Considering that diet is—together with medication—one of the major influencing factors with regards to gut microbiota composition, research is now focusing on how dietary nutrients may affect gut microbial communities. Specifically, an association was previously found between essential omega-3 fatty acid DHA (docosahexaenoic acid) and gut microbiome diversity in healthy elderly people. However, evidence from randomized trials assessing the effect of omega-3 polyunsaturated fatty acids (PUFA) on human gut microbiota is scarce.

A new randomized clinical trial, led by Dr. Mark Hull from the Institute of Biomedical and Clinical Sciences at the University of Leeds (United Kingdom), has found that a daily intake of 4g of eicosapentaenoic and docosahexaenoic acids may lead to reversible changes in specific gut bacteria.

The researchers analyzed the effects of oral high-dose omega-3 PUFA on the fecal microbiota of 22 healthy middle-aged volunteers (median age 57 years; median body mass index 27 kg/m2). A combination of 2 g/day eicosapentaenoic acid (EPA) and 2 g/day DHA were administered in capsules or drinks over an 8-week period in a randomized cross-over design. After each intervention, there was a washout period of 12 weeks. Fecal samples for microbiome analysis were collected at five time-points and omega-3 fatty acid levels were measured in red blood cell (RBC) membranes.

By and large, the effect of interindividual variability overcame the effect of the short-term omega-3 PUFA intervention on the gut microbiome composition. This was reflected by the fact that omega-3 PUFA supplementation, in either capsule or drink form, did not drive any gut microbiota taxonomic shift or changes in a and b diversity at the end of the study compared with baseline.

However, omega-3 PUFA interventions led to specific changes at family and genus levels, which returned to baseline once the intervention was complete. At the family level, Clostridiaceae, Sutterellaceae and Akkermansiaceae increased at the end of both interventions. At the genus level, Bifidobacterium, Lactobacillus, Oscillospira and Lachnospira increased. In contrast, there was a drop in the abundance of Coprococcus and Faecalibacterium.

The functional consequences of the increase in short-chain fatty acid producers—Bifidobacterium, Lactobacillus, Lachnospira and Roseburia—after the 8 weeks of omega-3 PUFA supplementation deserves further research. Researchers hypothesize that these findings might explain the role of SCFA signaling in omega-3 PUFA chemopreventive activity, whereas mechanistic studies are needed to resolve the matter.

The type of omega-3 PUFA administration (capsules vs drinks) also had a different effect on the abundance of genera at the end of the study. For example, the increase in both Roseburia and Lachnospira was only observed during the drink intervention.

On the other hand, microbiome changes did not correlate with omega-3 PUFA exposure quantified with RBC omega-3 fatty acid incorporation or development of omega-3 PUFA-induced diarrhea.

Furthermore, incorporation of omega-3 PUFA within RBC did not vary depending on the type of formulation (capsules vs drinks). However, EPA and DHA administered in drinks led to a larger decrease in omega-6 PUFA arachidonic acid (AA) compared with capsules. This larger drop in AA content explained the increase in the omega-3:omega-6 ratio—a commonly used biomarker for assessing omega-3 PUFA bioactivity—after consumption of drinks compared with capsules.

As for adverse reactions from the intervention, some patients experienced minor and moderate dyspeptic symptoms and diarrhea.

In conclusion, these findings show that even short-term interventions driven by omega-3 PUFA may lead to reversible changes in the gut microbiota, which can only be appreciated at the family and genus level. On the other hand, the fact that the food matrix drives differential changes in the gut microbiota opens the avenue for taking them into account as a confounder in human nutrition microbiome studies.



Watson H, Mitra S, Croden FC, et al. A randomized trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2018; 67:1974-83. doi: 10.1136/gutjnl-2017-314968.