Longitudinal Effects of Dietary Oxidized Lipids on the Gut Microbiome and Mycobiome in Pigs

Abstract

Gut microbial communities are modulated by host and environmental factors such as genetics, disease state, xenobiotics and diet. Western high fat diets are known to induce dysbiosis of the microbiome and are associated with chronic diseases – such as obesity and type 2 diabetes – but the effects of dietary lipid oxidation products (LOPs) on the gut microbial communities are unknown. Primary and secondary LOPs are abundant in western diets due to the extensive use of oxidation‐susceptible fats such as unsaturated fats and food processing methods such as deep fat frying that generate them. In this study, we utilized pigs as a translational model to elucidate whether a high fat diet containing high levels of LOPs would differentially alter the microbiome, mycobiome and host phenotype. We hypothesized that a high fat diet containing LOPs will cause selective alteration of gut microbiome and mycobiome compared to high fat diet alone (i.e., with low amounts of LOPs). We randomized twenty‐one day old pigs (N=48) to the following dietary regimens for five months: (1) Low‐fat diet (Control, 9% calories from fat); (2) High‐fat diet (HF, 44% calories from fat); (3) High‐fat with high amounts of LOPs (HF+LOP, ~44% calories from fat. Fecal samples for bacterial and fungal sequencing by Illumina were obtained from the pigs 2 and 5 months after they were placed on the above dietary regimen. The three groups of pigs initially exhibited similar microbiome alpha diversity (Shannon diversity index), but the groups receiving high‐fat diets (HF and HF+LOPs) showed reductions in diversity by the end point. Diet containing LOPs produced the lowest diversity by the endpoint. The HF diet elevated the phyla Firmicutes and decreased phyla Bacteroidetes compared to control diet. Compared to control diet, both HF diets increased Clostridiaceae and Turicibacteraceae, while the presence of LOPs induced a bloom in Enterobacteriaceae. The effect of LOPs was further explored using the binomial analysis DESeq2, revealing that Enterbacteriaceae, Epulopiscium, Elusimicrobiaceae, and Lactobacillus were significantly increased (when compared to HF alone, following FDR correction). The mycobiome of all the animals was dominated by the genus Kazachstania, a known porcine yeast. Pigs on the HF diets showed significantly lower levels of Aspergillus, Penicillium, Oidiodendron, and Wallemia when compared to those on control diet. The presence of LOPs in the diet led to significant elevation of fungi Schwanniomyces (compared to HF diet alone). Here, for the first time, we demonstrate that dietary LOPs can alter the bacterial and fungal communities in the gut, even when controlling for total dietary fat intake. These findings suggest that the oxidation state of dietary lipids is an important factor to consider when studying the effects of western diets on chronic disease risk.Support or Funding InformationThe research was supported by the Biomedical & Genomic Research Group Discretionary Fund, University of Wisconsin‐Madison.