Gene Expression: Your gut microbiome has something to say

If you want to thrive on the outside, you need to thrive on the inside.

A vibrant and diverse microbiome is critical to optimal health and wellness.

Research continues to link an imbalance in gut microorganisms to type 2 diabetes, obesity, cancer, intestinal bowel diseases, autoimmune disease, and certain mental health conditions. How this happens on a cellular level is not completely understood.

But science is gaining ground and it may be all about epigenetics.

The connection between early childhood disease and the microbiome.

It’s long been suspected the global rise in allergic diseases is linked to industrial development and Westernization as it spreads throughout the world.  Whether this is due to changing diet and lifestyles, increased toxic exposure, or both, still seems to be open for debate.

What isn’t being debated is that these changes are affecting immune function and early childhood disease regardless of genetic backgrounds.

One possibility for this evolving disease pattern is an imbalance in the microbiome caused by the changing environment. The fact a healthy gut microbiota in early life impacts future health is providing clues as to why.

This was highlighted in a study that showed a significant relationship between the presence of the bacteria Clostridium difficile in the fecal samples of children who later developed food allergies.  The bacteria, known to cause colitis, is usually present after taking antibiotics and indicative of a gut imbalance.

Based on this premise, a laboratory model of the intestinal mucosal immune system was used to investigate the effects of two probiotics, Bifidobacterium breve and Lactobacillus rhamnosus. Study results showed that both can inhibit the translation of the interleukin genes IL-234 and IL-17, and CD40, all pro-inflammatory.

The increase in childhood asthma is now suspected to be the result of the hypermethylation of a gene crucial in lymphocyte regulation, Runx3, in utero.  The same process in genes associated with the immune system is also suspected of predisposing children to intestinal diseases such as colitis.  Some research has pointed to this being a result of a mother’s overexposure to folic acid, the synthetic form of folate, which can lead to hypermethylation.

In fact, new research has found a mothers gut microbiome, prior to or during pregnancy, may impact fetal development through her intestinal microbiota’s role in epigenetics.  

Butyrate, a small chain fatty acid (SCFA), produced by gut bacteria when fermenting dietary fibers, is known to be critical to gut health.  Its anti-inflammatory effect is in part a result of its ability to suppress the expression of NALP3, a gene known for triggering inflammation.

It was shown these SCFAs, produced by the gut and vaginal microbiota of pregnant women, can pass through the placenta and impact the development of the fetus.

Although more research is needed, initial findings point to the idea that a balanced and robust microbiome during pregnancy is as important to the health of a fetus as it is to the mother due to its ability to influence gene regulation.

How the microbiome influences gene expression.

One way in which the human microbiome impacts gene expression is through modifying DNA methylation and histone acetylation. 

An example of this is that short-chain fatty acids (SCFAs) have been shown to influence histone acetylation. Even a small change in diet can cause major shifts in SCFAs and other bacterial metabolites, which then could change gene expression for a variety of genes leading to more long-lasting effects.  

This view coincides with a new study published in Nature Microbiology where researchers integrated microbiome and host gene data to provide insights into their combined role in gastrointestinal diseases.

Using data from patients who suffered from colorectal cancer, inflammatory bowel disease, and irritable bowel syndrome, they were able to identify a common set of host genes and pathways that regulate gastrointestinal inflammation, gut barrier protection, and energy metabolism.

They found that gut microbes that have been implicated in all three diseases, such as Streptococcus, interact with different host pathways in each disease. It is shedding light on the idea that interplay between gut microbes and host gene regulation may be contributing to the root cause of gastrointestinal disorders.

Another study published in the American Society for Microbiology used intact fecal microbiota communities from five healthy individuals to look at whether it was possible to associate the gut microbiota with gene regulation in epithelial cells.

By measuring changes in transcription levels and chromatin accessibility in host cells, they identified over 5,000 genes that changed expression including 588 distinct associations between specific microbes and host genes.

They were also able to demonstrate predictable gene expression by manipulating the composition of the microbiome under natural and controlled conditions.

Some research has been able to connect microbes with specific gene expression.  Fusobacterium nucleatum, a bacteria that has been detected in higher abundance in colorectal cancer patients, has been shown to increase the proliferation of colon cancer cells in the lab by influencing the BRAF gene.

Other microbial species may trigger protective genes. Bifidobacterium adolescentis has been shown to inhibit the growth of colon cancer cells by upregulating tumor necrosis factors,(TNF).

Additional research findings.

Research is revealing additional ways the microbiome can influence gene expression:

• Transcription factors are host proteins that bind to DNA and regulate the transcription of genes. Elements of the microbiome bind directly to transcription factors, preventing gene expression.
• The microbiome influences the expression of genes which regulate detoxification pathways.
• In mice studies, modulation of the microbiome had dramatic effects on gene expression including Phase I enzymes, Phase II enzymes, transporters, and transcription factors. Additionally, expression of drug-metabolizing enzymes in the liver were significantly altered, demonstrating the causal role the microbiome may play in altering body-wide gene expression.
• In a mouse study, over half of the expressed genes in the GI tract were regulated by the microbiome.
• Studies conducted with zebrafish also demonstrated the impact of the microbiome on immunity, metabolism, and developmental gene regulation.
• Gut pathogens influence gene expression, either directly or indirectly, through immune stimulation by targeting specific RNAs for degradation or inhibiting their translation, dampening the immune response.
• The microbiome remodels the chromatin in intestinal epithelial cells, impacting gene expression.
• One important gene that is downregulated by the microbiome in obese mouse studies is Scd1, an important regulator of the amount of free-floating fatty acids and is responsible for combining them into triglyceride storage. Downregulation of Scd1 has been seen in patients with nonalcoholic fatty liver disease (NAFLD). It is possible that the microbiome, in an obese state, indirectly promotes the formation of NAFLD through gene modification.

Science is just beginning to understand the impact the microbiome has on genetic expression, but what has been discovered so far just serves to reinforce the fact the gut microbiome influences overall health throughout life in multiple ways, many of which have yet to be discovered.

It is known that gut balance is foundational to optimal health which is why understanding the microbiome and how it influences chronic conditions is such an important part of my Nutritional Endocrinology Practitioner Training (NEPT) program.

Connecting the clues left by chronic symptoms can be incredibly challenging, but with the education and support my students receive, they continue to help thousands of clients who were unable to find what they needed in the broken healthcare system.

My clients get the same support when they become members of my Empowered Self-Care Lab.

No one has to run this “health maze” alone. And if you stick with me, there will be a reward at the end of your journey – the kind of resources and support that empower you to bring the change so desperately needed to healthcare.

Yes, I may be able to do it without you, but I don’t want to.

Consider joining our community. 

Resources:

1. The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System – PMC

2. The relationship between the gut microbiome and host gene expression: a review – PMC

3. Gut Microbes can Impact Host Gene Expression | Genetics And Genomics

4. Gut Microbiota Has a Widespread and Modifiable Effect on Host Gene Regulation | mSystems

5. Early probiotics shape microbiota | Nature Microbiology

6. Impact of mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns | Environmental Epigenetics | Oxford Academic