A Paternal Fish Oil Diet Preconception Modulates the Gut Microbiome and Attenuates Necrotizing Enterocolitis in Neonatal Mice

Abstract

Epidemiology and animal studies suggest that a paternal history of toxicant exposure contributes to the developmental origins of health and disease. Using a mouse model, our laboratory previously reported that a paternal history of in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased his offspring’s risk of developing necrotizing enterocolitis (NEC). Additionally, our group and others have found that formula supplementation also increases the risk of NEC in both humans and mice. Our murine studies revealed that intervening with a paternal fish oil diet preconception eliminated the TCDD-associated outcomes that are risk factors for NEC (e.g., intrauterine growth restriction, delayed postnatal growth, and preterm birth). However, the efficacy of a paternal fish oil diet in eliminating the risk of disease development in his offspring was not investigated. Herein, reproductive-age male mice exposed to TCDD in utero were weaned to a standard or fish oil diet for one full cycle of spermatogenesis, then mated to age-matched unexposed females. Their offspring were randomized to a strict maternal milk diet or a supplemental formula diet from postnatal days 7–10. Offspring colon contents and intestines were collected to determine the onset of gut dysbiosis and NEC. We found that a paternal fish oil diet preconception reduced his offspring’s risk of toxicant-driven NEC, which was associated with a decrease in the relative abundance of the Firmicutes phylum, but an increase in the relative abundance of the Negativicutes class.

Paternal preconceptional supplementation of n‐3 polyunsaturated fatty acids alleviates offspring nonalcoholic fatty liver disease in high‐fat diet‐induced obese mice

“…Recently, a reduction in offspring's risk of toxicant-driven necrotizing enterocolitis has been found by a paternal fish oil diet in preconception, with a decrease in relative abundance of the Firmicutes phylum, and an increase in relative abundance of the Negativicutes class (Rumph et al, 2022).…”

“…Our findings, presented herein, demonstrated that the microbial compositions were altered by paternal n‐3 PUFAs in the offspring of F1 and F2 generations, and that the existed correlation between the altered abundance of bacteria and the hepatic expression of genes associated with lipogenesis, fat oxidation, inflammation, or fibrosis, indicating the beneficial effects of the altered offspring gut microbiota by paternal n‐3 PUFAs on offspring NAFLD development. Recently, a reduction in offspring's risk of toxicant‐driven necrotizing enterocolitis has been found by a paternal fish oil diet in preconception, with a decrease in relative abundance of the Firmicutes phylum, and an increase in relative abundance of the Negativicutes class (Rumph et al., 2022).…”

Paternal effects on fetal programming

“…A recent mouse-based study reported that fish oil feeding to male mice for one spermatogenic cycle before breeding resulted in a reduction in lung inflammation and expression of pulmonary pro-inflammatory cytokines in pups ( Rumph et al, 2023 ). These authors also observed that offspring mice born from sires fed fish oil during spermatogenesis had distinct gut microbiota compared to that of offspring born from control sires, demonstrating the influence of paternal diet on offspring early life microbial colonization ( Rumph et al, 2022 ).…”