Get started
Work

Tamoxifen Promotes Sustained Bifidobacterium Enrichment in the Gut Microbiota of Male and Female Rats After Spinal Cord Injury

Year: 2026
Type: article
Abstract: Spinal cord injury (SCI) triggers complex secondary injury cascades that limit neurological recovery. Tamoxifen (TAM), a selective estrogen receptor modulator, exerts neuroprotective effects in experimental SCI, although its underlying mechanisms remain unknown. Given the emerging role of gut microbiota dysregulation in SCI, we investigated whether TAM-associated recovery is accompanied by alterations in gut microbial composition and predicted function. We conducted a longitudinal, sex-inclusive analysis of 61 Sprague–Dawley rats of both sexes assigned to naïve (NAÏVE), sham-placebo (SHAM PLB), sham-TAM (SHAM TAM), injured-placebo (INJ PLB), or injured-TAM (INJ TAM) groups. Injured animals received a moderate T10 contusion followed by a 21-day TAM (0.71 mg/day) or placebo pellet, and fecal samples were collected at 0, 7, 14, 21, and 28 days post-injury. Fecal samples were analyzed by 16S rRNA gene sequencing. Results showed that TAM induced sustained shifts in microbial community composition, with treatment-associated divergence emerging at 14 days post-injury (DPI) in females and 21 DPI in males. Bifidobacterium exhibited the most consistent TAM-associated enrichment across sexes. Bifidobacterium abundance was negatively associated with recovery in INJ PLB animals and positively associated with INJ TAM animals; because behavioral and microbiome measurements were not made in the same animals, these associations are hypothesis-generating only. PICRUSt2 analysis revealed TAM-associated changes in predicted microbial function, including increased glycogen degradation pathways from 14 DPI onward in both sexes. Together, these findings identify sustained TAM-associated taxonomic and predicted functional remodeling of the gut microbiota following SCI.
DOI: 10.3390/ijms27198729
Authors: Luis H. Pagán-Rivera, Filipa Godoy-Vitorino, Samuel E. Ocasio-Rivera, Maria E. Santiago-Gascot, Viviana González, José M. Santiago, Iris Salgado, Aranza Torrado-Tapias, Jennifer M. Colón-Mercado, Carolina García-Guay, Jorge D. Miranda
Institutions: University of Puerto Rico, Medical Sciences Campus, University of Puerto Rico at Carolina, Central University of the Caribbean, National Institutes of Health, National Human Genome Research Institute, University of Puerto Rico at Río Piedras
Language: English
Open Access status: gold
Estimated APC paid: $3,499
Awards: Neuroscience Research Opportunities to Increase Diversity (NeuroID), Puerto Rico Center for Microbiome Sciences, Advancing Competitive Biomedical Research in Puerto Rico, COBRE PHASE III: Center for Neuroplasticity at the University of Puerto Rico, Center for Collaborative Research in Health Disparities, Effects of Tamoxifen in skeletal muscle recovery after spinal cord injury and mechanisms activated by the drug
OpenAlex ID: W7214735000
FWCI:
Cites: 70
Cited by:
Related to: 10