes, J. & Bork, P. The human gut microbiome: from association to modulation. Cell 172, 1198–1215 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Benson, A. K. et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc. Natl Acad. Sci. USA 107, 18933–18938 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014). This important early study uses data from twins to estimate gut microbiome heritability.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Visscher, P. M., Hill, W. G. & Wray, N. R. Heritability in the genomics era—concepts and misconceptions. Nat. Rev. Genet. 9, 255–266 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19, 731–743 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davenport, E. R. et al. Genome-wide association studies of the human gut microbiota. PLoS One 10, e0140301 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • O’Callaghan, A. & van Sinderen, D. Bifidobacteria and their role as members of the human gut microbiota. Front. Microbiol. 7, 925 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Samuel, B. S. et al. Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut. Proc. Natl Acad. Sci. USA 104, 10643–10648 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ignatyeva, O. et al. Christensenella minuta, a new candidate next-generation probiotic: current evidence and future trajectories. Front. Microbiol. 14, 1241259 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Rothschild D et al. Environment dominates over host genetics in shaping human gut microbiota. Yearb. Pediatr. Endocrinol. https://doi.org/10.1530/ey.15.14.5 (2018). This key study argues that microbiome heritability is low and that environment is stronger than genetics in shaping the gut microbiome.

  • Hughes, D. A. et al. Genome-wide associations of human gut microbiome variation and implications for causal inference analyses. Nat. Microbiol. 5, 1079–1087 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, J. et al. Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative. Microbiome 6, 101 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boulund, U. et al. Gut microbiome associations with host genotype vary across ethnicities and potentially influence cardiometabolic traits. Cell. Host. Microbe 30, 1464–1480.e6 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Gacesa, R. et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature 604, 732–739 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Zhernakova, D. V. et al. Host genetic regulation of human gut microbial structural variation. Nature 625, 813–821 (2024). This study investigates the heritability of structural variation in the gut microbiome.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Beaumont, M. et al. Heritable components of the human fecal microbiome are associated with visceral fat. Genome Biol. 17, 189 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Blekhman, R. et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 16, 191 (2015). This important early study demonstrates the feasibility of testing for genome-wide host genetic associations with gut microbiome measurements as quantitative traits.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grieneisen, L. et al. Gut microbiome heritability is nearly universal but environmentally contingent. Science 373, 181–186 (2021). This article describes a large study of microbiome heritability in wild primates.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hejazi, J., Amiri, R., Nozarian, S., Tavasolian, R. & Rahimlou, M. Genetic determinants of food preferences: a systematic review of observational studies. BMC Nutr. 10, 24 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vandeputte, D. et al. Temporal variability in quantitative human gut microbiome profiles and implications for clinical research. Nat. Commun. 12, 6740 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Org, E. et al. Genetic and environmental control of host–gut microbiota interactions. Genome Res. 25, 1558–1569 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, C. et al. Contribution of host genetics to the variation of microbial composition of cecum lumen and feces in pigs. Front. Microbiol. 9, 2626 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Doms, S. et al. Key features of the genetic architecture and evolution of host–microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice. eLife 11, e75419 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McKnite, A. M. et al. Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PLoS One 7, e39191 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leamy, L. J. et al. Host genetics and diet, but not immunoglobulin A expression, converge to shape compositional features of the gut microbiome in an advanced intercross population of mice. Genome Biol. 15, 552 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Bonder, M. J. et al. The effect of host genetics on the gut microbiome. Nat. Genet. 48, 1407–1412 (2016). This paper describes an early study on the effects of host genetics on the gut microbiome.

    Article 
    PubMed 

    Google Scholar
     

  • Wang, J. et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat. Genet. 48, 1396–1406 (2016). This early microbiome GWAS finds associations with the gene encoding for the vitamin D receptor.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ishida, S. et al. Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota. Commun. Biol. 3, 686 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rühlemann, M. C. et al. Genome-wide association study in 8956 German individuals identifies influence of ABO histo-blood groups on gut microbiome. Nat. Genet. 53, 147–155 (2021). This large GWAS identifies effects of the ABO blood group on the human gut microbiome.

    Article 
    PubMed 

    Google Scholar
     

  • Liu, X. et al. A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases. Cell Discov. 7, 9 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, X. et al. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome. Nat. Genet. 54, 52–61 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7738 participants of the Dutch Microbiome Project. Nat. Genet. 54, 143–151 (2022). This large GWAS of the human gut microbiome validates the association of variants at the LCT locus and finds that the association is modulated by lactose intake.

    Article 
    PubMed 

    Google Scholar
     

  • Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. 54, 134–142 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kolde, R. et al. Host genetic variation and its microbiome interactions within the human microbiome project. Genome Med. 10, 6 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scepanovic, P. et al. A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals. Microbiome 7, 130 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tomofuji, Y. et al. Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome–host interactions in the Japanese population. Cell Rep. 42, 113324 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Moitinho-Silva, L. et al. Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota. Nat. Commun. 13, 6204 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, X. et al. A genome-wide association study reveals the relationship between human genetic variation and the nasal microbiome. Commun. Biol. 7, 139 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fang, Z. Y. et al. Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization. Cell Host Microbe 32, 1838–1852.e5 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Enattah, N. S. et al. Identification of a variant associated with adult-type hypolactasia. Nat. Genet. 30, 233–237 (2002).

    Article 
    PubMed 

    Google Scholar
     

  • Rasinperä, H. et al. Transcriptional downregulation of the lactase (LCT) gene during childhood. Gut 54, 1660–1661 (2005).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garrido, D., Barile, D. & Mills, D. A. A molecular basis for bifidobacterial enrichment in the infant gastrointestinal tract. Adv. Nutr. 3, 415S–421S (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Itan, Y., Jones, B. L., Ingram, C. J. E., Swallow, D. M. & Thomas, M. G. A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol. Biol. 10, 36 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jajosky, R. P. et al. ABO blood group antigens and differential glycan expression: perspective on the evolution of common human enzyme deficiencies. iScience 26, 105798 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Mäkivuokko, H. et al. Association between the ABO blood group and the human intestinal microbiota composition. BMC Microbiol. 12, 94 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rausch, P. et al. Multigenerational influences of the Fut2 gene on the dynamics of the gut microbiota in mice. Front. Microbiol. 8, 991 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Folseraas, T. et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J. Hepatol. 57, 366–375 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rausch, P. et al. Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc. Natl Acad. Sci. USA 108, 19030–19035 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wacklin, P. et al. Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLoS One 6, e20113 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tong, M. et al. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J. 8, 2193–2206 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, H. et al. ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs. Nature 606, 358–367 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ségurel, L. et al. The ABO blood group is a trans-species polymorphism in primates. Proc. Natl Acad. Sci. USA 109, 18493–18498 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Burgess, S. et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open. Res. 4, 186 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Davey Smith, G. & Ebrahim, S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32, 1–22 (2003).

    Article 

    Google Scholar
     

  • Sanderson, E. et al. Mendelian randomization. Nat. Rev. Methods Prim. 2, 6 (2022).

    Article 

    Google Scholar
     

  • Sanna, S. et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat. Genet. 51, 600–605 (2019). Together with Liu et al. (2022), this work exemplifies the use of Mendelian randomization to identify potential causal effects of the microbiome on human health.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arora, T. & Tremaroli, V. Therapeutic potential of butyrate for treatment of type 2 diabetes. Front. Endocrinol. 12, 761834 (2021).

    Article 

    Google Scholar
     

  • Stender, S., Gellert-Kristensen, H. & Smith, G. D. Reclaiming Mendelian randomization from the deluge of papers and misleading findings. Lipids Health Dis. 23, 286 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wade, K. H. & Hall, L. J. Improving causality in microbiome research: can human genetic epidemiology help? Wellcome Open. Res. 4, 199 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Morgan, X. C. et al. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol. 16, 67 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Häsler, R. et al. Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease. Gut 66, 2087–2097 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Omar Al-Hassi, H., Ng, O. & Brookes, M. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 67, 395 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Bennet, S. M. P. et al. Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation: XXXX. Neurogastroenterol. Motil. 30, e13468 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019). Together with Morgan et al. (2015), this key paper describes associations between the gut microbiome and host gene regulation in IBD.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dayama, G., Priya, S., Niccum, D. E., Khoruts, A. & Blekhman, R. Interactions between the gut microbiome and host gene regulation in cystic fibrosis. Genome Med. 12, 12 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mars, R. A. T. et al. Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell 182, 1460–1473.e17 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chang, H. et al. Unveiling the links between microbial alteration and host gene disarray in Crohn’s disease via TAHMC. Adv. Biol. 8, e2400064 (2024).

    Article 

    Google Scholar
     

  • Mirsepasi-Lauridsen, H. C., Vallance, B. A., Krogfelt, K. A. & Petersen, A. M. Escherichia coli pathobionts associated with inflammatory bowel disease. Clin. Microbiol. Rev. 32, e00060-18 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, S. et al. Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn’s disease: a multi-omics Mendelian randomization study. BMC Med. 21, 179 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Priya, S. et al. Identification of shared and disease-specific host gene–microbiome associations across human diseases using multi-omic integration. Nat. Microbiol. 7, 780–795 (2022). This important study elucidates patterns of host gene–microbiome interactions across diseases.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fyhrquist, N. et al. Microbe–host interplay in atopic dermatitis and psoriasis. Nat. Commun. 10, 4703 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Edfeldt, G. et al. Distinct cervical tissue-adherent and luminal microbiome communities correlate with mucosal host gene expression and protein levels in Kenyan sex workers. Microbiome 11, 67 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, Z. et al. Airway host–microbiome interactions in chronic obstructive pulmonary disease. Respir. Res. 20, 113 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yan, Z. et al. Multi-omics analyses of airway host–microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions. Nat. Microbiol. 7, 1361–1375 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Johnson, K. E. et al. Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome. Cell Genom. 4, 100638 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Y. et al. Exploratory multi-omics analysis reveals host–microbe interactions associated with disease severity in psoriatic skin. EBioMedicine 105, 105222 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, B. et al. Characteristics of vaginal microbes and classification of the vaginal microbiome. Preprint at bioRxiv https://doi.org/10.1101/2023.08.16.553525 (2023).

  • Galeano Niño, J. L. et al. Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer. Nature 611, 810–817 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cai, L. et al. Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma. NPJ Biofilms Microbiomes 10, 39 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Camp, J. G. et al. Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res. 24, 1504–1516 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sommer, F., Nookaew, I., Sommer, N., Fogelstrand, P. & Bäckhed, F. Site-specific programming of the host epithelial transcriptome by the gut microbiota. Genome Biol. 16, 62 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pan, W.-H. et al. Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development. Genome Med. 10, 27 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davison, J. M. et al. Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor hepatocyte nuclear factor 4ɑ. Genome Res. 27, 1195–1206 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Richards, A. L. et al. Gut microbiota has a widespread and modifiable effect on host gene regulation. mSystems 4, e00323–18 (2019). Together with Davison et al. (2017), this key paper investigates the mechanisms of host gene–microbiome cross-talk.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Semenkovich, N. P. et al. Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes. Proc. Natl Acad. Sci. USA 113, 14805–14810 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dirksen, P. et al. CeMbio—the Caenorhabditis elegans microbiome resource. G3 10, 3025–3039 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, W. et al. The inducible response of the nematode Caenorhabditis elegans to members of its natural microbiota across development and adult life. Front. Microbiol. 10, 1793 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loomis, K. H. et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome 9, 22 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brusilovsky, M. et al. Host–microbiota interactions in the esophagus during homeostasis and allergic inflammation. Gastroenterology 162, 521–534.e8 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Meisel, J. S. et al. Commensal microbiota modulate gene expression in the skin. Microbiome 6, 20 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ansari, I. et al. The microbiota programs DNA methylation to control intestinal homeostasis and inflammation. Nat. Microbiol. 5, 610–619 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Krautkramer, K. A. et al. Diet–microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol. Cell 64, 982–992 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuang, Z. et al. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science 365, 1428–1434 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ryan, F. J. et al. Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease. Nat. Commun. 11, 1512 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nshanian, M. et al. Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression. Nat. Metab. 7, 196–211 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muehlbauer, A. L. et al. Interspecies variation in hominid gut microbiota controls host gene regulation. Cell Rep. 37, 110057 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qin, Y. et al. An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Genome Biol. 19, 7 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Drayman, N., Patel, P., Vistain, L. & Tay, S. HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations. eLife 8, e46339 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lötstedt, B., Stražar, M., Xavier, R., Regev, A. & Vickovic, S. Spatial host–microbiome sequencing reveals niches in the mouse gut. Nat. Biotechnol. 42, 1394–1403 (2024). Together with Galeano Niño et al. (2022), this notable paper describes spatial profiling of host–microbiome interactions.

    Article 
    PubMed 

    Google Scholar
     

  • Massaquoi, M. S. et al. Cell-type-specific responses to the microbiota across all tissues of the larval zebrafish. Cell Rep. 42, 112095 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Willms, R. J., Jones, L. O., Hocking, J. C. & Foley, E. A cell atlas of microbe-responsive processes in the zebrafish intestine. Cell Rep. 38, 110311 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Puschhof, J. et al. Intestinal organoid cocultures with microbes. Nat. Protoc. 16, 4633–4649 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Williamson, I. A. et al. A high-throughput organoid microinjection platform to study gastrointestinal microbiota and luminal physiology. Cell. Mol. Gastroenterol. Hepatol. 6, 301–319 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sanna, S., Kurilshikov, A., van der Graaf, A., Fu, J. & Zhernakova, A. Challenges and future directions for studying effects of host genetics on the gut microbiome. Nat. Genet. 54, 100–106 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Xu, L., Paterson, A. D., Turpin, W. & Xu, W. Assessment and selection of competing models for zero-inflated microbiome data. PLoS One 10, e0129606 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fisher, C. K. & Mehta, P. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression. PLoS One 9, e102451 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weissbrod, O., Rothschild, D., Barkan, E. & Segal, E. Host genetics and microbiome associations through the lens of genome wide association studies. Curr. Opin. Microbiol. 44, 9–19 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Sham, P. C. & Purcell, S. M. Statistical power and significance testing in large-scale genetic studies. Nat. Rev. Genet. 15, 335–346 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Chetty, A. & Blekhman, R. Multi-omic approaches for host–microbiome data integration. Gut Microbes 16, 2297860 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lynch, J. et al. HOMINID: a framework for identifying associations between host genetic variation and microbiome composition. Gigascience 6, 1–7 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mills, R. H. et al. Multi-omics analyses of the ulcerative colitis gut microbiome link Bacteroides vulgatus proteases with disease severity. Nat. Microbiol. 7, 262–276 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Poretsky, R., Rodriguez-R, L. M., Luo, C., Tsementzi, D. & Konstantinidis, K. T. Strengths and limitations of 16S rRNA gene amplicon sequencing in revealing temporal microbial community dynamics. PLoS One 9, e93827 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Durazzi, F. et al. Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota. Sci. Rep. 11, 3030 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sharafutdinov, I. et al. A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development. Cell Host Microbe 31, 1345–1358.e6 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Berthenet, E. et al. A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk. BMC Biol. 16, 84 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sczyrba, A. et al. Critical assessment of metagenome interpretation—a benchmark of metagenomics software. Nat. Methods 14, 1063–1071 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meisel, J. S. et al. Skin microbiome surveys are strongly influenced by experimental design. J. Invest. Dermatol. 136, 947–956 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Deissová, T. et al. 16S rRNA gene primer choice impacts off-target amplification in human gastrointestinal tract biopsies and microbiome profiling. Sci. Rep. 13, 12577 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elie, C. et al. Comparison of DNA extraction methods for 16S rRNA gene sequencing in the analysis of the human gut microbiome. Sci. Rep. 13, 10279 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Allaband, C. et al. Time of sample collection is critical for the replicability of microbiome analyses. Nat. Metab. 6, 1282–1293 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nishijima, S. et al. Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations. Cell 188, 222–236.e15 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Pallister, T. et al. Food preference patterns in a UK twin cohort. Twin Res. Hum. Genet. 18, 793–805 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Fildes, A. et al. Nature and nurture in children’s food preferences. Am. J. Clin. Nutr. 99, 911–917 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Goodrich, J. K., Davenport, E. R., Waters, J. L., Clark, A. G. & Ley, R. E. Cross-species comparisons of host genetic associations with the microbiome. Science 352, 532–535 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Corrêa, R. O. et al. Inulin diet uncovers complex diet–microbiota–immune cell interactions remodeling the gut epithelium. Microbiome 11, 90 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shinn, L. M. et al. Fecal metagenomics to identify biomarkers of food intake in healthy adults: findings from randomized, controlled, nutrition trials. J. Nutr. 154, 271–283 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Diener, C. et al. Metagenomic estimation of dietary intake from human stool. Nat. Metab. 7, 617–630 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Zuppinger, C. et al. Performance of the digital dietary assessment tool MyFoodRepo. Nutrients 14, 635 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abdill, R. J., Adamowicz, E. M. & Blekhman, R. Public human microbiome data are dominated by highly developed countries. PLoS Biol. 20, e3001536 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sirugo, G., Williams, S. M. & Tishkoff, S. A. The missing diversity in human genetic studies. Cell 177, 1080 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • McCarthy, M. I. et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 9, 356–369 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    Article 
    PubMed 

    Google Scholar
     

  • Yang, J. et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat. Genet. 43, 519–525 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boyle, E. A., Li, Y. I. & Pritchard, J. K. An expanded view of complex traits: from polygenic to omnigenic. Cell 169, 1177–1186 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, F. et al. The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases. Microbiome 8, 145 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lloyd-Price, J. et al. Strains, functions and dynamics in the expanded human microbiome project. Nature 550, 61–66 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weiss, S. et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5, 27 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luca, F., Kupfer, S. S., Knights, D., Khoruts, A. & Blekhman, R. Functional genomics of host–microbiome interactions in humans. Trends Genet. 34, 30–40 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gloor, G. B., Macklaim, J. M., Pawlowsky-Glahn, V. & Egozcue, J. J. Microbiome datasets are compositional: and this is not optional. Front. Microbiol. 8, 2224 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Franzosa, E. A. et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nat. Methods 15, 962–968 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar