Mahno, Noor Ezmas and Ahmad, Hajar Fauzan and Termizi, Sahrol Azmi
(2026)
Multi-kingdom gut microbiome features associated with breast cancer and menopausal status.
Gut Microbiology, 2.
pp. 1-12.
ISSN 3051-1720
Abstract
Rising breast cancer incidences signal a growing need to improve understanding of its formation. This study
explores the multi-kingdom link between the gut microbiome, short-chain fatty acids (SCFAs), and breast cancer
risk, with a focus on menopausal status. Recently diagnosed breast cancer patients (n=32) and age-matched
controls (n=32) were recruited for a case-control study. 16S rRNA and ITS1 amplicon sequencing, along with
stool metabolome analysis, were conducted. Stratification by menopausal status revealed Holdemanella and
unclassified Aureobasidiaceae were most prominent in postmenopausal cancer patients. Significant differences in
beta-diversity were observed for both bacterial (p = 0.007) and fungal (p = 0.004) communities across groups.
Within breast cancer patients, Spearman rank analysis identified Holdemanella as a central hub, significantly
correlating with fungal genera Rhizopus (p = 0.009) and Malassezia (p = 0.010). Despite not reaching statistical
significance (p > 0.05), the consistent pattern of increased propanoic acid and reduced butanoic acid suggests a
meaningful shift in microbial metabolic activity rather than random variation. This is further supported by the
predicted upregulation of β-galactosidase and β-glucosidase, indicating active functional changes within the
microbiome pointing to estrobolome activities. This study identifies Holdemanella, Aspergillus, and unclassified
Aureobasidiaceae as potential biomarkers and highlights the unique microbial signatures associated with breast
cancer.
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