{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T03:48:26Z","timestamp":1768276106951,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation (SNF)","doi-asserted-by":"publisher","award":["33IC30_166844"],"award-info":[{"award-number":["33IC30_166844"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Litwin Foundation (New Hyde Park, NY, USA)","award":["33IC30_166844"],"award-info":[{"award-number":["33IC30_166844"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Anthocyanins (ACs) have been shown to elicit anti-inflammatory and antioxidant effects in animal models of ulcerative colitis (UC). Furthermore, we previously observed in a double-blind randomized trial in UC patients that biochemical disease activity tended to be lower in patients that were exposed to AC. Here, we report on the changes in the fecal microbiome composition in these patients upon AC exposure. UC patients received a 3 g daily dose of an AC-rich bilberry extract (ACRE) for eight weeks. We determined the microbiome composition in longitudinal stool samples from 24 patients and quantified the degree of change over time. We also correlated the relative abundances of individual microbial taxa at different timepoints to fecal concentrations of calprotectin, a proxy for inflammation. Microbiome composition did not change over time as a result of the intervention, in terms of both alpha and beta diversity. However, before the intervention, the abundance of Haemophilus parainfluenzae was positively correlated with fecal calprotectin concentrations, and this correlation persisted in placebo-treated subjects throughout the study. In contrast, the correlation between H. parainfluenzae and calprotectin vanished in ACRE-treated subjects, while the relative abundance of H. parainfluenzae did not change. Our results suggest that ACRE treatment mitigates the contribution of H. parainfluenzae to inflammation. Further research is warranted to better comprehend the role of microbial composition in response to medical therapy including AC-rich extract in UC patients.<\/jats:p>","DOI":"10.3390\/microorganisms12112376","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:14:38Z","timestamp":1732094078000},"page":"2376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anthocyanin-Rich Extract Mitigates the Contribution of the Pathobiont Genus Haemophilus in Mild-to-Moderate Ulcerative Colitis Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7898-3178","authenticated-orcid":false,"given":"Yannik","family":"Zobrist","sequence":"first","affiliation":[{"name":"University of Zurich, 8006 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-5081","authenticated-orcid":false,"given":"Michael","family":"Doulberis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Department of Medicine, Zurich University Hospital, 8091 Zurich, Switzerland"},{"name":"Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland"},{"name":"Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0824-4125","authenticated-orcid":false,"given":"Luc","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Department of Medicine, Zurich University Hospital, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-166X","authenticated-orcid":false,"given":"Gabriel E.","family":"Leventhal","sequence":"additional","affiliation":[{"name":"PharmaBiome AG, 8952 Schlieren, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1733-9188","authenticated-orcid":false,"given":"Gerhard","family":"Rogler","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Department of Medicine, Zurich University Hospital, 8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide Incidence and Prevalence of Inflammatory Bowel Disease in the 21st Century: A Systematic Review of Population-Based Studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","article-title":"Ulcerative Colitis","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/ibd.20986","article-title":"Ulcerative Colitis: Correlation of the Rachmilewitz Endoscopic Activity Index with Fecal Calprotectin, Clinical Activity, C-Reactive Protein, and Blood Leukocytes","volume":"15","author":"Schoepfer","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_4","first-page":"5","article-title":"Efficacy of Ustekinumab in the Treatment of Patients with Crohn\u2019s Disease with Failure to Previous Conventional or Biologic Therapy: A Prospective Observational Real-Life Study","volume":"72","author":"Miranda","year":"2021","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1136\/gutjnl-2011-300613","article-title":"Role of Biological Therapy for Inflammatory Bowel Disease in Developing Countries","volume":"61","author":"Rogler","year":"2012","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ctim.2006.03.008","article-title":"Patterns of Complementary and Alternative Medicine (CAM) Use in Patients with Inflammatory Bowel Disease: Perceived Stress Is a Potential Indicator for CAM Use","volume":"15","author":"Langhorst","year":"2007","journal-title":"Complement. Ther. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.3748\/wjg.v29.i20.3048","article-title":"Hericium Erinaceus, a Medicinal Fungus with a Centuries-Old History: Evidence in Gastrointestinal Diseases","volume":"29","author":"Gravina","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85838","DOI":"10.18632\/oncotarget.20689","article-title":"Extracts from Hericium Erinaceus Relieve Inflammatory Bowel Disease by Regulating Immunity and Gut Microbiota","volume":"8","author":"Diling","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Benzie, I.F.F., and Wachtel-Galor, S. (2011). Chapter 4: Bilberry (Vaccinium myrtillus L.). Herbal Medicine: Biomolecular and Clinical Aspects, CRC Press\/Taylor & Francis. [2nd ed.].","DOI":"10.1201\/b10787"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev.food.080708.100754","article-title":"Anthocyanins: Natural Colorants with Health-Promoting Properties","volume":"1","author":"He","year":"2010","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00394-015-1083-y","article-title":"Consumption of Anthocyanin-Rich Cherry Juice for 12 Weeks Improves Memory and Cognition in Older Adults with Mild-to-Moderate Dementia","volume":"56","author":"Kent","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2100152","DOI":"10.1002\/mnfr.202100152","article-title":"Role of Gut Microbiota in the Anti-Colitic Effects of Anthocyanin-Containing Potatoes","volume":"65","author":"Li","year":"2021","journal-title":"Mol. Nutr. Food. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mo, J., Ni, J., Zhang, M., Xu, Y., Li, Y., Karim, N., and Chen, W. (2022). Mulberry Anthocyanins Ameliorate DSS-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Modulating Gut Microbiota. Antioxidants, 11.","DOI":"10.3390\/antiox11091674"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1080\/10408398.2018.1533517","article-title":"Metabolism of Anthocyanins and Consequent Effects on the Gut Microbiota","volume":"59","author":"Tian","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1039\/C5FO01228G","article-title":"Dietary Protocatechuic Acid Ameliorates Dextran Sulphate Sodium-Induced Ulcerative Colitis and Hepatotoxicity in Rats","volume":"7","author":"Farombi","year":"2016","journal-title":"Food Funct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1039\/C8FO01962B","article-title":"Bilberry Anthocyanin Extract Promotes Intestinal Barrier Function and Inhibits Digestive Enzyme Activity by Regulating the Gut Microbiota in Aging Rats","volume":"10","author":"Li","year":"2019","journal-title":"Food Funct."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/ibd\/izad024","article-title":"The Underappreciated Role of Secretory IgA in IBD","volume":"29","author":"Bamias","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hurst, R.D., Lyall, K.A., Wells, R.W., Sawyer, G.M., Lomiwes, D., Ngametua, N., and Hurst, S.M. (2020). Daily Consumption of an Anthocyanin-Rich Extract Made From New Zealand Blackcurrants for 5 Weeks Supports Exercise Recovery Through the Management of Oxidative Stress and Inflammation: A Randomized Placebo Controlled Pilot Study. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.00016"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Biedermann, L., Doulberis, M., Schreiner, P., Nielsen, O.H., The, F.O., Brand, S., Burk, S., Hruz, P., Juillerat, P., and Krieger-Gr\u00fcbel, C. (2024). A Multi-Center Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase IIa Study to Evaluate the Efficacy, Safety and Tolerability of an Anthocyanin Rich Extract (ACRE) in Patients with Ulcerative Colitis. medRxiv, medRxiv:2024.07.19.24310589.","DOI":"10.1101\/2024.07.19.24310589"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.crohns.2012.07.010","article-title":"Bilberry Ingestion Improves Disease Activity in Mild to Moderate Ulcerative Colitis\u2014An Open Pilot Study","volume":"7","author":"Biedermann","year":"2013","journal-title":"J. Crohns Colitis"},{"key":"ref_21","first-page":"14","article-title":"World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects","volume":"81","author":"Review","year":"2014","journal-title":"J. Am. Coll. Dent."},{"key":"ref_22","unstructured":"European Medicines Agency (EMA) (2018). Guideline Good Clinical Practice E6(R2), Committee for Human Medicinal Products."},{"key":"ref_23","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2016). Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry, CDER."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1093\/ibd\/zaa010.041","article-title":"P113 evaluation of the efficacy of tofacitinib in patients with ulcerative colitis utilizing the modified mayo score: Data from the octave program","volume":"26","author":"Sandborn","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/ibd.20520","article-title":"Use of the Noninvasive Components of the Mayo Score to Assess Clinical Response in Ulcerative Colitis","volume":"14","author":"Lewis","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_26","unstructured":"U\u2019Ren, J.M., and Arnold, A.E. (2017). Illumina MiSeq Dual-Barcoded Two-Step PCR Amplicon Sequencing Protocol. Protocols.io."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"giz107","DOI":"10.1093\/gigascience\/giz107","article-title":"A Field Guide for the Compositional Analysis of Any-Omics Data","volume":"8","author":"Quinn","year":"2019","journal-title":"Gigascience"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Haynes, W. (2013). Benjamini\u2013Hochberg Method. Encyclopedia of Systems Biology, Springer.","DOI":"10.1007\/978-1-4419-9863-7_1215"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Singh, A., Yau, Y.F., Leung, K.S., El-Nezami, H., and Lee, J.C.-Y. (2020). Interaction of Polyphenols as Antioxidant and Anti-Inflammatory Compounds in Brain\u2013Liver\u2013Gut Axis. Antioxidants, 9.","DOI":"10.3390\/antiox9080669"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/mnfr.201100380","article-title":"Bilberries and Their Anthocyanins Ameliorate Experimental Colitis","volume":"55","author":"Piberger","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100837","DOI":"10.1016\/j.nmni.2021.100837","article-title":"Oral Probiotics in Coronavirus Disease 2019: Connecting the Gut\u2013Lung Axis to Viral Pathogenesis, Inflammation, Secondary Infection and Clinical Trials","volume":"40","author":"Baindara","year":"2021","journal-title":"New Microbes New Infect."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Guo, Y., Yuan, W., Lyu, N., Pan, Y., Cao, X., Wang, Y., Han, Y., and Zhu, B. (2023). Association Studies on Gut and Lung Microbiomes in Patients with Lung Adenocarcinoma. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030546"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1039\/D1FO03376J","article-title":"Anti-Inflammatory and Intestinal Microbiota Modulation Properties of High Hydrostatic Pressure Treated Cyanidin-3-Glucoside and Blueberry Pectin Complexes on Dextran Sodium Sulfate-Induced Ulcerative Colitis Mice","volume":"13","author":"Tan","year":"2022","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Moon, H.J., Cha, Y.S., and Kim, K.A. (2023). Blackcurrant Alleviates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice. Foods, 12.","DOI":"10.3390\/foods12051073"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9606","DOI":"10.1039\/D3FO02953K","article-title":"Maize Near-Isogenic Lines with Enhanced Flavonoids Alleviated Dextran Sodium Sulfate-Induced Murine Colitis via Modulation of the Gut Microbiota","volume":"14","author":"Wu","year":"2023","journal-title":"Food Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The Treatment-Naive Microbiome in New-Onset Crohn\u2019s Disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41586-019-1237-9","article-title":"Multi-Omics of the Gut Microbial Ecosystem in Inflammatory Bowel Diseases","volume":"569","author":"Arze","year":"2019","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1093\/ecco-jcc\/jjz016","article-title":"The Microbiome in Paediatric Crohn\u2019s Disease\u2014A Longitudinal, Prospective, Single-Centre Study","volume":"13","author":"Kansal","year":"2019","journal-title":"J. Crohns Colitis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1097\/MEG.0000000000002050","article-title":"Fecal and Mucosal Microbiota Profiling in Pediatric Inflammatory Bowel Diseases","volume":"33","author":"Putignani","year":"2021","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.chom.2018.09.009","article-title":"Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course","volume":"24","author":"Schirmer","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2028366","DOI":"10.1080\/19490976.2022.2028366","article-title":"A Specific Microbiota Signature Is Associated to Various Degrees of Ulcerative Colitis as Assessed by a Machine Learning Approach","volume":"14","author":"Barberio","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2083419","DOI":"10.1080\/19490976.2022.2083419","article-title":"Gut Microbiota in Mucosa and Feces of Newly Diagnosed, Treatment-Na\u00efve Adult Inflammatory Bowel Disease and Irritable Bowel Syndrome Patients","volume":"14","author":"Panek","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.chom.2020.12.003","article-title":"Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease","volume":"29","author":"Shapiro","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/nri3322","article-title":"New Concepts in the Generation and Functions of IgA","volume":"12","author":"Pabst","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.coi.2011.07.010","article-title":"Pathobionts of the Gastrointestinal Microbiota and Inflammatory Disease","volume":"23","author":"Chow","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2014.08.006","article-title":"Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease","volume":"158","author":"Palm","year":"2014","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.cgh.2015.02.028","article-title":"Bridging the Gap between Host Immune Response and Intestinal Dysbiosis in Inflammatory Bowel Disease: Does Immunoglobulin a Mark the Spot?","volume":"13","author":"Shapiro","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1186\/s12967-018-1723-0","article-title":"Clinical Significance of Soluble Immunoglobulins A and G and Their Coated Bacteria in Feces of Patients with Inflammatory Bowel Disease","volume":"16","author":"Lin","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/imm.13091","article-title":"Gut IgA Abundance in Adult Life Is a Major Determinant of Resistance to Dextran Sodium Sulfate-Colitis and Can Compensate for the Effects of Inadequate Maternal IgA Received by Neonates","volume":"158","author":"Gupta","year":"2019","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, X., Wang, L., Zhuang, H., Yang, Z., Jiang, G., and Liu, Z. (2022). Promoting Intestinal IgA Production in Mice by Oral Administration with Anthocyanins. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.826597"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3164\/jcbn.15-15","article-title":"Dietary Polyphenols Increase Fecal Mucin and Immunoglobulin A and Ameliorate the Disturbance in Gut Microbiota Caused by a High Fat Diet","volume":"57","author":"Taira","year":"2015","journal-title":"J. Clin. Biochem. Nutr."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/11\/2376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:36:04Z","timestamp":1760114164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/11\/2376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":51,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["microorganisms12112376"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12112376","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}