mSystems., 2020., 5:e00391-20. https:// doi.org/10.1128/mSystems.00391-20.

Key points Modifying the diet is a key target in the prevention and treatment of GDM. Studies have linked diets with greater intakes of fiber, fruits, green leafy vegetables, and protein from nuts and lean animal proteins such as poultry and fish (all characteristic of the Mediterranean diet) associate with reductions in the risk of GDM. Overall, available data suggest a promising role of dietary bioactive compounds in reducing the risk of GDM. What remains to be elucidated is how these compounds impact biomarkers of adiposity, antioxidant vitamin and mineral status, oxidative stress, and inflammation in women who already have GDM. The present review synthesized and described the latest data from observational studies and randomized controlled trials (RCTs) on the effects of dietary bioactive compounds on biomarkers of maternal adiposity, antioxidant vitamin and mineral status, oxidative stress, and inflammation in GDM. Three RCTs supplemented n-3 fatty acids in women with GDM. Jamilian et al. (2020) reported that n-3 fatty acids from flaxseed oil containing alpha-linolenic acid decreased hs-CRP (β = −1.27, p = 0.006) and MDA (β = −0.47, p < 0.001), and increased GSH (β = +116.55, p = 0.006) and total nitrite (β = +5.42, p < 0.001) compared to placebo group. Jamilian et al. (2018) reported that fish oil containing docosapentaenoic acid (DHA) and eicosapentaenoic acid (EPA) decreased hs-CRP by 49% (p = 0.01). Collectively, that n-3 fatty acids reduced hs-CRP and MDA and increased GSH and TAC. The antioxidant effects of n-3 fatty acids were previously demonstrated in adults with hypertriglyceridemia. A 2018 meta-analysis reported decreased biomarkers of inflammation and lipemia in patients with T2DM who ingested n-3 fatty acids, demonstrating that these dietary bioactive compounds may mitigate inflammation. This review found women with GDM consume more energy, carbohydrates, and fats but smaller amounts of antioxidant vitamins and minerals (vitamin E, selenium, and zinc) than healthy pregnant women. This dietary pattern is undesirable because it promotes maternal obesity, oxidative stress, and inflammation. Data also reveal that a pro-inflammatory diet in the year preceding conception is associated with double the risk of GDM compared to a low-inflammatory diet. Women who develop GDM tend to have lower blood levels of n-3 fats. Supplementing n-3 fatty acids, probiotics, synbiotics, and trace elements also enhances blood antioxidant defenses while reducing inflammation, indicated by lower levels of hs-CRP and MDA.

Gao X Chang S Liu S et al.

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.

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.

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Key Points

A balanced intestinal microecology is now considered an important part of health. The gut microbiota is associated with a number of health problems, especially metabolic syndrome, diabetes, and obesity, which are closely related to dietary factors. In recent years, a series of studies reported the effects of n-3 PUFAs or related carriers rich in n-3 PUFAs on the gut microbiota of animals or humans, including healthy volunteers, overweight individuals with metabolic syndrome, breast cancer survivors, mice with alcohol-induced liver injury, obese mice, early-life antibiotic exposure-induced obese mice, rats fed a high-fat diet, individuals with nonalcoholic fatty liver disease, and early-life-stress rats.

Although existing research reports have shown that ALA and ALA-rich diets have significant regulatory effects on related diseases induced by high-fat diets, gut microbes that play a key role in improving high-fat-diet-related diseases need to be identified, and correlation networks between the gut microbiota and multitissue homeostasis need to be established. To this end, 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 a high-fat diet were studied systematically in this study.

Previous studies have reported that ALA-rich carriers show significant lipid-lowering activity, including reducing liver fat accumulation, alleviating liver steatosis, and lowering blood lipid levels. This is basically consistent with findings here. In addition, the results showed that ALA can significantly reduce the average area size of WAT cells in HFD mice. Turicibacter and Parasutterella were the two important genera that were significantly altered by ALA and significantly correlated with parameters of lipid metabolism in this study. It is suggested that Turicibacter and Parasutterella may regulate lipid metabolism in mice fed a high-fat diet. ALA improved hyperlipidemia and WAT homeostasis in HFD mice, attenuated HFD-induced metabolic endotoxemia and systemic and multitissue inflammation, altered the gut microbial community structure and composition of HFD mice, and remodeled intestinal homeostasis. The  inhibitory effect of ALA on LPS production in HFD mice found is innovative and significant because the trigger factor for ALA to improve inflammation and intestinal barrier-related indicators in HFD mice may be the reduced LPS (outer membrane component of Gram-negative bacteria). Correlation analysis results show that Rikenellaceae_RC9_gut_groupBurkholderiaceae (the family of the genus Parasutterella), Turicibacter, and Bilophila were significantly altered by ALA and correlated with parameters of metabolic endotoxemia and systemic and hepatic inflammation. It is worth mentioning again that Turicibacter was the only genus that was significantly and negatively related to LPS. Rikenellaceae_RC9_gut_groupParasutterellaTuricibacter, and Bilophila may play more important roles in the process of ALA-improved multitissue homeostasis in HFD mice, while other taxa might play a synergistic role with these four genera in various ways. This potential synergy may be systemic evidence that ALA improves multitissue homeostasis in HFD mice by reducing metabolic endotoxemia. Many previous reports can help us to prove that these taxa have such functions, and many other studies have also reported the potential correlation between these taxa and core host parameters.

In summary, the influence of ALA monomers on HFD-induced obesity-related host parameters and the gut microbiota. It was found that ALA could significantly improve HFD-induced multitissue homeostasis. Meanwhile, the established correlation networks between the gut microbiota and multitissue homeostasis in HFD mice lay a foundation for further clarifying the relationship between the gut microbiota and host metabolism, which will be a good model of the “gut-derived doctrine of chronic diseases.”