Over 30 million people report the use of fish oil supplements in the United States, where dietary fish intake remains low. Prescription fish oil is approved to treat high triglycerides; however, there is increasing evidence that consumption of fish oil may be beneficial for other diseases, such as cardiovascular and autoimmune diseases. It is generally accepted that these potential health benefits stem from omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) found in fish oil. n-3 LCPUFAs, notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter immune function and are proposed to be beneficial against chronic inflammatory conditions; however, observations across multiple models of pathogen-exposed animals suggest deleterious immunosuppression due to fish oil. The majority of research on fish oil and the immune system has focused primarily on T cells, monocytes, and dendritic cells of the immune system. However, the extent to which fish oil alters the function of B cells, a vital component of humoral immunity, remains relatively uninvestigated. Previous research demonstrated that DHA-enriched fish oil (DFO) exacerbated Helicobacter hepaticus-induced colitis in SMAD3-/- mice. Given the aberrant response to H. hepaticus in DFO-fed SMAD3-/- mice, it was hypothesized that fish oils alter humoral immunity, specifically B cell function. To test this hypothesis, SMAD3-/- mice were fed either control or various dietary fish oils, including non-enriched (e.g., menhaden oil [MO]) and enriched (e.g., EPA- or DHA-enriched) fish oils, and then assessed for B cell development and function. The results indicate that the n-3 LCPUFA composition of fish oil mediates observed B cell immunological outcomes. All dietary treatments were found to markedly increase n-3 LCPUFAs and decrease n-6 LCPUFAs of red blood cell (RBC) and B cell phospholipid fatty acid profiles. B cells from SMAD3-/- mice fed MO and DFO dietary treatments share a number of mechanistic and immunological outcomes, such as decreased clustering of membrane microdomains concomitant with increased cytokine production in response to ex vivo stimulation. In contrast, EPA-enriched fish oil (EFO) had increased microdomain clustering, decreased expression of B cell surface markers, and ex vivo function. The n-3 LCPUFA composition of B cells was tightly correlated to RBCs phospholipid fatty acids, a common biomarker of n-3 LCPUFA exposure; however, it is unclear how levels of n-3 LCPUFAs in the blood relate to levels of n-3 LCPUFAs in other tissues, which may be more prognostic of health benefit at the tissue-level. This prompted the characterization of the phospholipid fatty acid profile of blood and gastrointestinal (GI) tissues, of colitis-prone, SMAD3-/- fed increasing amounts of EPA+DHA. Levels of EPA+DHA were chosen to mirror recommended intakes of n-3 LCPUFAs in humans. RBCs were highly correlated to the n-3 and n-6 LCPUFAs of all other GI; however, the absolute levels of n-3 and n-6 LCPUFAs varied considerably between blood and tissue. These findings confirm a novel role for B cell immunomodulation by dietary fish oil and provide further evidence that RBCs serve as a adequate, surrogate biomarker for n-3 LCPUFA incorporation. As an increasing popular dietary supplement, understanding the mechanistic and functional outcomes of fish oil consumption provide a foundation for research of more targeted fish oil therapeutics.
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