Genetics and the Microbiome
The role of the gut microbiome on gene expression (epigenetics), and the influence of genetics on shaping our microbiomes
General:
It’s time to admit that genes are not the blueprint for life (Feb 2024) https://www.nature.com/articles/d41586-024-00327-x
Eye diseases long thought to be purely genetic might be caused in part by bacteria that escape the gut and travel to the retina (Feb 2024, mice) https://www.nature.com/articles/d41586-024-00562-2 CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.
It is known that certain genes, which are shared by both Crohn’s disease (CD) and ulcerative colitis (UC) patients, may show a predisposition to the development of IBD. A new study reveals that the IBD disease risk previously related to genetics is partly mediated by the gut microbiome. (Mar 2019) https://www.gutmicrobiotaforhealth.com/en/new-research-sheds-light-on-the-effects-of-inflammatory-bowel-disease-risk-alleles-on-gut-bacterial-taxa/
Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice (2021) https://www.nature.com/articles/s41598-020-79538-x
Dissecting the contribution of host genetics and the microbiome in complex behaviors (2021, mice) https://medicalxpress.com/news/2021-03-microbes-key-neurological-disorders.html
HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome (April 2019) https://www.rheumatologyadvisor.com/home/topics/ankylosing-spondylitis/hla-alleles-with-risk-for-ankylosing-spondylitis-rheumatoid-arthritis-affect-gut-microbiome/ "The results support the hypothesis that HLA alleles may cause or increase the risk for AS or RA by interaction with the intestinal microbiome"
Impact of genetics on the microbiome:
For:
Gut microbiota composition in colorectal cancer patients is genetically regulated (Jul 2022, n=93) https://www.nature.com/articles/s41598-022-15230-6
Gut microbiome influenced by host's genetics. Gut bacteria in mice co-evolve with their hosts. https://www.sciencedaily.com/releases/2022/08/220824103045.htm 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 (Jul 2022)
Genetically determined hypertensive phenotype affects gut microbiota composition, but not vice versa (Mar 2021, rats) https://journals.lww.com/jhypertension/Abstract/2021/09000/Genetically_determined_hypertensive_phenotype.7.aspx
Gut microbiome heritability is nearly universal but environmentally contingent (Jul 2021, wild baboons) https://science.sciencemag.org/content/373/6551/181 "Controlling for diet, age, and socioecological variation, 97% of microbiome phenotypes were significantly heritable. Heritability was typically low (mean = 0.068)". Commentary: https://science.sciencemag.org/content/373/6551/159
Associations of Genetic Variants Contributing to Gut Microbiota Composition in Immunoglobin A Nephropathy (Jan 2021) https://msystems.asm.org/content/6/1/e00819-20
International study finds specific changes in DNA affected both the existence and amount of particular bacteria in the gut (Jun 2020, n=3890) Genome-wide associations of human gut microbiome variation and implications for causal inference analyses https://www.eurekalert.org/pub_releases/2020-06/uob-prr062220.php
Genetic differences in the immune system shape the microbiome. Polymorphic immune mechanisms regulate commensal repertoire (Oct 2019, mice) https://medicalxpress.com/news/2019-10-genetic-differences-immune-microbiome.html
Patient genetics is linked to chronic wound microbiome composition and healing (Jun 2020, n=190) https://www.the-scientist.com/the-literature/long-lasting-wound-infections-linked-to-microbes-and-genetics-67872
Murine Genetic Background has a Stronger Impact on the Composition of the Gut Microbiota than Maternal Inoculation or Exposure to Unlike Exogenous Microbiota (July 2019) https://www.asm.org/Press-Releases/2019/July/Mouse-Genetics,-More-than-Environment,-Influences
Human Salivary Amylase Gene Copy Number Impacts Oral and Gut Microbiomes (Apr 2019) https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(19)30113-1 "This study establishes AMY1-CN as a genetic factor associated with microbiome composition and function"
Species identity dominates over environment in shaping the microbiota of small mammals (Mar 2019): https://onlinelibrary.wiley.com/doi/pdf/10.1111/ele.13240
Diet matters less than evolutionary relationships in shaping gut microbiome. Study is the largest published comparative dataset of non-human primate gut microbiomes to date. Evolutionary trends in host physiology outweigh dietary niche in structuring primate gut microbiomes (2018): https://www.nature.com/articles/s41396-018-0175-0 - https://www.eurekalert.org/pub_releases/2018-07/nu-dml073018.php
Fecal metabolome was found to be only modestly influenced by host genetics (heritability (H2)= 17.9%) (2018): https://www.nature.com/articles/s41588-018-0135-7
Host genetics strongly influences the composition of vaginal microbiota. Host obesity significantly increased the diversity of the vaginal microbiota in association with Prevotella. (2017): https://www.sciencedirect.com/science/article/pii/S1931312816304887
Association between Human Genetic Variants and the Vaginal Bacteriome of Pregnant Women (Jul 2021, n= 359) https://journals.asm.org/doi/10.1128/mSystems.00158-21
The effect of host genetics on the gut microbiome (2016): https://www.nature.com/articles/ng.3663
Genetic Association with Subgingival Bacterial Colonization in Chronic Periodontitis (2018): http://www.mdpi.com/2073-4425/9/6/271/htm "strong evidence supporting a direct connection between the host’s genetic profile and the occurrence of chronic periodontitis-associated bacteria"
Sea lion and dolphin bacterial communities were very different, despite originating from animals living in the same water and eating the same diet. Dolphin bacterial suites were a closer match to one another, regardless of location, than to those of sea lions. (2017): https://blogs.scientificamerican.com/guest-blog/the-secret-lives-of-marine-mammal-microbes/
Host species determined gut microbial assemblies, even if fed with the same food (fish vs mice, 2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0471-y "The extensive divergences in gut microbiota between mice and fish strongly indicate that host species determines an essential role in microbial assemblages [6], consistent with observations from previous studies of different mammals [21] and other wild and domesticated animals [22, 23]."
Review, 2017: Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481955/ - "Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity"
By distilling associations between ethnicity and gut microbiota variation in two American datasets including 1,673 individuals, we report 12 microbial genera and families that reproducibly vary by ethnicity. These results demonstrate recurrent associations between specific taxa in the gut microbiota and ethnicity, providing hypotheses for examining specific members of the gut microbiota as mediators of health disparities (2018): https://www.biorxiv.org/content/early/2018/06/08/342915
Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs (2017): http://www.genetics.org/content/206/3/1637.long
The effect of heritability and host genetics on the gut microbiota and metabolic syndrome (2016): http://gut.bmj.com/content/66/6/1031.long
The presence of genetic risk variants within PTPN2 and PTPN22 is associated with intestinal microbiota alterations in Swiss IBD cohort patients (2018): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199664
Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition (2018): https://www.nature.com/articles/s41586-018-0395-5 | News article on this study: https://www.nature.com/articles/d41586-018-05861-z
Human genetics shape the gut microbiome (2014): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255478/
Association between the ABO blood group and the human intestinal microbiota composition (2016): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485159/ "ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota"
Host mitochondria influence gut microbiome diversity: A role for ROS (July 2019) https://stke.sciencemag.org/content/12/588/eaaw3159 "These data suggest that microbiome diversity is genetically encoded. That the mitochondrial genotype modulates both ROS production and the species diversity of the gut microbiome"
Diet during Pregnancy and Infancy and the Infant Intestinal Microbiome (2018): https://doi.org/10.1016/j.jpeds.2018.07.066 "The relationship between breastfeeding status and intestinal microbiome composition varies by child race/ethnicity. Although our findings suggest that race/ethnicity modifies the relationship between diet and the microbiome, this observation needs to be replicated. If confirmed, this relationship may suggest early genetic influences or other unmeasured factors in the response of the microbiome to the diet in different ethnic groups."
Early‐life exposure to gut microbiota from disease protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice (2018): https://doi.org/10.1111/imcb.12201
Deletion of poly(ADP‑ribose) polymerase-1 changes the composition of the microbiome in the gut (2018): http://dx.doi.org/10.3892/mmr.2018.9474
The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis (2018): https://doi.org/10.1016/j.chom.2018.08.009
IL23R-protective coding variant promotes beneficial bacteria and diversity in the ileal microbiome in healthy individuals without inflammatory bowel disease (2018): https://doi.org/10.1093/ecco-jcc/jjy188 "The observation of low diversity and low abundance of beneficial bacteria in healthy control subjects carrying the IL23R (rs11209026) wild-type GG genotype indicates that the gut microbiome is influenced by host genetics and is altered prior to disease diagnosis"
Against:
The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596345/ - https://www.sciencedaily.com/releases/2017/09/170912102810.htm
Weizmann researchers were surprised to discover that the host’s genetics play a very minor role in determining microbiome composition – only accounting for about 2% of the variation between populations (2018): https://www.technologynetworks.com/tn/news/study-casts-doubt-on-gut-microbiotas-genetic-influence-298078 - https://www.nature.com/articles/nature25973 - weak study too high up on the taxonomy.
Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction (2018): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790872/
Structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. (2017): https://link.springer.com/article/10.1007%2Fs00284-016-1176-8
Social relationships, social isolation, and the human gut microbiota (2018): https://doi.org/10.1101/428938 "spouses have more similar microbiota and more bacterial taxa in common than siblings, with no observed differences between sibling and unrelated pairs. The differences between unrelated individuals and married couples was driven entirely by couples who reported close relationships"
A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals (Sept 2019) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0747-x "The lack of any significant results in the genome-wide association analyses, on the other hand, indicates that common human genetic variants of large effects do not play a major role in shaping the gut microbiome diversity observed in healthy populations"
Other:
Existing studies are underpowered to identify microbiome-associated genetic variants (2018): https://www.sciencedirect.com/science/article/pii/S1369527418300079
Oral microbiota of twins could be distinguished from each other despite the similarities in genetic make-up, living environment, and lifestyle (2018): https://www.nature.com/articles/s41598-018-25636-w
Gut and skin phage-bacteria network structures were person-specific and not conserved among cohabitating family members (2018): http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006099
Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography [Aug 2018] https://www.nature.com/articles/s41591-018-0160-1 Ethnicity contributed to explain the interindividual dissimilarities in gut microbiota composition.
Gut microbiome regulates epigenetics:
Review, 2013: Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis: https://onlinelibrary.wiley.com/doi/full/10.1111/gbb.12109 "To date, there is rapidly increasing evidence for host-microbe interaction on virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behavior and cognition has significantly contributed to establish the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept"
Review, 2017: Host–microbiota interactions: epigenomic regulation https://www.sciencedirect.com/science/article/pii/S0952791516301558
Review, 2018: Early Disruption of the Microbiome Leading to Decreased Antioxidant Capacity and Epigenetic Changes: Implications for the Rise in Autism https://doi.org/10.3389/fncel.2018.00256
Perspective, 2019: Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism https://www.frontiersin.org/articles/10.3389/fgene.2019.00638/full
Microbes Help Orchestrate How the Gut Uses its Genes. Mice without microbes rely on an entirely different set of genes to digest fat. (May 2022) Transcriptional integration of distinct microbial and nutritional signals by the small intestinal epithelium https://today.duke.edu/2022/05/microbes-help-orchestrate-how-gut-uses-its-genes
The Gut Microbiota Modulates Gene Expression in the Kidney (May 2022, mice) https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.R2348
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues (2016) https://www.sciencedaily.com/releases/2016/11/161123124256.htm
Gut microbiota has a widespread and modifiable effect on host gene regulation (2019) https://msystems.asm.org/content/4/5/e00323-18