Western diet accelerates endometriosis growth and disrupts gut health

Accelerated lesion growth and key gut bacteria loss link the Western diet to heightened endometriosis risk, opening new discussions on diet as a potential intervention.

A recent study in the journal BMC Medicine examines the effects of a Western diet on the development of endometriotic lesions in mice.

Endometriosis and the gut microbiome

The Western diet (WD) not only promotes lesion growth but also activates specific macrophage markers (CD80 and CD206), enhancing inflammation and potentially accelerating endometriotic lesion progression.

Despite being a benign condition, endometriosis causes significant morbidity in affected women, 10% of whom are of reproductive age. Endometriosis is characterized by the abnormal growth of tissues resembling that of the uterine lining or endometrium outside of the uterine cavity.

Women with advanced endometriosis exhibit gut microbial changes. Previous studies have reported that anti-inflammatory diets may relieve endometriosis-associated pain, which may be achieved by altering bacterial and gut metabolism.

The gut microbiome can influence the development of innate immunity and inflammation. In particular, bacterial components or byproducts may inhibit or activate macrophage memory responses. This phenomenon, termed trained immunity, helps these cells respond faster with a stronger inflammatory response.

About the study

After four weeks, endometriotic tissue was surgically implanted in female mice, following which the development of endometriotic lesions was monitored by ultrasound. Mice consumed either a control or Western diet (WD) that typically contains more fat and less fiber. Notably, a high-fat diet was avoided to prevent changes due to obesity or overweight.

At seven weeks, mice were sacrificed. Both the characteristics of the lesions and the composition of the gut microbiome were analyzed.

Western diet promotes lesion growth

Immune-inflammatory changes and WD

Despite unchanged inflammatory markers, lesions in the WD group were more likely to be fibrotic and exhibit proliferation. Macrophages were also more active in the WD group lesions despite the same proportion of immune cells present in the lesions in both groups.

The increased lesion size with the WD may reflect WD-linked trained immunity, like that induced by the Bacillus Calmette-Guérin (BCG). Although not discussed in the current study, macrophage polarization may be driven by increased gram-positive bacilli in the gut, similar to the effect produced by BCG.

Metabolic differences with WD

Serum glucose levels were reduced in mice with endometriosis as compared to the original endometriosis-free mice before they became recipients of uterine tissue implants, perhaps reflecting higher glucose consumption.

Both WD and endometriosis independently shift gut microbiota composition in mice, showing distinct differences from control diets even without visible dysbiosis (altered Firmicutes/Bacteroidetes ratios), underscoring the microbiota’s nuanced role in endometriosis.

WD mice with endometriosis produced more lactate during the anaerobic glucose metabolism than non-endometriotic WD mice; however, no significant differences were observed in the controls. The higher levels of glucose oxidation may be diet-related and due to activation of the leptin pathway proteins, which lowers glucose levels, thus indicating that leptins are involved in endometriotic lesion development.

Many women with endometriosis have functional bowel disorders like irritable bowel syndrome, which dietary changes might alleviate. Some studies suggest that endometriotic lesions are reduced in size after probiotic administration; however, the specific metabolic changes remain unknown.

WD causes the intestinal epithelial barrier to fail, allowing toxic byproducts of bacterial metabolism to enter the host bloodstream. This subsequently induces chronic low-grade inflammation, which is also present in endometriosis.

Gut microbe changes and WD

Gut microbiome changes were significantly correlated with differences in the dietary pattern. However, after the onset of endometriosis in both groups, gut microbiota in WD mice with the largest lesions was deficient in Akkermansia muciniphila. Despite this, there was no evidence of gut dysbiosis in terms of disrupted Firmicutes/Bacteroidetes ratio.

A. muciniphila is less abundant in metabolic syndrome and inflammatory bowel disorders like Crohn’s. However, A.muciniphila supplementation as a probiotic reduces low-grade inflammation and promotes intestinal wall integrity. Despite normal counts in WD mice, the induction of endometriosis was associated with a total depletion of A.muciniphila, thus emphasizing its possible protective function.

Endometriosis causes changes in the gut microbiota, with certain alterations in the gut microbial environment promoting lesion progression. Although intestinal dysbiosis was not observed in the current study, other animal and human studies suggest it is present in endometriotic hosts.

Conclusions

Endometriotic lesions in a mouse model were significantly larger and progressed faster in mice consuming a Western diet. Thus, dietary choices appear to influence the course of endometriosis and, as a result, can be targeted to mitigate symptoms associated with this disease.

Future studies should identify the optimal dietary pattern in endometriosis patients and whether unhealthy changes linked to poor dietary patterns are reversible. The reasons for the acute depletion of A. muciniphila should also be investigated.

Journal reference:

• Parpex, G., Chassaing, B., Bourdon, M., et al. (2024). Western diet promotes endometriotic lesion growth in mice and induces depletion of Akkermansia muciniphila in intestinal microbiota. BMC Medicine. doi:10.1186/s12916-024-03738-9.