Differential Effects of DHA-Rich Fish Oil Supplementation on Intestinal and Pulmonary Alterations in Experimental Malaria Caused by <i>Plasmodium berghei</i> NK65

Malaria infection can trigger Acute Respiratory Distress Syndrome (ARDS), a potentially lethal complication resulting, among other factors, from an exacerbated inflammatory response associated with the infection. In addition, the disease appears to impact the intestinal tract, causing disorders that in turn can influence the severity of lung damage due to bidirectional communication between these organs, known as the gut-lung axis. DHA-rich fish oil (omega-3) has been demonstrated to mitigate lung inflammation in mice infected with Plasmodium berghei ANKA, a highly virulent parasite strain. However, it remains unclear whether this effect extends to any species or strain of Plasmodium. Therefore, in this study, the potential of DHA-rich fish oil to modulate lung injury was evaluated during the experimental infection of C57BL/6 mice infected with P. berghei NK65. In addition, we also analyzed the effect of supplementation on the intestinal environment. Although DHA-rich fish oil supplementation was associated with partial preservation of intestinal morphology, including reduced intestinal shortening, these effects did not translate into improved pulmonary outcomes. These findings highlight the strain- and pathogenesis-dependent effects of ω-3 supplementation, emphasizing distinct responses across different infection models. Specifically, our results reinforce the importance of considering the diversity of pathogenic profiles among Plasmodium strains in the investigation of nutritional or immunomodulatory interventions.