{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:16:14Z","timestamp":1784002574732,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/6-006-05"],"award-info":[{"award-number":["503\/6-006-05"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALAB Laboratories","award":["UK\/US\/06\/2022\/01\/00004"],"award-info":[{"award-number":["UK\/US\/06\/2022\/01\/00004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Gut dysbiosis in Chronic Fatigue Syndrome (CFS) drives low-grade inflammation and shifts tryptophan metabolism toward neurotoxic pathways. The causal link between bacterial translocation, kynurenine pathway dysregulation, and symptom severity remains under-defined. We evaluated the impact of a high-concentration multi-strain probiotic on the \u201cgut-kynurenine axis\u201d and clinical status in CFS patients with co-morbid IBS-U and confirmed dysbiosis. Methods: Forty female patients with confirmed dysbiosis (GA-map\u2122 Dysbiosis Index &gt; 2) received the CDS22 formula (450 billion CFU\/day) for 12 weeks. We compared urinary tryptophan metabolite profiles (LC-MS\/MS), gut dysbiosis markers (3-indoxyl sulfate), and fatigue severity (FSS) against 40 age-matched healthy controls. Results: Baseline analysis revealed profound metabolic perturbations: elevated bacterial proteolytic markers (3-IS), substrate depletion (low tryptophan), and a neurotoxic signature (high quinolinic acid [QA], low kynurenic acid [KYNA]). Following the intervention, fatigue scores declined by 40.3%, with 97.5% of patients reaching the remission threshold (FSS &lt; 36). Biochemically, 3-IS levels decreased to the range observed in healthy controls and attenuated xanthurenic acid levels. Although absolute QA concentrations remained elevated compared to controls, the neuroprotective KYNA\/QA ratio increased significantly (+45%). Increased systemic tryptophan availability correlated directly with clinical symptom reduction (Spearman\u2019s rho = \u22120.36, p = 0.024). Conclusions: The CDS22 formulation was associated with a restoration of intestinal eubiosis and functional tryptophan partitioning. Clinical remission coincides with a metabolic shift favoring neuroprotection (increased KYNA\/QA ratio), validating the gut\u2013kynurenine axis as a modifiable therapeutic target. Peripheral metabolic improvement relative to the healthy baseline appeared sufficient for symptom relief in this specific phenotype, despite incomplete clearance of neurotoxic metabolites.<\/jats:p>","DOI":"10.3390\/nu18010174","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-Strain Probiotic Improves Tryptophan Metabolism and Symptoms in Chronic Fatigue Syndrome Patients with Co-Occurring Irritable Bowel Syndrome: An Open-Label Pilot Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-4775","authenticated-orcid":false,"given":"Cezary","family":"Chojnacki","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"M\u0119drek-Socha","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-7868","authenticated-orcid":false,"given":"Jan","family":"Chojnacki","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-3721","authenticated-orcid":false,"given":"Anita","family":"G\u0105siorowska","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-4208","authenticated-orcid":false,"given":"Ewa","family":"Walecka-Kapica","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-4097","authenticated-orcid":false,"given":"Michal","family":"Bijak","sequence":"additional","affiliation":[{"name":"Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Przybylowska-Sygut","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-7339","authenticated-orcid":false,"given":"Tomasz","family":"Poplawski","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.7326\/0003-4819-108-3-387","article-title":"Chronic Fatigue Syndrome: A Working Case Definition","volume":"108","author":"Holmes","year":"1988","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","article-title":"The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study","volume":"121","author":"Fukuda","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1300\/J092v11n01_02","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols","volume":"11","author":"Carruthers","year":"2003","journal-title":"J. Chronic Fatigue Syndr."},{"key":"ref_4","unstructured":"Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome, Board on the Health of Select Populations, and Institute of Medicine (2025, February 10). Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Redefining an Illness, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK274235\/."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tate, W., Walker, M., Sweetan, E., Heliweli, A., Peppercorn, K., Edgar, C., Blair, A., and Chatterjee, A. (2022). Molecular Mechanism of Neuroinflammation in ME\/CFS and Long COVID to Sustain Disease and Promote Relapses. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.877772"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40168-017-0261-y","article-title":"Fecal Metagenomic Profiles in Subgroups of Patients with Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"5","author":"Williams","year":"2017","journal-title":"Microbiome"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.anaerobe.2013.06.002","article-title":"High-Throughput 16S rRNA Gene Sequencing Reveals Alterations of Intestinal Microbiota in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Patients","volume":"22","author":"Fremont","year":"2013","journal-title":"Anaerobe"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11306-016-1145-z","article-title":"The Association of Fecal Microbiota and Fecal, Blood Serum and Urine Metabolites in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","volume":"13","author":"Armstrong","year":"2017","journal-title":"Metabolomics"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Navaneetharaja, N., Griffiths, V., Wileman, T., and Carding, S. (2016). A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)?. J. Clin. Med., 5.","DOI":"10.3390\/jcm5060055"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jad.2006.08.021","article-title":"Increased Serum IgA and IgM Against LPS of Enterobacteria in Chronic Fatigue Syndrome (CFS): Indication for the Involvement of Gram-Negative Enterobacteria in the Etiology of CFS and for the Presence of an Increased Gut\u2013Intestinal Permeability","volume":"99","author":"Maes","year":"2007","journal-title":"J. Affect. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7043","DOI":"10.1038\/s41598-021-86425-6","article-title":"Potential Role of Microbiome in Chronic Fatigue Syndrome\/Myalgic Encephalomyelits (CFS\/ME)","volume":"11","author":"Lupo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1042\/BIO03902010","article-title":"The Gut Microbiome in Myalgic Encephalomyelitis","volume":"39","author":"Hanson","year":"2017","journal-title":"Biochemist"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.jad.2011.09.010","article-title":"Increased IgA Responses to the LPS of Commensal Bacteria Is Associated with Inflammation and Activation of Cell-Mediated Immunity in Chronic Fatigue Syndrome","volume":"136","author":"Maes","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S136","DOI":"10.1093\/clinids\/18.Supplement_1.S136","article-title":"Immunologic Abnormalities Associated with Chronic Fatigue Syndrome","volume":"18","author":"Barker","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1743-7075-7-79","article-title":"Gut Inflammation in Chronic Fatigue Syndrome","volume":"7","author":"Lakhan","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"109648","DOI":"10.1016\/j.mehy.2020.109648","article-title":"From IBS to ME\u2014The Dysbiotic March Hypothesis","volume":"140","author":"Berstad","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14621","DOI":"10.1111\/nmo.14621","article-title":"Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue syndrome","volume":"35","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16228","DOI":"10.1038\/nmicrobiol.2016.228","article-title":"Dysbiosis is not an answer","volume":"1","author":"Olesen","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1093\/ajcn\/23.11.1433","article-title":"Human normal and abnormal gastrointestinal flora","volume":"23","author":"Haenel","year":"1970","journal-title":"J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.humic.2017.05.004","article-title":"History of medicine: Origin of the term microbiome why it matters","volume":"4","author":"Prescottt","year":"2017","journal-title":"Hum. Microbiome J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1111\/cmi.12308","article-title":"Defining dysbiosis and its influence on host immunity and disease","volume":"16","author":"Petersen","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1089\/jmf.2014.7000","article-title":"The Gut Microbiome and the Brain","volume":"17","author":"Galland","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chojnacki, M., B\u01420\u0144ska, A., Kaczka, A., Chojnacki, J., Walecka-Kapica, E., Romanowska, N., Przyby\u0142owska-Sygut, K., and Pop\u0142awski, T. (2025). Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome. Nutrients, 17.","DOI":"10.3390\/nu17132232"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1475-2891-8-4","article-title":"Effect of Supplement with Lactic-Acid Producing Bacteria on Fatigue and Physical Activity in Patients with Chronic Fatigue Syndrome","volume":"8","author":"Sullivan","year":"2009","journal-title":"Nutr. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/19490976.2017.1345414","article-title":"Using Probiotics in Clinical Practice: Where Are We Now? A Review of Existing Meta-Analyses","volume":"8","author":"Rondanelli","year":"2017","journal-title":"Gut Microbes"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lacy, B.E., and Patel, N.K. (2017). Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. J. Clin. Med., 6.","DOI":"10.3390\/jcm6110099"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/ajg.2011.358","article-title":"Patients Show Frequent Fluctuations between Loose\/Watery andHard\/Lumpy Stools: Implications for treatment","volume":"107","author":"Palsson","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0022-3999(93)90081-P","article-title":"Development of fatigue scale","volume":"37","author":"Chalder","year":"1993","journal-title":"J. Psychosom. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/archneur.1989.00520460115022","article-title":"The fatigue severity scale: Application to patients with multiple sclerosis and systemic lupus erythematosus","volume":"46","author":"Krupp","year":"1989","journal-title":"Arch. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/apt.13236","article-title":"Deviations in human gut microbiota: A novel diagnostic test for determining dysbiosis in patients with IBS or IBD","volume":"42","author":"Vebo","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nacul, L., Authier, F.J., Scheibenbogen, C., Lorusso, L., Helland, I.B., Martin, J.A., Sirbu, C.A., Mengshoel, A.M., Polo, O., and Behrends, U. (2021). European Network on Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME\/CFS in Europe. Medicina, 57.","DOI":"10.3390\/medicina57050510"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.clinthera.2016.04.038","article-title":"A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis","volume":"38","author":"Collatz","year":"2016","journal-title":"Clin. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kashi, A.A., Davis, R.W., and Phair, R.D. (2019). The IDO Metabolic Trap Hypothesis for the Etiology of ME\/CFS. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030082"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/s41591-018-0060-4","article-title":"Genetic Deficiency of Indoleamine 2,3-Dioxygenase Promotes Gut Microbiota-Mediated Metabolic Health","volume":"24","author":"Laurans","year":"2018","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22021","DOI":"10.1074\/jbc.M603503200","article-title":"Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wirthgen, E., Hoeflich, A., Rebi, A., and G\u03cbnther, J. (2018). Kynurenic acid: The Janus-faced role of an immunomodulatory tryptophan metabolite and its link to pathological conditions. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01957"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/ars.2017.7269","article-title":"Role of nicotinamide adenine dinucleotide and related precursors as therapeutic targets for age-related degenerative diseases: Rationale, biochemistry, pharmacokinetics, and outcomes","volume":"30","author":"Braidy","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3177\/jnsv.60.255","article-title":"Time-dependent effects of L-tryptophan administration on urinary excretion of L-tryptophan metabolites","volume":"60","author":"Hiratsuka","year":"2014","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Poesen, R., Mutsaers, H.A.M., Windey, K., Broek, P.H.v.D., Verweij, V., Augustijns, P., Kuypers, D., Jansen, J., Evenepoel, P., and Verbeke, K. (2015). The influence of dietary protein intake on mammalian tryptophan and phenolic metabolites. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140820"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0026-0495(73)90267-9","article-title":"Urinary excretion of quinolinic acid and other tryptophan metabolites after deoxypyridoxine or oral contraceptive administration","volume":"22","author":"Rose","year":"1973","journal-title":"Metabolism"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:35:51Z","timestamp":1767627351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18010174"],"URL":"https:\/\/doi.org\/10.3390\/nu18010174","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]}}}