Exploring the Interplay Between Gut Microbiota and the Melatonergic Pathway in Hormone Receptor-Positive Breast...

Area of Science:

• Microbiology
• Endocrinology
• Oncology

Background:

• Emerging evidence suggests a link between gut microbiota, melatonin, and hormone receptor-positive breast cancer (HR+ BC).
• The interplay between gut dysbiosis, melatonin synthesis, and cancer development warrants further investigation.

Purpose of the Study:

• To investigate alterations in gut microbiota, the serotonin-N-acetylserotonin (NAS)-melatonin axis, fecal metabolites, and intestinal permeability in HR+ BC patients compared to controls.
• To explore potential correlations between gut microbiota composition and the measured biochemical markers.

Main Methods:

• Analysis of gut microbiota composition using 16S rRNA sequencing.
• Quantification of serotonin, NAS, melatonin, and short-chain fatty acids (SCFAs) via mass spectrometry.
• Measurement of beta-glucuronidase (βGD) activity, zonulin, and melatonin-synthesizing enzymes (AANAT, ASMT) using ELISA and fluorometric assays.

Main Results:

• HR+ BC patients showed gut dysbiosis with reduced *Bifidobacterium longum* and increased *Bacteroides eggerthii*.
• Elevated fecal βGD activity, SCFA levels, and serum zonulin indicated increased intestinal permeability in BC patients.
• BC patients had higher serum serotonin and NAS, lower melatonin, increased AANAT, and decreased ASMT, resulting in a higher NAS/melatonin ratio.

Conclusions:

• Gut microbiota alterations, disrupted melatonin synthesis, and increased intestinal permeability may contribute to HR+ BC pathophysiology.
• *Bifidobacterium longum* showed a negative correlation with βGD activity, while *Bacteroides eggerthii* correlated positively.
• The NAS/melatonin ratio may serve as a potential biomarker for HR+ BC, requiring further mechanistic studies.