{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:28:23Z","timestamp":1784042903445,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"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"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["UK\/US\/06\/2022\/01\/00004"],"award-info":[{"award-number":["UK\/US\/06\/2022\/01\/00004"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALAB Laboratories","award":["503\/6-006-05"],"award-info":[{"award-number":["503\/6-006-05"]}]},{"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: The gut microbiome is a key modulator of the gut\u2013brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan\/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map\u2122 Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites\u2014homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)\u2014were quantified using LC-MS\/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite\u2013symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance.<\/jats:p>","DOI":"10.3390\/nu17132232","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T02:53:07Z","timestamp":1751856787000},"page":"2232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessment of the Gut Microbiome in Patients with Coexisting Irritable Bowel Syndrome and Chronic Fatigue Syndrome"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2051-9873","authenticated-orcid":false,"given":"Marcin","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":"Aleksandra","family":"B\u0142o\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition and Gastroenterological Diagnostics, Medical University of Lodz, 90-647 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Kaczka","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\/0000-0003-0838-4208","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"}]},{"given":"Natalia","family":"Romanowska","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Medical University of Lodz, 92-213 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":"Pop\u0142awski","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":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e003973","DOI":"10.1136\/bmjopen-2013-003973","article-title":"Case definitions for chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME): A systematic review","volume":"4","author":"Brurberg","year":"2014","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s11011-019-0388-6","article-title":"Myalgic encephalomyelitis or chronic fatigue syndrome: How could the illness develop","volume":"34","author":"Morris","year":"2019","journal-title":"Metabol. Brain Dis."},{"key":"ref_3","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_4","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_5","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_6","unstructured":"Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome, and Board on the Health of Select Populations and Institute of Medicine (2015, February 10). Beyond Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Redefining an Illness, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK274235."},{"key":"ref_7","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 Neuroinflommaton in ME\/CFS snd Long COVID to Sustain Disease and Promote Relapses. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.877772"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nagy-Szakal, D., Williams, B.L., Mishra, N., Che, X., Lee, B., Bateman, L., Klimas, N.G., Komaroff, A.L., Levine, S., and Montoya, J.G. (2017). Fecal Metagenomic Profiles in Subgroups of Patients With Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Microbiome, 5.","DOI":"10.1186\/s40168-017-0261-y"},{"key":"ref_9","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_10","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_11","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_12","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_13","doi-asserted-by":"crossref","unstructured":"Lupo, G.F.D., Rocchetti, G., Lucini, L., Lorusso, L., Manara, E., Bertelli, M., Puglisi, E., and Capelli, E. (2021). Potential Role of Microbiome in Chronic Fatigue Syndrome\/Myalgic Encephalomyelits (CFS\/ME). Sci. Rep., 11.","DOI":"10.1038\/s41598-021-86425-6"},{"key":"ref_14","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_15","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_16","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_17","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_18","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_19","doi-asserted-by":"crossref","first-page":"e14621","DOI":"10.1111\/nmo.14621","article-title":"Intestinal bacteria associated with irritable bowel syndrome and chroni\u0107 fatigue syndrome","volume":"35","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Raij, T., and Raij, K. (2024). Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1358404"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gao, J., Xu, K., Liu, H., Liu, G., Bai, M., Peng, C., Li, T., and Yin, Y. (2018). Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00013"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial Tryptophan Catabolites in Health and Disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_24","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_25","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_26","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1128\/JVI.03678-13","article-title":"Epstein-Barr Virus Infection Induces Indoleamine 2,3-Dioxygenase Expression in Human Monocyte-Derived Macrophages Through P38\/Mitogen-Activated Protein Kinase and NF- B Pathways: Impairment in T Cell Functions","volume":"88","author":"Liu","year":"2014","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1023\/A:1013256629600","article-title":"Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel diseases","volume":"47","author":"Magro","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.brainres.2018.03.015","article-title":"Neurotransmitterr modulation by the gut microbiota","volume":"1693","author":"Strandwitz","year":"2018","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","article-title":"Indigenous Bactria of Gut Microbiota Regulate Serotonin Biosynthesis","volume":"161","author":"Yano","year":"2015","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7493","DOI":"10.3390\/ijms16047493","article-title":"Impact of gut bacteria on human health and diseases","volume":"16","author":"Zhang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","first-page":"5560310","article-title":"Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Napolitano, M., Fasulo, E., Ungaro, F., Massimino, L., Sinagra, E., Danese, S., and Mandarino, F.V. (2023). Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications. Microorganisms, 11.","DOI":"10.3390\/microorganisms11102369"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, M., Ruan, G., Chen, L., Ying, S., Li, G., Xu, F., Xiao, Z., Tian, Y., Lv, L., and Ping, Y. (2021). Naurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.817100"},{"key":"ref_34","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_35","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_36","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_37","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 erthematosus","volume":"46","author":"Krupp","year":"1989","journal-title":"Arch. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.14309\/ajg.0000000000000501","article-title":"ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth","volume":"115","author":"Pimentel","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.slsci.2015.10.001","article-title":"Sleep Quality and the Treatment of Intestinal Microbiota Imbalance in Chronic Fatigue Syndrome: A Pilot Study","volume":"8","author":"Jackson","year":"2015","journal-title":"Sleep Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shukla, S.K., Cook, D., Meyer, J., Vernon, S.D., Le, T., Clevidence, D., Robertson, C.E., Schrodi, S.J., Yale, S., and Frank, D.N. (2015). Changes in Gut and Plasma Microbiome Following Exercise Challenge in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145453"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1757-4749-5-3","article-title":"Intestinal Microbiota, Probiotics and Mental Health: From Metchnikoff to Modern Advances: Part II\u2014Contemporary Contextual Research","volume":"5","author":"Bested","year":"2013","journal-title":"Gut Pathog."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12967-017-1229-1","article-title":"Examining Clinical Similarities Between Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome and D-Lactic Acidosis: A Systematic Review","volume":"15","author":"Wallis","year":"2017","journal-title":"J Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.psyneuen.2018.11.032","article-title":"Persistent Fatigue Induced by Interferon-Alpha: A Novel, InflammationBased, Proxy Model of Chronic Fatigue Syndrome","volume":"100","author":"Russell","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nature25979","article-title":"Extensive Impact of Non-Antibiotic Drugs on Human Gut Bacteria","volume":"555","author":"Maier","year":"2018","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kenyon, J.N., Coe, S., and Izadi, H. (2019). A Retrospective Outcome Study of 42 Patients With Chronic Fatigue Syndrome, 30 of Whom had Irritable Bowel Syndrome. Half Were Treated With Oral Approaches, and Half Were Treated with Faecal Microbiome Transplantation. Hum. Microbiome J., 13.","DOI":"10.1016\/j.humic.2019.100061"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s12602-018-9397-8","article-title":"A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis (CFS\/ME)","volume":"10","author":"Corbitt","year":"2018","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chojnacki, J., Konrad, P., M\u0119drek-Socha, M., Kaczka, A., B\u0142o\u0144ska, A., Zajdel, R., Chojnacki, C., and G\u0105siorowska, A. (2023). The Variability of Tryptophan Metabolism in Patients With Mixed Type of Irritable Bowel Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms25052550"},{"key":"ref_49","first-page":"621","article-title":"Increased D-Lactic Acid Intestinal Bacteria in Patients With Chronic Fatigue Syndrome","volume":"23","author":"Sheedy","year":"2009","journal-title":"In Vivo"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12967-018-1392-z","article-title":"Open-Label Pilot for Treatment Targeting Gut Dysbiosis in Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome: Neuropsychological Symptoms and Sex Comparisons","volume":"16","author":"Wallis","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Giloteaux, L., Goodrich, J.K., Walters, W.A., Levine, S.M., Ley, R.E., and Hanson, M.R. (2016). Reduced Diversity and Altered Composition of the Gut Microbiome in Individuals With Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Microbiome, 4.","DOI":"10.1186\/s40168-016-0171-4"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"274S","DOI":"10.1093\/jn\/136.1.274S","article-title":"Branched-chain amino acids and central fatigue","volume":"136","author":"Newsholme","year":"2006","journal-title":"J. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"553S","DOI":"10.1093\/jn\/136.2.553S","article-title":"Exercise, serum free tryptophan, and central fatigue","volume":"136","author":"Fernstrom","year":"2006","journal-title":"J Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4137\/IJTR.S14084","article-title":"Tryptophan and kynurenic acid may produce an amplified effect in central fatigue induced by chronic sleep disorder","volume":"7","author":"Yamashita","year":"2014","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1017\/S031716710001266X","article-title":"Essential role of excessive tryptophan and its neurometabolites in fatigue","volume":"39","author":"Yamamoto","year":"2012","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.brainres.2017.09.002","article-title":"Tryptophan circuit in fatigue: From blood to brainand cognition","volume":"1675","author":"Yamashita","year":"2017","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e000254","DOI":"10.1136\/lupus-2017-000254","article-title":"Kynurenine pathway is altered in patients with SLE and associated with severe fatigue","volume":"5","author":"Pettersson","year":"2018","journal-title":"Lupus Sci. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2174\/1567202054368326","article-title":"Role of kynurenines in the central and peripheral nervous systems","volume":"2","author":"Toldi","year":"2005","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chojnacki, C., B\u0142o\u0144ska, A., Konrad, P., Chojnacki, M., Podogrocki, M., and Pop\u0142awski, M. (2023). Changes in Tryptophan Metabolism on serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome. Int. J. Mol. Sci., 15.","DOI":"10.3390\/nu15051262"},{"key":"ref_60","first-page":"104024","article-title":"Quinolinic acid: An endogenous neurotoxin with multiple target","volume":"2013","author":"Pineda","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1046\/j.0953-816x.2001.01592.x","article-title":"Presynaptic kynurenate-sensitive receptors inhibit glutamate release","volume":"13","author":"Carpenedo","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s12031-009-9235-2","article-title":"The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex","volume":"40","author":"Wu","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00787.2016","article-title":"Vasculopathy in the setting of cardiorenal syndrome: Roles of protein-bound uremic toxins","volume":"313","author":"Guo","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_64","first-page":"292","article-title":"Clinical applications of urinary organic acids. Part 2. Dysbiosis markers","volume":"13","author":"Lord","year":"2008","journal-title":"Altern. Med. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chong, P.P., Chin, V.K., Looi, C.Y., Wong, W.F., Madhavan, P., and Yong, V.C. (2019). The Microbiome and Irritable Bowel Syndrome\u2014A Review on the Pathology, Current Research and Future Therapy. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01136"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Jovanovic, F., Jovanovic, V., and Knezevic, N.N. (2023). Glucocoricoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions. Cells, 12.","DOI":"10.3390\/cells12081178"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"173363","DOI":"10.1016\/j.ejphar.2020.173363","article-title":"Experimental hypothyroidism raises brain kynurenic acid\u2014Novel aspect of thyroid dysfunction","volume":"883","author":"Tomczyk","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.bbi.2017.08.024","article-title":"Kynurenic acid is reduced in females and contraceptive users: Implications for depression","volume":"67","author":"Meier","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111890","DOI":"10.1016\/j.mad.2023.111890","article-title":"Relation of the kynurenine pathway with normal age: A systemic review","volume":"217","author":"Bakker","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"698","DOI":"10.14336\/AD.2021.0824","article-title":"The Role of Kynurenine Pathway and NAD+ Metabolsm in Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome","volume":"13","author":"Dehhaghi","year":"2022","journal-title":"Aging Dis."},{"key":"ref_71","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_72","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_73","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrn3071","article-title":"Gut Feelings: The Emerging Biology of Gut\u2013Brain Communication","volume":"12","author":"Mayer","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e270","DOI":"10.1002\/imt2.270","article-title":"Gut-X axis","volume":"4","author":"Lin","year":"2025","journal-title":"Imeta"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:05:12Z","timestamp":1760033112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":74,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["nu17132232"],"URL":"https:\/\/doi.org\/10.3390\/nu17132232","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,5]]}}}