Fish oil may be important to altering the microbiome, reducing anxiety

Last week we published a blog on the gut-brain axis, and the various associations between brain health and the gut microbiome.  One of the ailments we discussed was depression, which is often studied in mice by inducing early life stress on the mice.  One way to do this is by separating mice from their mothers for hours at a time at a young age.  The Maternal Separation model, as it is known, causes stress and anxiety in these mice, but more importantly, research has shown that it creates a dysbiosis of their gut microbiomes as well.  Many scientists believe the dysbiosis may be implicated in causing some of the stress phenotypes, and so reversing this dysbiosis could have therapeutic value.  Researchers from the University College Cork, in Cork Ireland, experimented with N-3 polyunsaturated fatty acids (PUFAs), like those found in fish oil, in these maternally separated mice, and found they may be important to preventing the dysbiosis.  They published their findings in the journal PLoS ONE.

In the study, the researchers separated mice into two groups, one underwent maternal separation, and the other had a normal upbringing.  Within each group the mice were separated into two more groups, one that received fish oil supplements and the other that didn’t.  Over the course of 17 weeks each groups’ feces were sampled for their microbiomes.  The Maternal separation tended to decrease the bacteroidetes to firmicutes ratio of the mice’s microbiome, which has previously been linked to depression in humans.  Interestingly, supplementation with the fish oil increased this ratio in those maternally separated mice.  In addition, the fish oil also increased the concentration of bacteria that were higher in non-separated mice, such as populations of Rikenella.  Finally, the fish oil increased the amount of butyrate producing bacteria, and as we have seen many times before, butyrate and other short chained fatty acids (SCFAs) are often associated with health.

Overall this study showed that fish oil shifted stressed mice’s microbiome to a more natural state, presumably helping them in the process.  While the scientists did not directly measure stress levels in these mice to support the microbiome connection, hopefully that will be part of a follow up study.  The scientists noted that fish oil is clinically shown to reduce inflammation, and made it a point to connect the stress in the mice to systemic inflammation.  Systemic inflammation is also mediated by the microbiome.  Indeed, people that have inflammation from IBD, for example, do tend to have more stress and anxiety.  In the end, fish oil could make for an interesting prebiotic to shift the microbiome, counteract inflammation, and improve mental health. 

Different types of dietary fat affect obesity through changes to the microbiome

A triglyceride molecule, the main constituent of lard.

Dietary fat comes in many in many different forms, such as saturated fats that come from foods like lard, and polyunsaturated fats that come from foods like fish oil.  It is generally believed that saturated fats lead to inflammation and obesity, but that polyunsaturated fats are healthier, and can counteract inflammation and promote healthy metabolism.  The role of the microbiome in mediating these effects is still unknown, but is beginning to be elucidated.  A team of researchers from Sweden, Belgium and Denmark showed that the lipids themselves alter the microbiome, which induces the characteristic inflammation associated with ingesting saturated fats.  Their results were published in the journal Cell Metabolism.

The scientists fed groups of mice identical diets that only differed in the type of fat that was consumed: lard composed of saturated fats, and fish oil composed of polyunsaturated fat.  As expected, the group that ate the saturated fat gained weight and had higher fasting glucose than those eating unsaturated fat.  When they measured the gut microbiomes of these mice, they discovered that the overall diversity of bacteria were much lower in the mice eating the saturated fat diet.  Next, the scientists measured the contents of the blood of the mice and discovered that there were higher levels of bacterial metabolites and bacterial components in the blood of mice eating the saturated fat diet.  Using complicated techniques that are beyond the scope of this blog, the researchers were able to trace the inflammation to an increase in specific receptors in the gut that are activated by bacteria from the saturated fat diet, including some specific toll like receptors (TLRs).  The scientists conducted a final experiment to show the importance of the microbiota, rather than the diet, in inducing these effects.  They transplanted the feces of both groups of mice into new, healthy mice.  The mice given the feces of the saturated fat group gained weight, whereas the ones given the microbiomes of the polyunsaturated fat group tended to lose weight.

The scientists believe that diets high in saturated fats upregulate specific immune system receptors that are activated by factors derived from the gut microbiome.  Moreover, these factors find their way into the blood much more easily after consuming saturated fat, as opposed to unsaturated fat, so they can easily activate these receptors.  After activation the factors lead to inflammation and obesity.  Overall, this research explains one of the reasons why polyunsaturated fats are healthier than saturated ones.  We know It’s not often anyone is faced with the choice between fish and lard, but after reading this study we recommend our readers go with the fish.