{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:35:11Z","timestamp":1791228911195,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Response to neoadjuvant chemotherapy (NAC) varies substantially among breast cancer patients and is only partially explained by tumor-intrinsic factors. The gut microbiome has emerged as a potential modulator of chemotherapy efficacy, yet its role in breast cancer remains underexplored. This study aimed to characterize gut microbial composition, functional potential, and microbially derived metabolites in breast cancer patients undergoing NAC. Methods: baseline stool samples from 39 chemotherapy-na\u00efve breast cancer patients undergoing NAC were analyzed using shotgun metagenomic sequencing and targeted metabolomics. Patients were stratified by pathological complete response (pCR, n = 17; no pCR, n = 22). Microbial taxonomic and functional profiles, short-chain fatty acids (SCFAs) and bile acids were assessed, with subgroup analysis performed in triple-negative breast cancer (TNBC). Results: Patients achieving pCR exhibited significantly higher baseline microbial richness compared to non-responders (p = 0.040). Differential abundance analysis revealed enrichment of Dialister, Kineothrix, and Jutongia in responders, whereas Rothia, Leuconostoc, Klebsiella, Jingyaoa, Cuneatibacter, Youxingia, and Bittarella were enriched in non-responders. SCFAs (acetate, propionate and butyrate) positively correlated with microbial glucose catabolic pathways, while caproate was negatively associated with multiple amino acid, lipid, vitamin, and cell wall biosynthesis pathways, including peptidoglycan maturation. Metabolomic analysis identified higher deoxycholic acid (DCA) levels in non-responders and increased C6 levels in responders, although these associations did not remain significant after multiple testing correction. Similar trends were observed in the TNBC subgroup (n = 15). Conclusions: Baseline gut microbiome diversity, taxonomic composition, and functional metabolic potential are associated with response to neoadjuvant chemotherapy in breast cancer, supporting the gut microbiome and its produced metabolites as a potential biomarker of treatment efficacy.<\/jats:p>","DOI":"10.3390\/diagnostics16030433","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:12:46Z","timestamp":1770041566000},"page":"433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Baseline Gut Microbiome and Metabolite Profiles Associate with Treatment Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1583-9927","authenticated-orcid":false,"given":"Elza Elizabete","family":"Liepina","sequence":"first","affiliation":[{"name":"Institute of Oncology and Molecular Genetics, Riga Stradins University, Pilsonu Street 13, Block 13, LV-1002 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5122-8679","authenticated-orcid":false,"given":"Elina","family":"Sivina","sequence":"additional","affiliation":[{"name":"Institute of Oncology and Molecular Genetics, Riga Stradins University, Pilsonu Street 13, Block 13, LV-1002 Riga, Latvia"},{"name":"Solid Tumor Systemic Treatment Clinic, Riga East University Hospital, Hipokrata Street 4, LV-1079 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lelde","family":"Jurkane","sequence":"additional","affiliation":[{"name":"Institute of Oncology and Molecular Genetics, Riga Stradins University, Pilsonu Street 13, Block 13, LV-1002 Riga, Latvia"},{"name":"Clinic of Oncology, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV-1002 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-2973","authenticated-orcid":false,"given":"Zanda","family":"Daneberga","sequence":"additional","affiliation":[{"name":"Institute of Oncology and Molecular Genetics, Riga Stradins University, Pilsonu Street 13, Block 13, LV-1002 Riga, Latvia"},{"name":"Department of Biology and Microbiology, Riga Stradins University, Dzirciema Street 16, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","unstructured":"(2025, December 18). 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