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

Abstract

Problem This study aims to investigate the effects of alpha‐linolenic acid (ALA) on the gut microbiota (GM) and the abdominal environment in mice with endometriosis (EMS). Methods The effects of faecal microbiota transplantation (FMT) from EMS mice on mice treated with antibiotic cocktail were conducted. The 16S rRNA sequencing and PICRUSt software were used to detect the structure and function of GM respectively. The protein levels of Claudin 4 and ZO‐2 in the intestinal wall were detected using the western blotting. The level of LPS in the abdominal cavity was detected using enzyme‐linked immunosorbent assay (ELISA). The content of macrophages in the abdominal cavity was detected using flow cytometry. Results The exogenous supplementation of ALA could restore the abundance of Firmicutes and Bacteroidota in EMS mice. After the ALA treatment, the abundance of 125 functional pathways and 50 abnormal enzymes related to GM in EMS mice was significantly improved (p < .05). The expression of the ZO‐2 protein in the intestinal wall was decreased, and the level of LPS in the abdominal cavity was significantly increased after FMT from EMS mice (p < .05). ALA could increase the expression of the ZO‐2 protein in the intestinal wall of EMS mice, reduce the level of LPS in the abdominal cavity (p < .05) and reduce the aggregation of peritoneal macrophages (p < .05). Conclusion Alpha‐linolenic acid can improve the GM, intestinal wall barrier and abdominal inflammatory environment and reduce the level of LPS in mice with EMS.

Huayu Jiedu Fang Protects Ovarian Function in Mouse with Endometriosis Iron Overload by Inhibiting Ferroptosis

“…EM model mice were prepared according to a previously published study [ 16 ]. Every C57 mouse was injected with 0.2 mL of estradiol solution subcutaneously on the back of the neck three times at a frequency of one injection per 4 days.…”

Influence of the gut microbiota on endometriosis: Potential role of chenodeoxycholic acid and its derivatives

“…Studies have shown that EMS changes the structure of the GM, causes an imbalance in the F/B ratio, and reduces the α and β diversity ( Ni et al, 1989a ; Ni et al, 1989b ), which are measures of the diversity of the microbiota within a single individual and an indicator to characterize the similarities in microbial composition between individuals, respectively ( Table 1 ). The imbalance in the GM leads to inflammation that damages the health of the intestinal epithelium and affects the health of the whole body through the downstream effects of metabolism.…”

“…Studies have reported that IL-17A plays an important role in EMS progression ( Shi et al, 2022 ). Lactobacillus has long been used as a probiotic supplement to maintain health as well as prevent and treat diseases, but its proportion in GM elevated in EMS models ( Ni et al, 1989b ; Cao et al, 2020 ), which may be due to suppression of the differentiation of Th17 cells by Lactobacillus ( Wilck et al, 2017 ) . Furthermore, we found that the proportion of bifidobacteriaceae was elevated in some reports ( Ni et al, 1989b ; Yuan et al, 2018 ; Shan et al, 2021 ), and a high proportion of bifidobacteriaceae promoted the differentiation of Th17 cells ( Ang et al, 2020 ).…”

“…Lactobacillus has long been used as a probiotic supplement to maintain health as well as prevent and treat diseases, but its proportion in GM elevated in EMS models ( Ni et al, 1989b ; Cao et al, 2020 ), which may be due to suppression of the differentiation of Th17 cells by Lactobacillus ( Wilck et al, 2017 ) . Furthermore, we found that the proportion of bifidobacteriaceae was elevated in some reports ( Ni et al, 1989b ; Yuan et al, 2018 ; Shan et al, 2021 ), and a high proportion of bifidobacteriaceae promoted the differentiation of Th17 cells ( Ang et al, 2020 ). Furthermore, feces from mice with EMS were transplanted into antibiotic gavaged EMS mice which exhibited more severe EMS symptoms, such as an increased number of endometriotic foci ( Chadchan et al, 2021 ).…”

“…The GM has been shown to regulate extraintestinal inflammation ( Karmarkar and Rock, 2013 ). The GM altered by EMS leads to the destruction of the tight junctions of the intestine and decreases the expression of ZO-2 protein, which further increases the permeability of the intestine ( Ni et al, 1989b ), resulting in the translocation and infiltration of a large number of Gram-negative bacteria outside the intestinal cavity ( Meroni et al, 2019 ). LPS can activate macrophage Toll-like receptor 4 (TLR4) in innate immunity, producing large amounts of tumour necrosis factor-α (TNF-α) and interleukin (IL)-8 and promoting the formation of an inflammatory environment ( Figure 1 ) ( Harada et al, 2001 ).…”