The Transplantation of ω3 PUFA–Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders

Abstract

Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.

Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

“…EPA ethyl ester supplementation does not modify the composition of the gut microbiome relative to mice on a high fat diet. Previous studies suggest that mixtures of EPA/DHA promote specific compositional changes in the microbiome in a manner that supports lower systemic inflammation associated with insulin resistance [29][30][31] . Therefore, we conducted a microbiome study with control, high fat, and high fat + EPA ethyl ester diets.…”

“…More importantly, EPA did not improve changes in the gut microbiota induced by a high fat diet. Some studies show that n-3 PUFA-enriched fish oils or fat-1 transgenic mice remodel the gut microbiome to lower the abundance of Gram negative bacteria [29][30][31] . EPA ethyl esters are clearly remodeling several lipid pools (as the metabolomics data show), which may in turn influence metabolites generated by the gut microbiome.…”

“…Subsequently, we investigated if EPA ethyl esters remodel the composition of the gut microbiome. The rationale for microbiome 5 studies was driven by evidence that EPA/DHA-enriched fish oils change the composition of gut bacteria to lower systemic inflammation and decrease endotoxemia, a driver of metabolic complications such as insulin resistance [29][30][31] . Parallel hypothesis-generating metabolomic experiments were conducted to identify targets of EPA ethyl esters.…”

Eicosapentaenoic and Docosahexaenoic Acids Differentially Alter Gut Microbiome and Reverse High‐Fat Diet–Induced Insulin Resistance

“…[ 23 ] Fat‐1 transgenic mice that endogenously convert n‐6 to n‐3 PUFAs had higher levels of Tenericutes, Akkermansia , and S24‐7 but less abundant Ruminococcus compared with wild‐type mice. [ 41 ] Here, we comprehensively assessed the individual effect of dietary n‐3 PUFAs on the microbiome in male and female DIO mice and revealed the similarities and differences between DHA and EPA. Notably, we found that EPA and DHA consistently favored the growth of Lactobacillus which has been evidenced to improve gut integrity, endotoxemia, and inflammation [ 42,43 ] as well as SCFA‐producing species from Lachnospiraceae [ 44 ] in both male and female DIO mice.…”

The gut microbiota at the intersection of diet and human health

“…These metabolic disturbances were accompanied by reductions in phylogenetic diversity in the saturated fat-fed mice, and receipt of transplanted microbiota from mice fed fish oil abrogated saturated fat-induced inflammation (31). Furthermore, transgenic mice that constitutively produce w3 polyunsaturated fatty acids possess a microbiome with enhanced phylogenetic diversity that offers protection against the metabolic consequences of a high-saturated-fat, high-sugar diet (32).…”