Dietary fish oil improves intestinal barrier function and intestinal microbiota composition and reduces systemic inflammation in a mouse model of moderate acute malnutrition

Acute malnutrition (wasting) remains a global public health problem. Ready-to-use therapeutic foods (RUTF) and supplemental foods (RUSF) for treatment of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM), respectively, come in the form of macro- and micronutrient-dense pastes. These lipid-dense treatments provide the energy and nutrients needed to support growth but have significant rates of relapse. Their role in reversing pathophysiological contributors to malnutrition, such as intestinal barrier dysfunction, intestinal dysbiosis, and systemic inflammation have not been evaluated. Traditional lipid-dense RUTFs and RUSFs are rich in pro-inflammatory omega-6 polyunsaturated fatty acids (PUFAs) but low in anti-inflammatory omega-3 PUFAs, which could fuel malnutrition-related pathological inflammation. We reasoned that reduced dietary omega-6 (n-6) PUFAs and increased dietary long-chain omega-3 (n-3) PUFAs found in fish oil would reduce malnutrition-related pathological inflammation. In an established mouse model of MAM, we observed that altering the dietary n-3/n-6 PUFA ratio through replacing dietary corn oil with fish oil improved the diversity and composition of the caecal microbiota, improved intestinal mucosal barrier and immune defence, reduced translocation of bacteria and bacterial lipopolysaccharides (LPS), and dampened systemic inflammation. Furthermore, dietary fish oil protected against weight loss upon systemic challenge with bacterial LPS. The anti-inflammatory effects of dietary fish oil did not compromise host defence against challenge with the intestinal pathogen, Citrobacter rodentium. Collectively, these results suggest that dietary fish oil blunts inflammation that contributes to the pathogenesis of MAM. Inclusion of fish oil in dietary interventions may be beneficial in prevention or reduction of malnutrition-associated inflammation.