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.

Scope: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of 𝜶-linolenic acid (ALA) has seldom been reported. Methods and Results: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg −1 ) promotes small intestinal and villus growth by activating the Wnt/𝜷-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. Conclusion: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/𝜷-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.

Mol. Nutr. Food Res. 2022, 66, 202100408 DOI: https://doi.org/10.1002/mnfr.202100408 Dietary nutrition has the effect of regulating the activity of intestinal stem cells (ISCs), however, the regulation effect of α‐linolenic acid (ALA) has seldom been reported. In article number 2100408, Jun Sheng and co‐workers observe SCFAs produced by Ruminococcaceae mediates ALA promote ISCs proliferation by activating Wnt/β‐catenin signaling pathway and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.