Longitudinal Gut Microbiota Changes in Women with Breast Cancer-Related Lymphedema Undergoing a Lifestyle Intervention
10 affiliations
- 1Servicio de Medicina Física y Rehabilitación, Hospital Universitario Virgen de la Victoria, 29010 Malaga, Spain
- 2Department of Medicine and Dermatology, University of Málaga, 29010 Malaga, Spain
- 3Servicio de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, 29010 Malaga, Spain
- 4IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, 29010 Malaga, Spain
- 5Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Malaga, Spain
- 6Instituto de Salud Carlos III, CIBER of Frailty and Healthy Aging (CIBERFES), 28029 Madrid, Spain
- 7Servicio de Medicina Física y Rehabilitación, Hospital Regional Universitario de Málaga, 29010 Malaga, Spain
- 8Unidad de Gestión Clínica de Oncología Médica, Hospital Universitario Virgen de la Victoria, 29010 Malaga, Spain
- 9Department of Surgical Specialties, Biochemistry and Immunology, University of Málaga, 29010 Malaga, Spain
- 10Instituto de Salud Carlos III, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), 28029 Madrid, Spain
Abstract
Breast cancer-related lymphedema (BCRL) is closely associated with obesity, yet the gut microbiota remains poorly characterized in this population. We longitudinally evaluated gut microbiota profiles in 48 women with overweight or obesity and BCRL who were randomized to either a multimodal lifestyle intervention combining an energy-restricted Mediterranean-style diet and exercise (n = 28) or control care (n = 20). Fecal samples collected at baseline, 3 months, and 6 months (144 samples) underwent 16S rRNA gene sequencing. The intervention resulted in greater reductions in body weight, body mass index, and fat mass over time (group × time p < 0.001, p = 0.001, and p = 0.002, respectively). No significant group × time interaction was observed for alpha diversity or overall microbial community composition based on Bray–Curtis dissimilarity (PERMANOVA R2 = 0.006, F = 0.459, p = 0.324). Exploratory DESeq2 differential abundance analyses identified FDR-significant taxon-specific differences, including higher abundances of Barnesiellaceae and Desulfovibrionaceae in the intervention group and of Prevotella_7 and Lachnospiraceae_UCG_010 in controls (FDR-adjusted p < 0.05). These DESeq2 findings were not confirmed in mixed-effects sensitivity analyses after FDR correction. Prevotella_7 was more abundant in controls at baseline and at 6 months. Participant-blocked group × time models, which were given inferential priority, yielded FDR-significant baseline-to-3-month interaction tests for Izemoplasmatales and Frisingicoccus, although the corresponding shrunken effect estimates were close to zero. Secondary, hypothesis-generating analyses based on supplementation status, supplement adherence, and clinically relevant weight-loss response identified additional taxon-specific patterns associated with supplementation and adherence, including a tentative species-level association involving Bifidobacterium bifidum among supplemented participants, whereas no significant microbiota differences were observed by weight-loss response. Overall, these findings provide no evidence of broad restructuring of the gut microbial community but identify exploratory taxon-specific signals that warrant confirmation in larger longitudinal studies using strain-resolved and functional approaches.
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BibTeX
@article{ruizmolina2026longitudinal,
title = {{Longitudinal Gut Microbiota Changes in Women with Breast Cancer-Related Lymphedema Undergoing a Lifestyle Intervention}},
author = {Yolanda Ruiz-Molina and Marina Padial and Cristina Rodríguez-Díaz and Sheila González-Salvatierra and María del Mar Martín-Bravo and Isaac Plaza-Andrades and Lucía Aránega-Martín and Francisca Rodríguez-Pacheco and Alejandro Chicharro-Parras and Corina Verónica Sasso and María Isabel Queipo-Ortuño and Gabriel Olveira},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209008},
url = {https://www.mdpi.com/1422-0067/27/20/9008},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal Gut Microbiota Changes in Women with Breast Cancer-Related Lymphedema Undergoing a Lifestyle Intervention
AU - Yolanda Ruiz-Molina
AU - Marina Padial
AU - Cristina Rodríguez-Díaz
AU - Sheila González-Salvatierra
AU - María del Mar Martín-Bravo
AU - Isaac Plaza-Andrades
AU - Lucía Aránega-Martín
AU - Francisca Rodríguez-Pacheco
AU - Alejandro Chicharro-Parras
AU - Corina Verónica Sasso
AU - María Isabel Queipo-Ortuño
AU - Gabriel Olveira
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209008
UR - https://www.mdpi.com/1422-0067/27/20/9008
AB - Breast cancer-related lymphedema (BCRL) is closely associated with obesity, yet the gut microbiota remains poorly characterized in this population. We longitudinally evaluated gut microbiota profiles in 48 women with overweight or obesity and BCRL who were randomized to either a multimodal lifestyle intervention combining an energy-restricted Mediterranean-style diet and exercise (n = 28) or control care (n = 20). Fecal samples collected at baseline, 3 months, and 6 months (144 samples) underwent 16S rRNA gene sequencing. The intervention resulted in greater reductions in body weight, body mass index, and fat mass over time (group × time p < 0.001, p = 0.001, and p = 0.002, respectively). No significant group × time interaction was observed for alpha diversity or overall microbial community composition based on Bray–Curtis dissimilarity (PERMANOVA R2 = 0.006, F = 0.459, p = 0.324). Exploratory DESeq2 differential abundance analyses identified FDR-significant taxon-specific differences, including higher abundances of Barnesiellaceae and Desulfovibrionaceae in the intervention group and of Prevotella_7 and Lachnospiraceae_UCG_010 in controls (FDR-adjusted p < 0.05). These DESeq2 findings were not confirmed in mixed-effects sensitivity analyses after FDR correction. Prevotella_7 was more abundant in controls at baseline and at 6 months. Participant-blocked group × time models, which were given inferential priority, yielded FDR-significant baseline-to-3-month interaction tests for Izemoplasmatales and Frisingicoccus, although the corresponding shrunken effect estimates were close to zero. Secondary, hypothesis-generating analyses based on supplementation status, supplement adherence, and clinically relevant weight-loss response identified additional taxon-specific patterns associated with supplementation and adherence, including a tentative species-level association involving Bifidobacterium bifidum among supplemented participants, whereas no significant microbiota differences were observed by weight-loss response. Overall, these findings provide no evidence of broad restructuring of the gut microbial community but identify exploratory taxon-specific signals that warrant confirmation in larger longitudinal studies using strain-resolved and functional approaches.
SN - 1422-0067
ER -