{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:53:57Z","timestamp":1783727637452,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan (NRRP)","award":["3138"],"award-info":[{"award-number":["3138"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["3175"],"award-info":[{"award-number":["3175"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["1034"],"award-info":[{"award-number":["1034"]}]},{"name":"European Union\u2014NextGenerationEU","award":["3138"],"award-info":[{"award-number":["3138"]}]},{"name":"European Union\u2014NextGenerationEU","award":["3175"],"award-info":[{"award-number":["3175"]}]},{"name":"European Union\u2014NextGenerationEU","award":["1034"],"award-info":[{"award-number":["1034"]}]},{"name":"Italian Ministry of University and Research","award":["3138"],"award-info":[{"award-number":["3138"]}]},{"name":"Italian Ministry of University and Research","award":["3175"],"award-info":[{"award-number":["3175"]}]},{"name":"Italian Ministry of University and Research","award":["1034"],"award-info":[{"award-number":["1034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Fibromyalgia (FM) is a complex chronic syndrome characterized by widespread pain, fatigue, and gastrointestinal complaints. Clinical observations and preliminary metabolomic data suggest a possible link between symptom severity and intestinal dysbiosis, including fungal overgrowth. This study investigates whether a carb-free oloproteic diet can beneficially modulate the gut microbiota in FM patients. Thirty-four female patients with diagnosed FM were enrolled in a controlled, parallel-arm nutritional intervention. Group FM1 (n = 22) followed a 45-day carb-free oloproteic diet followed by a 45-day low-glycemic (LOGI) diet. Group FM2 (n = 12) received a continuous LOGI diet for 90 days. They were collected at baseline (T0), after 45 days (T45), and at 90 days (T90). Microbial profiles were analyzed by 16S and 18S rRNA gene sequencing to assess bacterial and fungal composition. In FM1, the oloproteic phase led to a marked reduction in fungal abundance (Ascomycota) and an increase in butyrate-producing bacteria such as Faecalibacterium and Roseburia. These changes were partially reversed after the LOGI phase. In FM2, no significant microbiota shifts were observed. Clinical improvements paralleled microbiota modulation only in FM1. The carb-free oloproteic diet may support gut microbial rebalancing in FM, particularly through transient suppression of fungal overgrowth. These findings support further investigation into nutritional strategies targeting dysbiosis in FM management.<\/jats:p>","DOI":"10.3390\/microorganisms13092069","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T12:18:18Z","timestamp":1757074698000},"page":"2069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of Gut Bacterial and Fungal Microbiota in Fibromyalgia Patients Following a Carb-Free Oloproteic Diet: Evidence for Candida Suppression and Symptom Improvement"],"prefix":"10.3390","volume":"13","author":[{"given":"Giuseppe","family":"Castaldo","sequence":"first","affiliation":[{"name":"NutriKeto_LAB Unisa, \u201cSan Giuseppe Moscati\u201d National Hospital (AORN), Contrada Amoretta, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5315-3055","authenticated-orcid":false,"given":"Maria","family":"D\u2019Elia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"},{"name":"Department of Earth and Marine Sciences, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3955-5675","authenticated-orcid":false,"given":"Mariagrazia","family":"De Prisco","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-9882","authenticated-orcid":false,"given":"Veronica","family":"Folliero","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"D\u2019Ursi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-4331","authenticated-orcid":false,"given":"Gianluigi","family":"Franci","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-5450","authenticated-orcid":false,"given":"Luca","family":"Rastrelli","sequence":"additional","affiliation":[{"name":"NutriKeto_LAB Unisa, \u201cSan Giuseppe Moscati\u201d National Hospital (AORN), Contrada Amoretta, 83100 Avellino, Italy"},{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Salerno, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1093\/rheumatology\/keaa847","article-title":"An Association between Chronic Widespread Pain and the Gut Microbiome","volume":"60","author":"Freidin","year":"2021","journal-title":"Rheumatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrrheum.2015.56","article-title":"The Role of Sleep in Pain and Fibromyalgia","volume":"11","author":"Choy","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Paola, R.D., Cuzzocrea, S., and Impellizzeri, D. (2021). Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083891"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jurado-Priego, L.N., Cueto-Ure\u00f1a, C., Ram\u00edrez-Exp\u00f3sito, M.J., and Mart\u00ednez-Martos, J.M. (2024). Fibromyalgia: A Review of the Pathophysiological Mechanisms and Multidisciplinary Treatment Strategies. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071543"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.5114\/reum\/201416","article-title":"Insights into Diagnosis and Treatment of Fibromyalgia among Moroccan Rheumatologists: A Cross Sectional Online Survey","volume":"63","author":"Imane","year":"2025","journal-title":"Reumatologia"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sultan, S., El-Mowafy, M., Elgaml, A., Ahmed, T.A.E., Hassan, H., and Mottawea, W. (2021). Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.715506"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in Health and Diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ogunrinola, G.A., Oyewale, J.O., Oshamika, O.O., and Olasehinde, G.I. (2020). The Human Microbiome and Its Impacts on Health. Int. J. Microbiol., 2020.","DOI":"10.1155\/2020\/8045646"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1224","DOI":"10.1097\/PR9.0000000000001224","article-title":"Decoding the Connection: Unraveling the Role of Gut Microbiome in Fibromyalgia","volume":"10","author":"Minerbi","year":"2025","journal-title":"Pain Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Erdrich, S., Hawrelak, J.A., Myers, S.P., Vuyisich, M., and Harnett, J.E. (2023). Investigating the Association between the Symptoms of Women with Fibromyalgia, Digestive Function, and Markers of the Microbiota of the Gastrointestinal Tract (The FIDGIT Study): Study Protocol. BMC Musculoskelet. Disord., 24.","DOI":"10.1186\/s12891-023-06259-3"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Laudes, M., Geisler, C., Rohmann, N., Bouwman, J., Pischon, T., and Schlicht, K. (2021). Microbiota in Health and Disease\u2014Potential Clinical Applications. Nutrients, 13.","DOI":"10.3390\/nu13113866"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12987-025-00644-x","article-title":"Hyphal Penetration Is the Major Pathway of Translocation of Candida Albicans across the Blood-Cerebrospinal Fluid Barrier","volume":"22","author":"Schmidt","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Morelli, M., and Queiroz, K. (2025). Breaking Barriers: Candidalysin Disrupts Epithelial Integrity and Induces Inflammation in a Gut-on-Chip Model. Toxins, 17.","DOI":"10.3390\/toxins17020089"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110183","DOI":"10.1016\/j.celrep.2021.110183","article-title":"Estrogen Promotes Innate Immune Evasion of Candida Albicans through Inactivation of the Alternative Complement System","volume":"38","author":"Kumwenda","year":"2022","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.nut.2017.07.004","article-title":"Low Fermentable, Oligo-, Di-, Mono-Saccharides and Polyol Diet in the Treatment of Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis","volume":"45","author":"Schumann","year":"2018","journal-title":"Nutrition"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Reddel, S., Putignani, L., and Del Chierico, F. (2019). The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions. Nutrients, 11.","DOI":"10.3390\/nu11020373"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sukkar, G., and Muscaritoli, M. (2021). Clinical Perspective of Low Carbohydrate Ketogenic Diets: A Narrative Review Samir. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.642628"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1550-2783-11-19","article-title":"The effects of consuming a high protein diet (4.4 g\/kg\/d) on body composition in resistance-trained individuals","volume":"11","author":"Antonio","year":"2014","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/ajcn\/87.3.621","article-title":"Weight-Loss Diet That Includes Consumption of Medium-Chain Triacylglycerol Oil Leads to a Greater Rate of Weight and Fat Mass Loss than Does Olive Oil","volume":"87","author":"Bosarge","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Comerford, K.B., Drewnowski, A., Papanikolaou, Y., Jones, J.M., Slavin, J., Angadi, S.S., and Rodriguez, J. (2023). Application of a New Carbohydrate Food Quality Scoring System: An Expert Panel Report. Nutrients, 15.","DOI":"10.3390\/nu15051288"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Orengo, S.L.D., Vilhena Da Silva, R.D.C., Macarini, A.F., Cechinel Filho, V., and De Souza, P. (2025). Prolonged Diuretic, Natriuretic, and Potassium- and Calcium-Sparing Effect of Hesperidin in Hypertensive Rats. Plants, 14.","DOI":"10.3390\/plants14091324"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1089\/acm.2017.0083","article-title":"Therapeutic Uses of Triphala in Ayurvedic Medicine","volume":"23","author":"Peterson","year":"2017","journal-title":"J. Altern. Complement. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Castaldo, G., Marino, C., D\u2019Elia, M., Grimaldi, M., Napolitano, E., D\u2019Ursi, A.M., and Rastrelli, L. (2024). The Effectiveness of the Low-Glycemic and Insulinemic (LOGI) Regimen in Maintaining the Benefits of the VLCKD in Fibromyalgia Patients. Nutrients, 16.","DOI":"10.3390\/nu16234161"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ni, C., Jia, Q., Ding, G., Wu, X., and Yang, M. (2022). Low-Glycemic Index Diets as an Intervention in Metabolic Diseases: A Systematic Review and Meta-Analysis. Nutrients, 14.","DOI":"10.3390\/nu14020307"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s42000-024-00566-7","article-title":"The Role of Low Glycemic Index and Load Diets in Medical Nutrition Therapy for Type 2 Diabetes: An Update","volume":"23","author":"Gerontiti","year":"2024","journal-title":"Hormones"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pacciani-Mori, L., Giometto, A., Suweis, S., and Maritan, A. (2020). Dynamic Metabolic Adaptation Can Promote Species Coexistence in Competitive Microbial Communities. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1007896"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fusco, W., Lorenzo, M.B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M.C., Gasbarrini, A., and Collado, M.C. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15092211"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11739-023-03374-w","article-title":"Gut Microbiota, Intestinal Permeability, and Systemic Inflammation: A Narrative Review","volume":"19","author":"Petito","year":"2024","journal-title":"Intern. Emerg. Med."},{"key":"ref_29","first-page":"326","article-title":"The Ketogenic Diet: Its Impact on Human Gut Microbiota and Potential Consequent Health Outcomes: A Systematic Literature Review","volume":"15","author":"Rew","year":"2022","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Chen, Y., Chen, Y., Gong, X., Chen, Z., and Zhang, X. (2025). Ketogenic Diet and Gut Microbiota: Exploring New Perspectives on Cognition and Mood. Foods, 14.","DOI":"10.3390\/foods14071215"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Theis, B.F., Park, J.S., Kim, J.S.A., Zeydabadinejad, S., Vijay-Kumar, M., Yeoh, B.S., and Saha, P. (2025). Gut Feelings: How Microbes, Diet, and Host Immunity Shape Disease. Biomedicines, 13.","DOI":"10.3390\/biomedicines13061357"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/ajcn\/nqx042","article-title":"The Effect of Dietary Glycemic Index and Glycemic Load on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Clinical Trials","volume":"107","author":"Milajerdi","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Talapko, J., Juzba\u0161i\u0107, M., Matijevi\u0107, T., Pustijanac, E., Beki\u0107, S., Kotris, I., and \u0160krlec, I. (2021). Candida Albicans-The Virulence Factors and Clinical Manifestations of Infection. J. Fungi, 7.","DOI":"10.3390\/jof7020079"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Oliveira-Pacheco, J., Alves, R., Costa-Barbosa, A., Cerqueira-Rodrigues, B., Pereira-Silva, P., Paiva, S., Silva, S., Henriques, M., Pais, C., and Sampaio, P. (2018). The Role of Candida Albicans Transcription Factor RLM1 in Response to Carbon Adaptation. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01127"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2399360","DOI":"10.1080\/19490976.2024.2399360","article-title":"Effect of Diet on the Gut Mycobiome and Potential Implications in Inflammatory Bowel Disease","volume":"16","author":"Buttar","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nri.2017.55","article-title":"Fungal Dysbiosis: Immunity and Interactions at Mucosal Barriers","volume":"17","author":"Iliev","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Al-Dujaili, E.A.S., Ashmore, S., and Tsang, C. (2019). A Short Study Exploring the Effect of the Glycaemic Index of the Diet on Energy Intake and Salivary Steroid Hormones. Nutrients, 11.","DOI":"10.3390\/nu11020260"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yu, D., Xie, L., Chen, W., Qin, J., Zhang, J., Lei, M., Wang, Y., Tang, H., Xue, S., and Liang, X. (2022). Dynamics of the Gut Bacteria and Fungi Accompanying Low-Carbohydrate Diet-Induced Weight Loss in Overweight and Obese Adults. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.846378"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00038-21","DOI":"10.1128\/AEM.00038-21","article-title":"The Nutritional Significance of Intestinal Fungi: Alteration of Dietary Carbohydrate Composition Triggers Colonic Fungal Community Shifts in a Pig Model","volume":"87","author":"Luo","year":"2021","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40101-014-0040-4","article-title":"Natural Environments, Ancestral Diets, and Microbial Ecology: Is There a Modern \u201cPaleo-Deficit Disorder\u201d? Part II","volume":"34","author":"Logan","year":"2015","journal-title":"J. Physiol. Anthropol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Matija\u0161i\u0107, M., Me\u0161trovi\u0107, T., Paljetak, H.\u010c., Peri\u0107, M., Bare\u0161i\u0107, A., and Verbanac, D. (2020). Gut Microbiota beyond Bacteria-Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082668"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yoo, J.Y., Groer, M., Dutra, S.V.O., Sarkar, A., and McSkimming, D.I. (2020). Gut Microbiota and Immune System Interactions. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101587"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dmytriv, T.R., Storey, K.B., and Lushchak, V.I. (2024). Intestinal Barrier Permeability: The Influence of Gut Microbiota, Nutrition, and Exercise. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1380713"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/2069\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:40:12Z","timestamp":1760035212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/9\/2069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["microorganisms13092069"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13092069","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]}}}