Fish Oils: A powerful fuel for microbiome diversity and gastrointestinal health

The gut microbiome refers to the collection of trillions of microbes living within the gastrointestinal tract. Research shows that the microbiome has a profound impact on a variety of systems and plays crucial roles in digestive, immune and mental health. An imbalance in the intestinal microbiome may lead to a wide range of issues, ranging from occasional symptoms of digestive distress like gas and bloating, to broader systemic challenges such as obesity, diabetes, Alzheimer’s disease, inflammation, cancer, etc.

Positively influencing the microbiome is a major health goal for many consumers. Unfortunately, currently the focus has been on trying to influence the microbiome by “seeding” it with probiotics or through fecal transplants. This approach has limited benefits because it fails to address influencing the intestinal terrain and growth factors that nourish the microbiome towards health.

One of the key factors associated with a healthy intestinal microbiome is diversity. In this case diversity refers to a broad range of microbes both in terms of species and strains. While there are several key bacteria and yeast associated with a healthy microbiome, in general, the greater the diversity, the healthier the microbiome functions and the better health we enjoy.

Here is a little known fact: one of the greatest influencers of microbial diversity are the long-chain omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). But, it appears that fish oils providing higher levels of DHA to EPA exerts a more profound effect on the microbiome and greater anti-inflammatory effects, especially in the gut. The ideal ratio may be DHA 4: EPA 2: DPA 1. Interestingly, this ratio is very close to what is seen in wild salmon species.


Higher DHA levels to exert more profound effects on the microbiome

While many of the health benefits of omega-3 fatty acids are well known, the effects on the microbiome may be the most important to impacting human health. Here is what is currently known: DHA appears to be the key omega-3 for influencing the microbiome. DHA exerts this influence based upon circulating blood levels, DHA incorporated into cells that line the gastrointestinal tract, and by DHA acting as an intermediate to compounds known as D-series resolvins and protectins.

Resolvins are given that name because of their ability to resolve inflammation while protectins protect against inflammation from ever starting. These compounds help promote microbial diversity because higher gut microbiome diversity is linked to lower inflammation. The discovery of resolvins and protectins has helped understand why DHA supplementation reduces inflammatory conditions of the gastrointestinal tract and produces better effects than EPA in reducing gastrointestinal inflammation as well as improving the microbiome.

DHA is much more effective at dealing with the microbiome imbalance or “bacterial dysbiosis.” It also is more effective in reducing the inflammation in severe inflammatory bowel disorders, such as Crohn’s disease and ulcerative colitis. Not surprisingly, most of the bacteria associated with increased levels of serum DHA are also negatively correlated with Crohn’s disease severity and intestinal inflammation.

Some of the changes associated with higher DHA levels and greater microbial diversity are also thought to play a big role in fighting inflammation. There are other conditions as well including obesity. One of the classes of microbes associated with higher levels of circulating DHA are bacteria in the Lachnospiraceae family. These bacteria are quite important for gut health, as they are the main group bacteria in the human gut that transform dietary fiber into short-chain fatty acids (SCFAs).

These compounds, especially butyrate, have been shown to exert multiple beneficial effects and are the main energy source for the cells that line the colon. These bacteria are also critical in protecting against the overgrowth of unwanted bacteria such as Clostridium difficile infections. And, higher butyrate production is being also linked to benefiting weight loss, protecting against colon cancer, and improving conditions affecting the brain including autism.

Higher circulating DHA levels are also associated with higher levels of Lactobacillus and Bifidobacteria species. These bacteria are well known for the beneficial probiotic effects and are linked to helping offer protection against metabolic diseases, including obesity, diabetes, cardiovascular diseases, degenerative neurological diseases (Parkinson’s disease, Alzheimer’s disease and multiple sclerosis), as well as musculoskeletal conditions such as osteoporosis and gout.

Another superstar microbe boosted by DHA and EPA is Akkermansia muciniphila. This bacteria plays a critical role in the health of the mucin layer that protects the intestinal lining and maintains proper structure of the intestinal lining. Higher levels of Akkermansia muciniphila are associated with improved barrier function, reduced intestinal permeability (leaky gut), and improved insulin sensitivity. It is one of the most beneficial organisms in a healthy microbiome.

Higher DHA levels are also linked to higher concentrations in the fecal concentration of N-carbamylglutamate (NCG) that is manufactured by the microbiome. This compound produces some very interesting effects in promoting the health of intestinal cells. It reduces oxidative stress in the gut, preserves the integrity of the intestinal lining under stress, prevents intestinal permeability, and reduces intestinal inflammation—all extremely beneficial effects.


DHA produces favorable effects on butyrate production

One of the net results of the changes in the microbiome produced by DHA is increasing the level of butyrate-producing bacteria. Butyrate is the primary energy source of the cells that line the gastrointestinal tract. It is critical to gut health, as it not only is the fuel these cells need, but it also controls proper growth and replication. Butyrate helps maintain the function and integrity of the intestinal lining. It helps improve healthy gut barrier function and reduce the abnormal intestinal permeability often referred to as a leaky gut.

Butyrate is one of the key natural protectors against colon cancer. Not surprisingly, colon cancer risk is linked to lower numbers of bacteria that produce butyrate.

Butyrate protects against colon cancer not only through its effect on cellular energy and some antioxidant effects but also through effects on the immune system. For example, it positively influences the function of regulatory T-cells. These cells perform vital functions in helping the immune system recognize the difference between an infectious organism and our own body cells. Hence, it plays a key role in preventing autoimmunity.

Butyrate also demonstrates some anti-inflammatory effects especially in inflammatory bowel disease (e.g., Crohn’s disease and ulcerative colitis). Fish oil supplements have also been shown to be extremely beneficial in some studies in patients with IBD.

One of the key benefits of the ketogenic diet is that it increases the body’s production of butyrate. Many of the effects on appetite control and metabolism of a ketogenic diet are related to butyrate. Not surprisingly, increased microbiome production of butyrate is associated with prevention of obesity and type 2 diabetes. The changes in the microbiome produced by DHA are consistent with producing a microbiome profile supporting weight loss, improved metabolism and blood sugar control.


The ratio of EPA:DPA:DHA in systemic inflammation

In addition to a higher ratio of DHA to EPA exerting a greater influence on the microbiome, it is also showing greater anti-inflammatory effects. There have been a number of interesting studies comparing DHA to EPA or various ratios of each in inflammation. For example, the ComparED Study compared the effects on inflammation of EPA to DHA. Healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 2.7 g of the following supplements for periods of 10 weeks during the trial phases: EPA, DHA or corn oil. Supplementation with DHA compared with EPA showed a greater reduction in inflammatory markers such as C-reactive protein, interleukin-18, and tumor necrosis factor. The authors concluded, “DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids.”

In another study, subjects were given either 4 g of DHA or 4 g of EPA as part of a test meal to evaluate the effects of each on after-meal vascular function. What the results showed quite clearly was that DHA significantly reduced overall cardiovascular risk through the augmentation index while EPA had no effect. DHA produced a 13 percent decline, EPA 0 percent.

The beneficial effects are the result of DHA being metabolized into protective compounds known as oxylipins. While EPA can also be converted to its versions of these compounds, those derived from DHA are much more effective at reducing risk factors for heart disease. Another interesting finding is while higher blood ratios of either EPA or DHA to arachidonic acid (AA) are associated with a reduced risk of heart disease, in men only a high DHA to AA offers this protection.


Final comments

While the science of how to influence the microbiome is in its infancy, there is a pattern that is emerging and it focuses not on probiotics, but rather how to influence the terrain of the gastrointestinal tract. The growth of microorganisms in our intestinal tract is a lot like the planting of grass. If the lawn is overrun with weeds, competing grass types, and the soil is poor or arid, all the grass seed in the world is not going to produce a lush green lawn. The focus should be on improving the terrain first to see the desired change. It appears that the important factors to promote that proper intestinal terrain are the omega-3 fatty acids. In particular, DHA. VR



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