Correlations between α-Linolenic Acid-Improved Multitissue Homeostasis and Gut Microbiota in Mice Fed a High-Fat Diet

Abstract

Previous studies have shown that α-linolenic acid (ALA) has a significant regulatory effect on related disorders induced by high-fat diets (HFDs), but little is known regarding the correlation between the gut microbiota and disease-related multitissue homeostasis. We systematically investigated the effects of ALA on the body composition, glucose homeostasis, hyperlipidemia, metabolic endotoxemia and systemic inflammation, white adipose tissue (WAT) homeostasis, liver homeostasis, intestinal homeostasis, and gut microbiota of mice fed an HFD (HFD mice). We found that ALA improved HFD-induced multitissue metabolic disorders and gut microbiota disorders to various degrees. Importantly, we established a complex but clear network between the gut microbiota and host parameters. Several specific differential bacteria were significantly associated with improved host parameters. Rikenellaceae_RC9_gut_group and Parasutterella were positively correlated with HFD-induced “harmful indicators” and negatively correlated with “beneficial indicators.” Intriguingly, Bilophila showed a strong negative correlation with HFD-induced multitissue metabolic disorders and a significant positive correlation with most beneficial indicators, which is different from its previous characterization as a “potentially harmful genus.” Turicibacter might be the key beneficial bacterium for ALA-improved metabolic endotoxemia, while Blautia might play an important role in ALA-improved gut barrier integrity and anti-inflammatory effects. The results suggested that the gut microbiota, especially some specific bacteria, played an important role in the process of ALA-improved multitissue homeostasis in HFD mice, and different bacteria might have different divisions of regulation. IMPORTANCE Insufficient intake of n-3 polyunsaturated fatty acids is an important issue in modern Western-style diets. A large amount of evidence now suggests that a balanced intestinal microecology is considered an important part of health. Our results show that α-linolenic acid administration significantly improved the host metabolic phenotype and gut microbiota of mice fed a high-fat diet, and there was a correlation between the improved gut microbiota and metabolic phenotype. Some specific bacteria may play a unique regulatory role. Here, we have established correlation networks between gut microbiota and multitissue homeostasis, which may provide a new basis for further elucidating the relationship between the gut microbiota and host metabolism.

Construction of a “Bacteria-Metabolites” Co-Expression Network to Clarify the Anti–Ulcerative Colitis Effect of Flavonoids of Sophora flavescens Aiton by Regulating the “Host–Microbe” Interaction

“…It is an omega-3 unsaturated fatty acid with anti-inflammatory and antioxidant effects ( Kim et al, 2014 ), and is reported to be significantly negatively correlated with the Rikenellaceae_RC9_gut_group. It is worth noting that the Rikenellaceae_RC9_gut_group affects the intestinal permeability and oxidative stress and is positively correlated with the lipopolysaccharide in the serum; it has also been reported to be negatively correlated with IL-10 in the colon ( Gao et al, 2020 ). PICRUSt analysis showed that the arachidonic acid and fatty acid synthesis pathways were enriched in the UC mice, indicating that the UC mice had increased lipid metabolism, which might be related to the upregulation of inflammation-related bacteria, such as in Enterobacteriaceae and Proteobacteria ( Tang et al, 2020 ).…”

Alpha‐linolenic acid regulates the gut microbiota and the inflammatory environment in a mouse model of endometriosis

“…The supplementation of flaxseed oil rich in ALA can help prevent endotoxemia 44 . Evidence shows that ALA can inhibit the production of LPS in HFD mice 45 . In vitro studies have shown that ALA can inhibit the inflammatory characteristics of typically activated macrophages in human THP‐1 cells induced by LPS and reduce the production of IL‐1β, IL‐6, TNF‐α and PGD2 46 .…”

Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery

“…Roseburia can affect colonic motility, immunity maintenance, and anti-inflammatory properties ( Tamanai-Shacoori et al, 2017 ). Therefore, the anaerobes and health-associated microbiota are not only important in maintaining gut barrier integrity, anti-inflammatory effects, and immune balance but also play a key role in maintaining a positive microbial environment in the gut ( Bian et al, 2020 ; Gao et al, 2020 ; Jiang et al, 2020 ; Seo et al, 2020 ), and their depletion may be a potential inducement of elevated postoperative systemic and gut local inflammation.…”