The human gut contains trillions of microorganisms–collectively known as the Gut microbiome. Having the primary function in the digestive system, we now know a lot more about these immigrants.
These microorganisms can be of thousands of different species and their collective genome contains > 150 times more genes than the human or mouse genome. Their gene content is often called our second genome. Like the host genome, the gut microbiome composition and diversity in each individual are unique.
It also has an important function in boosting immunity, preventing disease, fighting against infection and improving mental health. But, people often know less about the association between our gut microbiome and genetics!
Your guess… is correct! There is a strong association between our DNA and microbiome.
Doubt! Let’s decode several studies that explain the host genetics and microbiome relationship.
Related article: Antibiotics Could Be Weakening Cancer Treatment — Here’s Why
Key Topics:
How our gut microbiome and genetics are linked:
It’s a two-way relationship.
Certain genetic or gene variants directly affect the microbiome composition or a specific microbe within! Similarly, a change in microbiome composition results in either genetic or epigenetic alterations.
A study published by the American Society for Microbiology (ASM) showed that the gut microbiome can actively control host gene expression.
After exposing healthy people’s colonic epithelial cells to live gut microbes, researchers noticed notable alterations in the expression of more than 5,000 host genes. Of these, characteristics of biological complexity were associated with 588 gene-microbe associations.
This study further revealed that one bacterium, Collinsella, when administered in titrated doses, alters transcriptional factor binding and chromatin accessibility and thereby changes the expression profile of genes.
Meaning, the gut microbiome causes gene expression changes and leads to epigenetic alterations. Another study published in the journal Poultry Science by Xu et al. (2025) microbiome imbalance leads to differential expression of 298 genes in chicken muscle tissue.
Certain microbes produce toxins. Those toxins activate DNase abnormally or exhibit DNase activity on their own, leading to double-stranded DNA Breaks. For instance, Colibactin, released by E. coli.
These mutations can cause various types of cancer, explains the study published in The ISME Journal.
Cellular oxidative stress leads to DNA damage. That’s known to us. But a study published in Frontiers gives a broad idea of the relationship between gut microbiome and oxidative stress.
The gut microbiota has an impact on oxidative stress by means of metabolite synthesis, regulation of antioxidant enzymes, and maintenance of gut homeostasis. In contrast, oxidative stress has the potential to influence the gut microbiome by promoting dysbiosis.
This review outlines how gut microorganisms ferment dietary fibres and produce short-chain fatty acids(SCFAs) such as acetate, propionate, and butyrate. This causes oxidative stress in the gut.
It also explains how certain bacteria in our gut, like bifidobacterium longum, lactobacillus plantarum and L. rhamnosus play a role in enhancing the antioxidant defenses by the production of key enzymes that regulate redox balance and protect host cells from reactive oxygen species (ROS).
Disruption in this entire system weakens our immune system, leads to chronic inflammation, disease and DNA damage.
Now, let’s see the other side of the story. How do gene or DNA variants affect the microbiome?
A review published by Hall et al. (2017) in Nature Reviews Genetics reviewed studies that showed the likely link between gene variants and gut microbiome composition.
They concluded that many human gene variants have been linked with the microbiome composition in our gut. For example, the variants of LCT, NOD2 and FUT2 substantially impact the gut microbe composition.
Key takeaways:
All these studies that we discussed in this article give us insights into the complex relationship between our gut microbes and genetics. Let’s summarize them.
- As stated, the relationship is two-way; genetic changes alter microbiota and vice versa.
- Certain gene variants alter the microbiome composition.
- Epigenetic changes also alter the pathways that lead to changes in microbiome composition.
- Gut microbiota causes DNA damage or alters the epigenetic profile of genes.
- It can even produce double-stranded DNA damage and lead to conditions like cancer.
Let me just quote one last study related to the complex interplay between the microbiome, genetics and aging. A review article by Chakrabarti et al. (2025) explained this complex interplay.
Age substantially reduces cellular and physical capabilities, which heightens the risk of diseases and diminishes the body’s resilience to stress. A significant contributor to this decline is the change in the gut microbiome.
As we age, there is a reduction in the beneficial bacterial population. This reduces immune capabilities, triggers chronic inflammation, and worsens DNA damage. Furthermore, this escalates genomic instability by promoting oxidative stress and boosting DNA damage.
Results! age-associated disease progression.
Related article: New Discovery: How a Novel Epigenetic Regulator Impacts Gene Expression
Wrapping up:
What’s the point here? We should have considered our gut microbiota as an important part of ourselves. It’s our ‘second brain’ that is highly sensitive to food, environment and even our thoughts.
This article reveals that genetics (our DNA) is also an important contributor to our unicellular universe’s well-being. More understanding of this relationship will help us to strengthen our tiny universe and our DNA.
Scientifically, such information helps tailor interventions for diseases such as obesity, inflammatory bowel diseases, cardiovascular conditions, colorectal cancer, and more.
Long story short!
Consume fibers, probiotics and healthy food, and make your gut happy. If they are happy, you are happy!
Sources:
- Hall, A., Tolonen, A. & Xavier, R. Human genetic variation and the gut microbiome in disease. Nat Rev Genet 18, 690–699 (2017). https://doi.org/10.1038/nrg.2017.63.
- Xu, Y., Huang, Y., Wei, S., Tian, J., Huang, Y., Nie, Q., & Zhang, D. (2025). Changes in gut microbiota affect DNA methylation levels and development of chicken muscle tissue. Poultry Science, 104(3), 104869. https://doi.org/10.1016/j.psj.2025.104869.
- Sun J, Chen F, Wu G. Potential effects of gut microbiota on host cancers: focus on immunity, DNA damage, cellular pathways, and anticancer therapy. ISME J. 2023 Oct;17(10):1535-1551. doi: 10.1038/s41396-023-01483-0. Epub 2023 Aug 8. PMID: 37553473; PMCID: PMC10504269.
- Chakrabarti SK, Chattopadhyay D. Aging and DNA Damage: Investigating the Microbiome’s Stealthy Impact – A Perspective. Explor Res Hypothesis Med. 2025;10(2):106-121. doi: 10.14218/ERHM.2024.00046. https://doi.org/10.1038/nrg.2017.131.
- Sun Y, Wang X, Li L, Zhong C, Zhang Y, Yang X, Li M and Yang C (2024) The role of gut microbiota in intestinal disease: from an oxidative stress perspective. Front. Microbiol. 15:1328324.
- Richards, Allison L., Amanda L. Muehlbauer, Adnan Alazizi, Michael B. Burns, Anthony Findley, Francesco Messina, Trevor J. Gould, et al. 2019. “Gut Microbiota Has a Widespread and Modifiable Effect on Host Gene Regulation.” Edited by Elizabeth A. Grice. MSystems 4 (5). https://doi.org/10.1128/msystems.00323-18.
- Waters JL, Ley RE. The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biol. 2019 Oct 28;17(1):83. doi: 10.1186/s12915-019-0699-4.
